Current Gene Therapy[JOURNAL]
Sun
200 papers
Identification of Gene Signatures Associated with COVID-19 across Children, Adolescents, and Adults in the Nasopharynx and Peripheral Blood by Using a Machine Learning Approach.
Bao Y, Ren J, Chen L … +4 more , Guo W, Feng K, Huang T, Cai YD
Curr Gene Ther · 2025 · PMID 39350407 · Publisher ↗
BACKGROUND: Significant variations in immune profiles across different age groups manifest distinct clinical symptoms and prognoses in Coronavirus Disease 2019 (COVID-19) patients. Predominantly, severe COVID-19 cases th...
BACKGROUND: Significant variations in immune profiles across different age groups manifest distinct clinical symptoms and prognoses in Coronavirus Disease 2019 (COVID-19) patients. Predominantly, severe COVID-19 cases that require hospitalization occur in the elderly, with the risk of severe illness escalating with age among young adults, children, and adolescents. OBJECTIVE: This study aimed to delineate the unique immune characteristics of COVID-19 across various age groups and evaluate the feasibility of detecting COVID-19-induced immune alterations through peripheral blood analysis. METHODS: By employing a machine learning approach, we analyzed gene expression data from nasopharyngeal and peripheral blood samples of COVID-19 patients across different age brackets. Nasopharyngeal data reflected the immune response to COVID-19 in the upper respiratory tract, while peripheral blood samples provided insights into the overall immune system status. Both datasets encompassed COVID-19 patients and healthy controls, with patients divided into children, adolescents, and adult age groups. The analysis included the expression levels of 62,703 genes per patient. Then, 9 feature-sequencing methods (least absolute shrinkage and selection operator, light gradient boosting machine, Monte Carlo feature selection, random forest, ridge regression, adaptive boosting, categorical boosting, extremely randomized trees, and extreme gradient boosting) were employed to evaluate the association of the genes with COVID-19. Key genes were then utilized to develop efficient classification models. RESULTS: The findings identified specific markers: insulin-like growth factor binding protein 3 (downregulated in the peripheral blood of COVID-19 patients), interferon alpha-inducible protein 27 (upregulated), and SERPING1 (upregulated in nasopharyngeal tissues). In addition, fibulin-2 was downregulated in adolescent patients, but upregulated in the other groups, while epoxide hydrolase 3 was upregulated in healthy controls, but downregulated in children and adolescents. CONCLUSION: This study offers valuable insights into the local and systemic immune responses of COVID-19 patients across age groups, aiding in identifying potential therapeutic targets and formulating personalized treatment strategies.
Pan-Cancer Single-Cell Analysis Revealing the Heterogeneity of Cancer- Associated Fibroblasts in Skin Tumors.
Zhang Y, Zhao Z, Huang W … +8 more , Kim BS, Lin L, Li X, Hou M, Li L, Zhang Y, Xi W, Chai G
Curr Gene Ther · 2025 · PMID 39323331 · Publisher ↗
BACKGROUND: Cancer-Associated Fibroblasts (CAFs) constitute a heterogeneous group of cells critical for the remodeling of the tumor microenvironment (TME). Given their significant impact on tumor progression, particularl...
BACKGROUND: Cancer-Associated Fibroblasts (CAFs) constitute a heterogeneous group of cells critical for the remodeling of the tumor microenvironment (TME). Given their significant impact on tumor progression, particularly in skin cancers, a deeper understanding of their characteristics and functions is essential. METHODS: This study employed a single-cell transcriptomic analysis to explore the diversity of CAFs within three major types of skin cancer: basal cell carcinoma, melanoma, and head and neck squamous cell carcinoma. We applied analytical techniques, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), pseudotime tracking, metabolic profiling, and stemness assessment to delineate and define the functional attributes of identified CAF subgroups. RESULTS: Our analysis successfully delineated nine distinct CAF subgroups across the studied tumor types. Of particular interest, we identified a novel CAF subtype, designated as C0, exclusive to basal cell carcinoma. This subtype exhibits phenotypic traits associated with invasive and destructive capabilities, significantly correlating with the progression of basal cell carcinoma. The identification of this subgroup provides new insights into the role of CAFs in cancer biology and opens avenues for targeted therapeutic strategies. CONCLUSION: A pan-cancer analysis was performed on three cancers, BCC, MA, and HNSCC, focusing on tumor fibroblasts in TME. Unsupervised clustering categorized CAF into nine subpopulations, among which the C0 subpopulation had a strong correspondence with BCC-CAF and an invasive- destructive-related phenotype.
Target and Gene-Based Therapeutic Strategies against Pancreatic Cancer: Current and Future Prospects.
Dwivedi M, Sanyal S, Singh S … +2 more , Dwivedi M, Sanyal S
Curr Gene Ther · 2025 · PMID 39318213 · Publisher ↗
Despite tremendous advancements in knowledge, diagnosis, and availability of both traditional and innovative treatments, pancreatic cancer remains a dangerous disease with a high death rate and dismal prognosis. The trad...
Despite tremendous advancements in knowledge, diagnosis, and availability of both traditional and innovative treatments, pancreatic cancer remains a dangerous disease with a high death rate and dismal prognosis. The traditional strategy in adjuvant and palliative settings is still cytotoxic chemotherapy predicated on the purine derivative gemcitabine; nevertheless, there is an increasing need for new medicines that target the primary molecular pathways and pathophysiological abnormalities implicated. There is now just a tiny amount of evidence of therapeutic benefit when the targeted drug erlotinib is added to the conventional gemcitabine treatment. In preclinical and clinical trials, novel medications targeting mTOR, NF-κB, and proteasome, including the enzyme histone deacetylase, are currently being studied alongside the well-established monoclonal antibody treatments and small-molecule protein tyrosine kinase inhibitors. These novel medications may change the negative natural progression of this illness in conjunction with gene therapy and immunotherapy, both of which are undergoing clinical study. In this regard, leveraging miRNA manipulation to combat cancer is appealing due to its promise to deliver personalized treatment tailored to an individual's distinct gene or miRNA expression profile. Preclinical studies involving animals have showcased the effectiveness of miRNA-based therapies, with several of these treatments now progressing into human clinical trials for various malignancies and other medical conditions. This review describes the important developments of targeted therapeutics that are associated with pancreatic cancer and the discoveries which can help in dealing with this fatal malignancy in a more significant manner.
Characteristics of Oxidative Phosphorylation-Related Subtypes and Construction of a Prognostic Signature in Ovarian Cancer.
Lu J, Zhen S, Li X
Curr Gene Ther · 2025 · PMID 39289931 · Publisher ↗
BACKGROUND: Ovarian cancer is associated with a high mortality rate. Oxidative Phosphorylation (OXPHOS) is an active metabolic pathway in cancer; nevertheless, its role in ovarian cancer continues to be ambiguous. Theref...
BACKGROUND: Ovarian cancer is associated with a high mortality rate. Oxidative Phosphorylation (OXPHOS) is an active metabolic pathway in cancer; nevertheless, its role in ovarian cancer continues to be ambiguous. Therefore, the objective of this study was to identify the prognostic value of OXPHOS-related genes and the immune landscape in ovarian cancer. METHODS: We obtained public ovarian cancer-related datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and recognized OXPHOS-related genes from the GeneCards database and literature. Cox regression analyses were conducted to identify prognostic OXPHOS-related genes and develop a prognostic nomogram based on the OXPHOS score and clinicopathological features of patients. Functional enrichment analyses were employed to identify related processes. RESULTS: A 12-gene signature was identified to classify the ovarian cancer patients into high- and low-risk groups. The Immunophenoscore (IPS) was higher in the OXPHOS score-high group than in the OXPHOS score-low group, suggesting a better response to immune checkpoint inhibitors. Functional enrichment analyses unveiled that OXPHOS-related genes were considerably abundant in a series of immune processes. The calibration curves of the constructed prognostic nomograms at 1, 2, and 3 years exhibited strong concordance between the anticipated and observed survival probabilities of ovarian cancer patients. CONCLUSION: We have constructed a prognostic model containing 12 OXPHOS-related genes and demonstrated its strong predictive value in ovarian cancer patients. OXPHOS has been found to be closely linked to immune infiltration and the reaction to immunotherapy, which may contribute to improving individualized treatment and prognostic evaluation in ovarian cancer.
DeepLCRmiRNA: A Hybrid Neural Network Approach for Identifying Lung Cancer-Associated miRNAs.
Cheng N, Chen C, Liu J … +4 more , Wang X, Gao Z, Mao M, Huang J
Curr Gene Ther · 2025 · PMID 39279703 · Publisher ↗
INTRODUCTION: Lung cancer stands as one of the most prevalent malignant neoplasms, with microRNAs (miRNAs) playing a pivotal role in the modulation of gene expression, impacting cancer cell proliferation, invasion, metas...
INTRODUCTION: Lung cancer stands as one of the most prevalent malignant neoplasms, with microRNAs (miRNAs) playing a pivotal role in the modulation of gene expression, impacting cancer cell proliferation, invasion, metastasis, immune escape, and resistance to therapy. METHODS: The intricate role of miRNAs in lung cancer underscores their significance as biomarkers for early detection and as novel targets for therapeutic intervention. Traditional approaches for the identification of miRNAs related to lung cancer, however, are impeded by inefficiencies and complexities. RESULTS: In response to these challenges, this study introduced an innovative deep-learning strategy designed for the efficient and precise identification of lung cancer-associated miRNAs. Through comprehensive benchmark tests, our method exhibited superior performance relative to existing technologies. CONCLUSION: Further case studies have also confirmed the ability of our model to identify lung cancer- associated miRNAs that have undergone biological validation.
Proteogenomic Identification and Analysis of KIF5B as a Prognostic Signature for Hepatocellular Carcinoma.
Qi L, Tan Y, Zhou Y … +5 more , Dong Y, Yang X, Chang S, Yu L, Liu D
Curr Gene Ther · 2025 · PMID 39248070 · Publisher ↗
BACKGROUND: Metabolic disorders are significant risk factors for liver cancer, particularly Hepatocellular Carcinoma (HCC). However, the molecular genetic basis of metabolic reprogramming in the liver remains largely unc...
BACKGROUND: Metabolic disorders are significant risk factors for liver cancer, particularly Hepatocellular Carcinoma (HCC). However, the molecular genetic basis of metabolic reprogramming in the liver remains largely uncertain. OBJECTIVE: This study aimed to investigate some novel prognostic biomarkers in HCC by using proteogenomic and transcriptomic analysis and explore the potential role of specific prognostic genes in HCC. METHODS: Here, we have presented a proteogenomic analysis of 10 pairs of HCC. Protein co-expression and pathway analysis were performed to investigate the biological characteristics of HCC. Protein and mRNA expression profiles of multi-cohorts were integrated to detect novel prognostic protein markers of HCC. The carcinogenic roles of candidate prognostic markers were further evaluated by MTS assay, colony formation, monolayer wound healing assay, and xenograft models. RESULTS: A total of 2086 proteins with significantly different expressions were detected in HCC. Pathways related to oncogenic signaling and insulin-related metabolism have been found to be dysregulated and differentially regulated in HCC. We have identified the novel prognostic biomarkers, KIF5B, involved in liver metabolic reprogramming. The biomarkers were identified using multivariable COX regression analysis from two independent proteomic datasets (Fudan Cohort and our recruited cohort) and the TCGA mRNA database. Both the protein and mRNA up-regulation of KIF5B have been found to be associated with a poor clinical outcome in HCC. Insulin activated the protein expression of KIF5B in HCC. Knocking out KIF5B expression by sgRNA decreased the protein expression of FASN and SCD1 and the intracellular triglyceride concentration. Silencing KIF5B suppressed HCC cell proliferation and colony formation in vitro, as well as HCC growth in xenograft models. CONCLUSION: Our findings have suggested KIF5B protein to function as a novel prognostic biomarker in HCC. KIF5B expression has been found to activate the AKT/mTOR pathway and reprogram triglyceride metabolism, leading to HCC development. Targeting KIF5B may be an effective strategy in the clinical treatment of HCC.
Delivery of Superoxide Dismutase 3 Gene with Baculoviruses Inhibits TNF-α Triggers Vascular Smooth Muscle Cell Proliferation and Inflammation.
Lin SL, Lee ST, Huang SE … +4 more , Chang TH, Geng YJ, Sulistyowati E, Yeh JL
Curr Gene Ther · 2025 · PMID 39238393 · Publisher ↗
BACKGROUND: Superoxide dismutase 3 (SOD3), recognized as a potent free radical scavenger, exhibits antioxidant, anti-inflammatory, and anti-angiogenic properties. However, the molecular mechanisms underlying the protecti...
BACKGROUND: Superoxide dismutase 3 (SOD3), recognized as a potent free radical scavenger, exhibits antioxidant, anti-inflammatory, and anti-angiogenic properties. However, the molecular mechanisms underlying the protective effects of SOD3 on the vascular smooth muscle cell during atherosclerosis remain unclear. OBJECTIVES: This study aimed to investigate the efficacy of the baculovirus expressing SOD3 gene delivery to vascular smooth muscle cells (VSMCs) and investigate whether the overexpression of SOD3 mitigates cell proliferation and migration induced by tumor necrosis factor-α (TNF-α). METHODS: A baculoviral vector containing SOD3 cDNA (vAcMBac-CMV-IE-SOD3) was constructed and utilized to deliver the SOD3 gene into primary rat VSMCs. Cells were stimulated with recombinant TNF-α, and then cell proliferation and migration were evaluated using the bromodeoxyuridine and wound healing assay. Western blot was used to verify the expression of cell cycle regulators, cellular mediators, and proliferative biomarkers. Zymography, immunofluorescence staining, and ELISA assay were conducted to assess the expression levels of matrix metalloproteinases. RESULTS: The results demonstrated efficient and non-cytotoxic transduction of vAcMBac- CMV-IE-SOD3 in VSMCs. SOD3 overexpression significantly suppressed cell proliferation and motility by inhibiting cell cycle regulators in TNF-α-induced cells. TNF-α elevated protein levels of phospho-ERK and phospho-Akt were reduced markedly by SOD3-overexpressing. Additionally, SOD3 overexpression attenuated the elevation of MMP-2 and MMP-9, the pro-inflammatory and proliferative biomarkers. Overall, the SOD3 gene delivery exhibited potent anti-proliferation and anti-inflammation effects on TNF-α-induced VSMCs. CONCLUSION: An effective SOD3 gene delivery using a recombinant baculoviral vector has been successfully established and is useful for overexpression of the SOD gene family. This approach provides new therapeutic strategies in gene therapy against atherosclerosis.
Recent Advances in Therapeutics and Manufacturing Processes of Recombinant Adeno-Associated Virus for the Treatment of Lung Diseases.
Sorroza-Martinez L, Pelletier M, Guay D … +1 more , Gaillet B
Curr Gene Ther · 2025 · PMID 39225214 · Publisher ↗
Developing delivery vectors capable of transducing genetic material across the lung epithelia and mucus barrier is a major challenge and of great interest to enable gene therapies to treat pulmonary diseases. Recombinant...
Developing delivery vectors capable of transducing genetic material across the lung epithelia and mucus barrier is a major challenge and of great interest to enable gene therapies to treat pulmonary diseases. Recombinant Adeno-associated Viruses (rAAVs) have emerged as attractive candidates among viral and non-viral vectors due to their broad tissue tropism, ability to transduce dividing and quiescent cells, and their safety profile in current human applications. While rAAVs have demonstrated safety in earlier clinical trials for lung disease applications, there are still some limitations regarding rAAV-transgene delivery in pulmonary cells. Thus, further improvements in rAAV engineering are needed to enhance the effectiveness of rAAV-based therapies for lung diseases. Such therapies could benefit patients with chronic lung diseases, such as asthma, chronic obstructive pulmonary disease, pulmonary hypertension, and cystic fibrosis, among others, by regulating hereditary gene mutations or acquired gene deregulations causing these conditions. Alongside therapeutic development, advances in the rAAV production process are essential to meet increasing production demands, while reducing manufacturing costs. This review discusses current challenges and recent advances in the field of rAAV engineering and manufacturing to encourage the clinical development of new pulmonary gene therapy treatments.
Hereditary Patterns and Genetic Associations in Obsessive-Compulsive Disorder (OCD): Neuropsychiatric Insights, Genetic Influences, and Treatment Perspectives.
Dhiman A, Mehan S, Khan Z … +3 more , Tiwari A, Gupta GD, Narula AS
Curr Gene Ther · 2025 · PMID 39219434 · Full text
Obsessive-Compulsive Disorder (OCD), a prevalent neuropsychiatric condition, affects approximately 2%-3% of the global population. This paper provides an extensive overview of OCD, detailing its clinical manifestations,...
Obsessive-Compulsive Disorder (OCD), a prevalent neuropsychiatric condition, affects approximately 2%-3% of the global population. This paper provides an extensive overview of OCD, detailing its clinical manifestations, neurobiological underpinnings, and therapeutic approaches. It examines OCD's classification shift in the DSM-5, the role of the cortico-striatothalamo- cortical pathway in its development, and the various factors contributing to its etiology, such as genes, environmental factors, and genetic predispositions. The challenges in diagnosing OCD and the effectiveness of both psychological and pharmacotherapeutic treatments are discussed. The paper also highlights the significant overlap between OCD and other mental health disorders, emphasizing its impact on global disability. Moreover, the role of genetic factors in OCD, including twin studies and gene association studies, is elaborated, underscoring the complex interplay of hereditary and environmental influences in its manifestation. The review further delves into the polygenic nature of OCD, illustrating how multiple genes contribute to its development, and explores the implications of genetic studies in understanding the disorder's complexity. Additionally, this research study delves into the concept of polygenic inheritance in complex diseases, highlighting the role of multiple genes in increasing OCD risk. A Genome-wide Association Study (GWAS) is employed to assess Single Nucleotide Polymorphisms (SNPs) to unearth genetic associations with OCD. This comprehensive analysis provides valuable insights into OCD's genetic landscape, paving the way for enhanced diagnostic approaches and treatment modalities.
miRNA-Targeted Vaccines: A Promising Approach for Viral Attenuation and Immunogenicity Enhancement.
Debnath A, Mazumder R, Mazumder A … +10 more , Tripathi S, Dua A, Singh RK, Mangal S, Sanchitra J, Pandey P, Pal B, Chaudhary H, Sharma P, Srivastava S
Curr Gene Ther · 2025 · PMID 39092652 · Publisher ↗
MicroRNAs (miRNAs) have emerged as a significant tool in the realm of vaccinology, offering novel approaches to vaccine development. This study investigates the potential of miRNAs in the development of advanced vaccines...
MicroRNAs (miRNAs) have emerged as a significant tool in the realm of vaccinology, offering novel approaches to vaccine development. This study investigates the potential of miRNAs in the development of advanced vaccines, with an emphasis on how they regulate immune response and control viral replication. We go over the molecular features of miRNAs, such as their capacity to direct post-transcriptional regulation toward mRNAs, hence regulating the expression of genes in diverse tissues and cells. This property is harnessed to develop live attenuated vaccines that are tissue-specific, enhancing safety and immunogenicity. The review highlights recent advancements in using miRNA-targeted vaccines against viruses like influenza, poliovirus, and tick-borne encephalitis virus, demonstrating their attenuated replication in specific tissues while retaining immunogenicity. We also explored the function of miRNAs in the biology of cancer, highlighting their potential to develop cancer vaccines through targeting miRNAs that are overexpressed in tumor cells. The difficulties in developing miRNA vaccines are also covered in this work, including delivery, stability, off-target effects, and the requirement for individualized cancer treatment plans. We wrap off by discussing the potential of miRNA vaccines and highlighting how they will influence the development of vaccination techniques for cancer and infectious diseases in the future.
Alternative Splicing of Pre-mRNA Matters in Oral Diseases.
Yue M, Jia R
Curr Gene Ther · 2025 · PMID 39075952 · Publisher ↗
Alternative splicing (AS) of pre-mRNA occurs widely in human genes to produce multiple isoforms with different or even opposite functions. Aberrant AS is often associated with gene mutations and can be corrected by gene...
Alternative splicing (AS) of pre-mRNA occurs widely in human genes to produce multiple isoforms with different or even opposite functions. Aberrant AS is often associated with gene mutations and can be corrected by gene therapy. Oral diseases are important public health problems worldwide. Accumulated pieces of evidence demonstrate that AS of pathogenic genes plays key roles in some oral diseases. However, considering the extensiveness and complexity of AS, it may affect the initiation and development of oral diseases deeply and widely. This review describes the diversity of AS and resulting isoforms in genetic, infectious, and malignant oral diseases and highlights the key roles of AS in determining the function of isoforms and the occurrence and progression of these diseases. The studies of alternative splicing may provide great opportunities for the understanding and treatment of oral diseases.
Effect of Bovine Lactoferrin Treatment on Iron Homeostasis and Gene Expression Changes in Multiple Organ Dysfunctions During Wound Healing Process in Rats.
Bozkurt AS, Yılmaz ŞG
Curr Gene Ther · 2024 · PMID 39005063 · Publisher ↗
BACKGROUND: Injury systemically disrupts the homeostatic balance and can cause organ failure. LF mediates both iron-dependent and iron-independent mechanisms, and the role of LF in regulating iron homeostasis is vital in...
BACKGROUND: Injury systemically disrupts the homeostatic balance and can cause organ failure. LF mediates both iron-dependent and iron-independent mechanisms, and the role of LF in regulating iron homeostasis is vital in terms of metabolism. OBJECTIVES: In this study, we evaluated the organ-level effect and gene expression change of bLf in the cutaneous repair process. MATERIALS AND METHODS: An excisional full-thickness skin defect (FTSD) wound model was created in male Sprague Dawley rats (180-250 g) (n = 48) fed a high-fat diet (HFD) and the and genes and iron metabolism were evaluated. The animals were randomly divided into 6 groups: 1- Control, 2- bLf (200 mg/kg/day, oral), 3- FTSD (12 mm in diameter, dorsal), 4- HFD + bLf, 5- HFD + FTSD, 6- HFD + FTSD + bLf. Histologically, iron accumulation was demonstrated by Prussian blue staining in the liver, kidney, and intestinal tissues. Gene expression analysis was performed with qPCR. RESULTS: Histologically, iron accumulation was demonstrated by Prussian blue staining in the liver, kidney, and intestinal tissues. Prussian blue reactions were detected in the kidney. and genes in kidney and liver tissue were statistically significant (P < 0.05) except for the gene (P > 0.05). Expression changes of the three genes were not statistically significant in analyses of rat intestinal tissue (P = 0.057). CONCLUSION: In the organ-level ferroptotic damage mechanism triggered by wound formation. BLf controls the expression of three genes and manages iron deposition in these three tissues. In addition, it suppressed the increase in iron that would drive the cell to ferroptosis and anemia caused by inflammation, thereby eliminating iron deposition in the tissues.
Biogenesis and Function of circRNAs in Pulmonary Fibrosis.
Zhang S, Hu W, Lv C … +1 more , Song X
Curr Gene Ther · 2024 · PMID 39005062 · Publisher ↗
Pulmonary fibrosis is a class of fibrosing interstitial lung diseases caused by many pathogenic factors inside and outside the lung, with unknown mechanisms and without effective treatment. Therefore, a comprehensive und...
Pulmonary fibrosis is a class of fibrosing interstitial lung diseases caused by many pathogenic factors inside and outside the lung, with unknown mechanisms and without effective treatment. Therefore, a comprehensive understanding of the molecular mechanism implicated in pulmonary fibrosis pathogenesis is urgently needed to develop new and effective measures. Although circRNAs have been widely acknowledged as new contributors to the occurrence and development of diseases, only a small number of circRNAs have been functionally characterized in pulmonary fibrosis. Here, we systematically review the biogenesis and functions of circRNAs and focus on how circRNAs participate in pulmonary fibrogenesis by influencing various cell fates. Meanwhile, we analyze the current exploration of circRNAs as a diagnostic biomarker, vaccine, and therapeutic target in pulmonary fibrosis and objectively discuss the challenges of circRNA- based therapy for pulmonary fibrosis. We hope that the review of the implication of circRNAs will provide new insights into the development circRNA-based approaches to treat pulmonary fibrosis.
The Functions and Application Prospects of Hepatocyte Growth Factor in Reproduction.
Mi X, Chen C, Feng C … +4 more , Qin Y, Chen ZJ, Yang Y, Zhao S
Curr Gene Ther · 2024 · PMID 39005061 · Publisher ↗
Hepatocyte growth factor (HGF) is expressed in multiple systems and mediates a variety of biological activities, such as mitosis, motility, and morphogenesis. A growing number of studies have revealed the expression patt...
Hepatocyte growth factor (HGF) is expressed in multiple systems and mediates a variety of biological activities, such as mitosis, motility, and morphogenesis. A growing number of studies have revealed the expression patterns and functions of HGF in ovarian and testicular physiology from the prenatal to the adult stage. HGF regulates folliculogenesis and steroidogenesis by modulating the functions of theca cells and granulosa cells in the ovary. It also mediates somatic cell proliferation and steroidogenesis, thereby affecting spermatogenesis in males. In addition to its physiological effects on the reproductive system, HGF has shown advantages in preclinical studies over recent years for the treatment of male and female infertility, particularly in women with premature ovarian insufficiency. This review aims to summarize the pleiotropic functions of HGF in the reproductive system and to provide prospects for its clinical application.
Knockdown of hsa_circ_0102231 Impedes the Progression of Liver Cancer through the miR-873-SOX4 Axis.
Qian J, Jiang B, Qin Z … +1 more , Tan Y
Curr Gene Ther · 2025 · PMID 38963113 · Publisher ↗
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity. AIMS: The objective of this study was to investigate the role of circula...
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity. AIMS: The objective of this study was to investigate the role of circular RNA 0102231 (hsa_circ_ 0102231) in the progression of liver cancer. METHODS: In this study, quantitative polymerase chain reaction experiments were performed to quantify the hsa_circ_0102231 level in different liver cancer cell lines. Bioinformatics analysis, as well as a dual-luciferase reporter and RNA pull-down assay, were used to identify putative hsa_circ_ 0102231 downstream targets. Colony formation and CCK8 assays were utilized to examine cell proliferation, whereas Transwell assays were employed to monitor cell migration. Lastly, the role of hsa_circ_0102231 in liver cancer was assessed in a subcutaneous xenograft model. RESULTS: The expression of hsa_circ_0102231 increased significantly in HepG2 and Huh-7 cells compared with controls, and hsa_circ_0102231 knockdown inhibited cell proliferation and migration and . Bioinformatics analysis, as well as a dual-luciferase reporter and RNA pulldown assay, revealed that miR-873 and SOX4 were hsa_circ_0102231 downstream targets. miR-873 inhibition or SOX4 overexpression rescued the proliferation and migration of HepG2 and Huh-7 cells after hsa_circ_0102231 knockdown. Furthermore, SOX4 overexpression reversed the miR-873-induced inhibition of cell migration and proliferation . CONCLUSION: These results show that hsa_circ_0102231 knockdown impedes the progression of liver cancer by regulating the miR-873/SOX4 axis. However, further studies are needed to determine whether hsa_circ_0102231 may be a therapeutic target in liver cancer.
Significance of Ribonucleoside-diphosphate Reductase Subunit M2 in Lung Adenocarcinoma.
Wang XJ, Huo YX, Yang PJ … +2 more , Gao J, Hu WD
Curr Gene Ther · 2025 · PMID 38920074 · Publisher ↗
INTRODUCTION: The Ribonucleoside-diphosphate Reductase subunit M2 (RRM2) is known to be overexpressed in various cancers, though its specific functional implications remain unclear. This aims to elucidate the role of RRM...
INTRODUCTION: The Ribonucleoside-diphosphate Reductase subunit M2 (RRM2) is known to be overexpressed in various cancers, though its specific functional implications remain unclear. This aims to elucidate the role of RRM2 in the progression of Lung Adenocarcinoma (LUAD) by exploring its involvement and potential impact. METHODS: RRM2 data were sourced from multiple databases to assess its diagnostic and prognostic significance in LUAD. We evaluated the association between RRM2 expression and immune cell infiltration, analyzed its function, and explored the effects of modulating RRM2 expression on LUAD cell characteristics through laboratory experiments. RESULTS: RRM2 was significantly upregulated in LUAD tissues and cells compared to normal counterparts (p < 0.05), with rare genetic alterations noted (approximately 2%). This overexpression clearly distinguished LUAD from normal tissue (area under the curve (AUC): 0.963, 95% confidence intervals (CI): 0.946-0.981). Elevated RRM2 expression was significantly associated with adverse clinicopathological characteristics and poor prognosis in LUAD patients. Furthermore, a positive association was observed between RRM2 expression and immune cell infiltration. Pathway analysis revealed a critical connection between RRM2 and the cell cycle signaling pathway within LUAD. Targeting RRM2 inhibition effectively suppressed LUAD cell proliferation, migration, and invasion while promoting apoptosis. This intervention also modified the expression of several crucial proteins, including the downregulation of CDC25A, CDC25C, RAD1, Bcl-2, and PPM1D and the upregulation of TP53 and Bax (p < 0.05). CONCLUSION: Our findings highlight the potential utility of RRM2 expression as a biomarker for diagnosing and predicting prognosis in LUAD, shedding new light on the role of RRM2 in this malignancy.
Acetylresveratrol (AC-Res): An Evolving Frontier in Modulating Gene Expression.
Panigrahy UP, Buchade RS, Subhadra S … +5 more , Narayanan AK, Gunjal SD, Selvakumari E, Pandey NK, Wal A
Curr Gene Ther · 2025 · PMID 38860906 · Publisher ↗
BACKGROUND: Acetylresveratrol (AC-Res), to date, is a powerful stilbene phytoalexin generated organically or as a component of a plant's defensive system, is a significant plant phenolic chemical portion and is investiga...
BACKGROUND: Acetylresveratrol (AC-Res), to date, is a powerful stilbene phytoalexin generated organically or as a component of a plant's defensive system, is a significant plant phenolic chemical portion and is investigated as a therapy option for a number of disorders. Owing to its inadequate stabilisation and considerable conformation rigidity, the utility of AC-Res as a medication is limited. OBJECTIVE: The current review article outlined the structure of AC-Res, their methods of activity, and the latest technological progress in the administration of these molecules. It is conceivable to deduce that AC-Res has a variety of consequences for the cellular functions of infected cells. METHODS: The literature survey for the present article was gathered from the authentic data published by various peer-reviewed publishers employing Google Scholar and PubMedprioritizing Scopus and Web of Science indexed journals as the search platform focusing on AC-Res pharmacological actions, particularly in the English language. RESULTS: Despite its extensive spectrum of biological and therapeutic applications, AC-Res has become a source of increasing concern. Depending on the researchers, AC-Res possesses radioprotective, cardioprotective, neurological, anti-inflammatory, and anti-microbial potential. It also has anti-cancer and antioxidant properties. CONCLUSION: To avoid non-specific cytotoxicity, optimization efforts are presently emphasizing the possible usage of AC-Res based on nanocrystals, nanoparticles and dendrimers, and nanocrystals. Finally, while using AC-Res in biology is still a way off, researchers agree that if they continue to explore it, AC-Res and similar parts will be recognized as actual possibilities for a variety of things in the next years.
The Role and Treatment Strategies of Ammonia-Related Metabolism in Tumor Microenvironment.
Ye Q, Li D, Zou Y … +1 more , Yuan Y
Curr Gene Ther · 2025 · PMID 38860905 · Publisher ↗
Tumor cells achieve their adaptability through various metabolic reprogramming processes. Among them, ammonia, as a traditional metabolic waste, plays an increasingly important role in the tumor microenvironment along wi...
Tumor cells achieve their adaptability through various metabolic reprogramming processes. Among them, ammonia, as a traditional metabolic waste, plays an increasingly important role in the tumor microenvironment along with its associated metabolites. Other cells in the microenvironment can also reshape the immune status of the microenvironment by regulating ammonia- related metabolism, and targeting this metabolic aspect has emerged as a potential strategy for tumor treatment. In this study, we have systematically reviewed the source and destination of ammonia in tumor cells, as well as the links between ammonia and other biological processes. We have also analyzed the ammonia-related metabolic regulation of other cells (including T cells, macrophages, dendritic cells, natural killer cells, myeloid-derived suppressor cells, and stromal cells) in the tumor microenvironment, and summarized the tumor treatment methods that target this metabolism. Through ammonia-related metabolic reprogramming, tumor cells obtain the energy they need for rapid growth and proliferation. Multiple immune cells and stromal cells in the microenvironment also interact with each other through this metabolic regulation, ultimately leading to immune suppression. Despite the heterogeneity of tumors and the complexity of cellular functions, further research into therapeutic interventions targeting ammonia-related metabolism is warranted. This review has focused on the role and regulation of ammonia-related metabolism in tumor cells and other cells in the microenvironment, and highlighted the efficacy and prospects of targeted ammonia- related metabolism therapy.
Single-cell and Bulk Transcriptomic Analyses Reveal a Stemness and Circadian Rhythm Disturbance-related Signature Predicting Clinical Outcome and Immunotherapy Response in Hepatocellular Carcinoma.
Zhu X, Zhang Z, Zhang J … +5 more , Xiao Y, Wang H, Wang M, Jiang M, Xu Y
Curr Gene Ther · 2025 · PMID 38847249 · Publisher ↗
AIMS: Investigating the impact of stemness-related circadian rhythm disruption (SCRD) on hepatocellular carcinoma (HCC) prognosis and its potential as a predictor for immunotherapy response. BACKGROUND: Circadian disrupt...
AIMS: Investigating the impact of stemness-related circadian rhythm disruption (SCRD) on hepatocellular carcinoma (HCC) prognosis and its potential as a predictor for immunotherapy response. BACKGROUND: Circadian disruption has been linked to tumor progression through its effect on the stemness of cancer cells. OBJECTIVE: Develop a novel signature for SCRD to accurately predict clinical outcomes and immune therapy response in patients with HCC. METHODS: The stemness degree of patients with HCC was assessed based on the stemness index (mRNAsi). The co-expression circadian genes significantly correlated with mRNAsi were identified and defined as stemness- and circadian-related genes (SCRGs). The SCRD scores of samples and cells were calculated based on the SCRGs. Differentially expressed genes with a prognostic value between distinct SCRD groups were identified in bulk and single-cell datasets to develop an SCRD signature. RESULTS: A higher SCRD score indicates a worse patient survival rate. Analysis of the tumor microenvironment revealed a significant correlation between SCRD and infiltrating immune cells. Heterogeneous expression patterns, functional states, genomic variants, and cell-cell interactions between two SCRD populations were revealed by transcriptomic, genomic, and interaction analyses. The robust SCRD signature for predicting immunotherapy response and prognosis in patients with HCC was developed and validated in multiple independent cohorts. CONCLUSIONS: In summary, distinct tumor immune microenvironment patterns were confirmed under SCRD in bulk and single-cell transcriptomic, and SCRD signature associated with clinical outcomes and immunotherapy response was developed and validated in HCC.
Theranostic Potential of Bacteriophages against Oral Squamous Cell Carcinoma.
Easwaran M, Madasamy S, Venkidasamy B
Curr Gene Ther · 2025 · PMID 38808710 · Publisher ↗
Oral Squamous Cell Carcinoma (OSCC) is a widespread and challenging disease that accounts for 94% of cancers of the oral cavity worldwide. Bacteriophages (phages) have shown promise as a potential theranostic agent for t...
Oral Squamous Cell Carcinoma (OSCC) is a widespread and challenging disease that accounts for 94% of cancers of the oral cavity worldwide. Bacteriophages (phages) have shown promise as a potential theranostic agent for the treatment of OSCC. It may offer advantages in overcoming the challenges of conventional methods. Modern high-throughput pyrosequencing techniques confirm the presence of specific bacterial strains associated with OSCC. Bio-panning and filamentous phages facilitate visualization of the peptide on surfaces and show high affinity in OSCC cells. The peptide has the potential to bind integrin (αvβ6), aid in diagnosis, and inhibit the proliferation of OSCC cells. Mimotopes of tumor-associated antigens show cytotoxic and immune responses against cancer cells. Biomarker-based approaches such as transferrin enable early OSCC diagnosis. A modified temperate phage introduces CRISPR-Cas3 to target antimicrobial-resistant bacteria associated with OSCC. The research findings highlight the evolving field of phage diagnostics and therapy and represent a new avenue for non-invasive, targeted approaches to the detection and treatment of OSCC. However, extensive clinical research is required to validate the efficacy of phages in innovative cancer theranostic strategies.
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