Human Cell[JOURNAL]
Sun
200 papers
tRNA-derived small RNAs: emerging regulators of ferroptosis in human diseases.
Zhang J, Liu M, Li Z
Hum Cell · 2025 Sep · PMID 40960548 · Publisher ↗
tRNA-derived small RNAs (tsRNAs) are functional non-coding RNAs that play crucial roles in transcriptional, translational, and epigenetic regulation. Ferroptosis is an iron-dependent form of programmed cell death driven...
tRNA-derived small RNAs (tsRNAs) are functional non-coding RNAs that play crucial roles in transcriptional, translational, and epigenetic regulation. Ferroptosis is an iron-dependent form of programmed cell death driven by lipid peroxidation, and its core mechanisms involve dysregulated iron homeostasis, redox imbalance, and lipid peroxidation. Emerging evidence indicates that tsRNAs serve as pivotal regulators of ferroptosis by targeting key components of the ferroptosis pathway. This regulatory interplay critically influences the activation or suppression of ferroptosis in various human diseases, including non-alcoholic steatohepatitis, perioperative neurocognitive disorders, acute kidney injury, non-small cell lung cancer, gastric cancer, diabetic kidney disease, atrial fibrillation, acute pancreatitis, depression, and acute lung injury, thereby affecting disease pathogenesis, progression, and therapeutic responses. This review summarizes the mechanisms underlying the interplay between tsRNAs and ferroptosis in human diseases and highlights the potential of tsRNAs as novel regulators of ferroptosis, providing insights into disease mechanisms.
A stem cell-based toolkit to model Angelman syndrome caused by paternal uniparental disomy of chromosome 15.
Cazaux Mateus F, Camões Dos Santos J, Arez M … +2 more , Bekman EP, da Rocha ST
Hum Cell · 2025 Sep · PMID 40956516 · Full text
Angelman syndrome is a rare neurodevelopmental disorder caused by the loss of function of the maternally inherited UBE3A gene within the chr15q11-q13 region. This gene is subjected to a tissue-specific form of genomic im...
Angelman syndrome is a rare neurodevelopmental disorder caused by the loss of function of the maternally inherited UBE3A gene within the chr15q11-q13 region. This gene is subjected to a tissue-specific form of genomic imprinting leading to the silencing of the paternal allele in neurons. Angelman syndrome can result from various (epi)genetic mechanisms, with paternal uniparental disomy of chromosome 15 (patUPD15) being one of the rarest and least studied due to the absence of suitable models. To address this gap, we generated three independent induced pluripotent stem cell (iPSC) lines from individuals with Angelman syndrome caused by patUPD15, alongside genetically matched unaffected familial controls. Peripheral blood mononuclear cells (PBMCs) were reprogrammed into iPSCs using a non-integrative Sendai virus-based approach expressing the Yamanaka factors. All iPSC lines underwent rigorous quality control, confirming stem cell identity, trilineage differentiation potential, and genetic and epigenetic integrity. This newly established iPSC toolkit provides a powerful platform to investigate the molecular underpinnings of Angelman syndrome caused by patUPD15, paving the way for future translational research and therapeutic development tailored for this understudied form of the disorder.
Melatonin, ROR-α and circadian rhythm in liver.
Srinivasa S, Charmanna SO, Nayak RR … +2 more , Karunakara SH, Santhekadur PK
Hum Cell · 2025 Sep · PMID 40956504 · Publisher ↗
The liver is the largest internal organ. Several critical functions are attributed to the liver which include metabolism, synthesis of serum proteins, excretion, detoxification, and various physiological processes essent...
The liver is the largest internal organ. Several critical functions are attributed to the liver which include metabolism, synthesis of serum proteins, excretion, detoxification, and various physiological processes essential for maintaining body homeostasis. Its unique regenerative capacity helps the liver to restore itself fully after injury. This process involves all hepatocytes with or without the involvement of stem cells. The function of the liver is known to be regulated by circadian rhythm, which includes feeding-fasting cycles and the maintenance of the suprachiasmatic nucleus (SCN) that regulates as a master clock. The normal functioning of the liver is critical to the overall maintenance of homeostasis as it serves as a peripheral clock, suggesting a potential link between the SCN and liver. Aberrations in these circadian rhythms have been linked to various chronic hepatic diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD), which can lead to Hepatocellular carcinoma (HCC). This mini review explores the significance of circadian rhythm in liver function, with a focus on the role of melatonin and nuclear receptors such as Retinoic acid receptor-related orphan receptor-alpha (RORα), which is a known melatonin receptor critical to sustaining these rhythms that can influence biological functions, including immune system functioning, cell growth, and differentiation. Further, RORα is identified as one of the key regulators of inflammation and acts as a potential tumor suppressor, particularly in the context of HCC. This review explores the interplay between RORα, melatonin, and circadian rhythm and discusses the underpinnings that offer insights into the role of circadian rhythm disruption in HCC development and novel therapeutic strategies targeting circadian rhythm modulations to mitigate HCC.
Establishment of KGAS, a cell line derived from gastric-type adenocarcinoma of the uterine cervix.
Yamada H, Yokoi A, Asano-Inami E … +6 more , Kitagawa M, Yoshida K, Suzuki K, Nishio S, Kajiyama H, Tsuda N
Hum Cell · 2025 Sep · PMID 40952575 · Full text
Gastric-type adenocarcinoma (GAS) of the uterine cervix is a rare and aggressive subtype of cervical adenocarcinoma characterized by intrinsic resistance to chemotherapy and poor clinical outcomes due to the lack of effe...
Gastric-type adenocarcinoma (GAS) of the uterine cervix is a rare and aggressive subtype of cervical adenocarcinoma characterized by intrinsic resistance to chemotherapy and poor clinical outcomes due to the lack of effective treatment options. To address this critical unmet need, we established a novel GAS-derived cell line, KGAS, from ascitic fluid collected from a patient with recurrent GAS. Short tandem repeat (STR) analysis confirmed the genetic identity between the primary tumor and the cell line. Upon transplantation into immunocompromised mice, KGAS cells formed tumors that expressed Claudin-18 and MUC6, clinically recognized markers of GAS. Furthermore, KGAS cells exhibited marked resistance to paclitaxel and carboplatin, showing significantly reduced growth inhibition compared to HeLa cells. We also established a paclitaxel- and carboplatin-resistant subline, rKGAS, and performed microRNA (miRNA) sequencing to explore the molecular basis of acquired chemoresistance. Seventeen differentially expressed miRNAs were identified between KGAS and rKGAS cells. Upregulated miRNAs in rKGAS were predicted to target oncogenes such as BCL2, MET, SIRT1, and VEGFA, whereas downregulated miRNAs were associated with tumor suppressor genes, including IGF1R, TNFAIP3, and MTOR. The KGAS and rKGAS cell lines represent valuable preclinical models for elucidating the molecular mechanisms of chemoresistance and malignant progression in cervical GAS, and may contribute to the development of novel therapeutic strategies for this challenging cancer subtype.
The SWI/SNF chromatin remodeling complex subunit BAF53B as an immunohistochemical marker for neuroendocrine neoplasms.
Sakurai K, Ochiai M, Kojima K … +4 more , Kato K, Ando T, Kato T, Ito H
Hum Cell · 2025 Sep · PMID 40946270 · Publisher ↗
The Switch/Sucrose Nonfermentable (SWI/SNF) complexes are chromatin remodeling factors that consist of multiple protein subunits. Each subunit plays a distinct role in gene regulation and is aberrantly expressed in tumor...
The Switch/Sucrose Nonfermentable (SWI/SNF) complexes are chromatin remodeling factors that consist of multiple protein subunits. Each subunit plays a distinct role in gene regulation and is aberrantly expressed in tumors, such as neuroendocrine neoplasms (NENs). BRG1-associated factor 53B (BAF53B), which is also known as ACTL6B, is a neuron-specific subunit that acts as a regulator during neurogenesis. Because the BAF53B expression pattern in tumors is unknown, the present study investigated the expression in cell lines and tissues. Publicly available transcriptome data indicated that BAF53B mRNA was highly expressed in NEN-derived cell lines. We performed immunohistochemical staining on tissue microarrays of different types of NENs with neuroendocrine (NE) marker expression (n = 117) (small cell lung carcinoma (SCLC)lung carcinoid (LC), gastroenteropancreatic-NEN (GEP-NEN), esophageal neuroendocrine carcinoma (ENEC), medullary thyroid carcinoma (MTC), neuroblastoma (NB), and pheochromocytoma (PHEO)) and non-NENs (n = 178). While few positive cells were observed in many cases of non-NENs (e.g., lung adenocarcinoma), positive expression was found in cases of NENs (SCLC (14/19, 73.7%), LC (12/16, 75.0%), GEP-NEN (4/9, 44.4%), ENEC (1/2, 50.0%), MTC (24/27, 88.9%), NB (18/20, 90.0%), and PHEO (16/24, 66.7%)). In NCI-H889 cells, BAF53B knockdown did not affect the cellular viability, and its effect on NE marker expression was only marginal. However, a gene expression microarray analysis suggested that BAF53B-regulated genes were associated with the development and progression of NENs. Our analysis revealed that BAF53B was an immunohistochemical marker for specific NENs, indicating its potentially important role in the pathogenesis.
Apigenin inhibits endothelial-to-mesenchymal transition of coronary artery endothelial cells and myocardial fibrosis by regulating ribosome biogenesis through GTPBP4 modulation.
Hu X, Yang Z, Tang R … +4 more , Lv Z, Zou T, Dou Y, Li H
Hum Cell · 2025 Sep · PMID 40938540 · Publisher ↗
Myocardial fibrosis is a complex pathological process that often leads to myocardial dysfunction, heart failure, and ultimately, death. A critical contributor to the development of cardiac fibrosis is the endothelial-to-...
Myocardial fibrosis is a complex pathological process that often leads to myocardial dysfunction, heart failure, and ultimately, death. A critical contributor to the development of cardiac fibrosis is the endothelial-to-mesenchymal transition (EndMT). Apigenin, a natural compound derived from Matricaria chamomilla, has shown potential anti-fibrotic effects, although its precise mechanism of action is not fully understood. This study investigated the effects of apigenin (API) on EndMT and myocardial fibrosis using an in vitro human coronary artery endothelial cell EndMT model and an in vivo animal model of fibrosis. At appropriate concentrations, apigenin significantly inhibited TGF-β1-induced EndMT and myocardial fibrosis without affecting cell viability. Mechanistically, we found that apigenin suppressed ribosome biogenesis in coronary endothelial cells. Through differential gene screening, GTP-binding protein 4 (GTPBP4) was identified as a key target gene regulating ribosome biogenesis during the progression of myocardial fibrosis. Our results indicate that GTPBP4 plays a pivotal role in the apigenin-mediated inhibition of both ribosome biogenesis and EndMT in these cells. By downregulating GTPBP4 expression, apigenin suppressed EndMT, alleviated myocardial fibrosis, improved cardiac function, and reduced biomarkers of myocardial injury. These findings demonstrate for the first time that apigenin mitigates myocardial fibrosis and EndMT by inhibiting GTPBP4 expression, positioning apigenin as a promising therapeutic candidate for the prevention and treatment of myocardial fibrosis.
Correction: Long non-coding RNA DUXAP10 exerts oncogenic properties in osteosarcoma by recruiting HuR to enhance SOX18 mRNA stability.
Wang G, Zhang Q, Wang Q … +4 more , Wang J, Chen L, Sun Q, Miao D
Hum Cell · 2025 Sep · PMID 40938474 · Full text
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SIRT1 as a potential target for age-related eye diseases: mechanisms and therapeutic strategies.
Liu H, Ouyang Y, Ge H
Hum Cell · 2025 Sep · PMID 40914928 · Publisher ↗
Age-related eye diseases (AREDs) are the leading cause of visual impairment in the elderly, affecting the structure of the anterior and posterior segments of the eye, significantly reducing the quality of life of patient...
Age-related eye diseases (AREDs) are the leading cause of visual impairment in the elderly, affecting the structure of the anterior and posterior segments of the eye, significantly reducing the quality of life of patients, and even leading to irreversible blindness. Typical AREDs include age-related cataract (ARC), dry eye disease (DED), age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), the global prevalence of which continues to rise, becoming a serious public health concern. SIRT1 is an NAD + dependent deacetylase, which plays an important physiological regulatory role in ocular tissues, mainly affecting gene expression and various cellular processes by regulating the acetylation status of substrate proteins. Studies have shown that SIRT1 plays a key role in oxidative stress, inflammation, autophagy, apoptosis and metabolism, and its expression or activity decreases can accelerate cell senescence and promote the occurrence and development of AREDs. In addition, SIRT1 expression levels and changes in its activity have been shown to be strongly associated with AREDs, making it a potential target for disease intervention and therapy. Therefore, this review systematically summarizes the biological role and regulatory mechanism of SIRT1 in AREDs, and explored its potential value as a therapeutic target, providing theoretical basis for future drug development and clinical transformation.
USF1-induced RPS6KB2 activation influences aggressive phenotype in B-cell non-Hodgkin lymphoma.
Liu Z, Song X, Liu Z … +3 more , He X, Gao H, Liu X
Hum Cell · 2025 Aug · PMID 40886264 · Publisher ↗
B-cell non-Hodgkin lymphoma (B-NHL) is a diverse group of aggressive lymphoid malignancies characterized by its molecular complexity. This study investigated the role of the upstream stimulatory factor 1 (USF1)-ribosomal...
B-cell non-Hodgkin lymphoma (B-NHL) is a diverse group of aggressive lymphoid malignancies characterized by its molecular complexity. This study investigated the role of the upstream stimulatory factor 1 (USF1)-ribosomal protein S6 kinase B2 (RPS6KB2) axis in B-NHL progression through the AKT/HDM2 (also known as MDM2)/p53 signaling pathway. Using data from the GEO database, RPS6KB2 was identified to be overexpressed in B-NHL, which was confirmed by RT-qPCR, immunohistochemistry, and western blotting in both B-NHL tissues and cell lines. Functional studies revealed that RPS6KB2 knockdown reduced cell proliferation, migration, and tumor growth, while promoting apoptosis, effects that could be reversed by the AKT activator SC79. Bioinformatics analysis showed that USF1 activated the transcription of RPS6KB2 by directly binding to its promoter region. USF1 downregulation inhibited B-NHL progression, which was rescued by RPS6KB2 overexpression. These findings suggest that the USF1-RPS6KB2 axis contributes to B-NHL progression by activating the AKT/HDM2/p53 pathway.
FTO inhibited miR-487a-3p biosynthesis via N6-methyladenosine-dependent pathway to promote WNT5A-mediated osteogenic differentiation of adipose-derived stem cells.
Li Y, Yue Y, Cen C … +1 more , Liu B
Hum Cell · 2025 Aug · PMID 40864302 · Publisher ↗
miR-487a-3p shows the potential of modulating adipose-derived stem cells (ADSCs) differentiation. This study aimed to investigate the mechanism of miR-487a-3p on the osteogenic differentiation of ADSCs. In this work, ADS...
miR-487a-3p shows the potential of modulating adipose-derived stem cells (ADSCs) differentiation. This study aimed to investigate the mechanism of miR-487a-3p on the osteogenic differentiation of ADSCs. In this work, ADSCs were induced to differentiate into osteoblasts. miR-487a-3p were regulated by miRNA mimics or inhibitors in ADSCs. Wnt family member 5A (WNT5A) siRNA was used to reverse miR-487a-3p inhibitor-induced effects on WNT5A expression in ADSCs. Fat mass and obesity-associated protein (FTO) in ADSCs were altered by shRNAs or overexpression vectors. Calcium nodule, ALP activity, and biomarkers of osteogenic differentiation (OD) were investigated. Rats received ovariectomy (OVX) to construct osteoporosis (OP) model, followed by ADSCs transplantation. Histopathological changes, bone histomorphometry, and detection of OD biomarkers were performed. We found that osteogenesis induced a decrease in miR-487a-3p expression and an increase in FTO expression. miR-487a-3p upregulation inhibited the OD of ADSCs, including decreases in calcium nodule formation, ALP activity, and OD biomarkers. miR-487a-3p downregulation showed the opposite role in OD. miR-487a-3p negatively regulated WNT5A in ADSCs. WNT5A silence reversed the effect of miR-487a-3p downregulation on OD. FTO silence caused the increase in m6A of pri-miR-487a. FTO overexpression inhibited DGCR8 recruitment in pri-miR-487a, and reversed the effect of miR-487a-3p upregulation in OD. ADSCs transplantation improved OP symptom in rats, including improvement of femur tissue, increase in percent bone volume and trabecular number, and upregulation in OD biomarkers. miR-487a-3p downregulation enhanced the therapeutic role of ADSC in rats with OP. Collectively, FTO regulated pri-miR-487a maturation via m6A-dependent pathway, which altered the WNT5A-mediated osteogenesis of ADSCs.
100% Fish oil-based lipid emulsion inhibits hepatic stellate cell activation via suppression of the TGF-β1 autocrine signaling.
Watanabe R, Morii M, Yamagata K … +4 more , Ebihara T, Sasaki T, Mezaki Y, Mizuno M
Hum Cell · 2025 Aug · PMID 40864218 · Publisher ↗
Intestinal failure-associated liver disease (IFALD) is a life-threatening complication of short bowel syndrome (SBS), characterized by cholestasis, hepatic steatosis, and hepatic fibrosis. Fish oil-based lipid emulsion (...
Intestinal failure-associated liver disease (IFALD) is a life-threatening complication of short bowel syndrome (SBS), characterized by cholestasis, hepatic steatosis, and hepatic fibrosis. Fish oil-based lipid emulsion (FO) has been demonstrated to ameliorate IFALD compared to soybean oil lipid emulsion (SO). However, the mechanisms underlying the beneficial effects of FO remain elusive. This study investigated the effects of FO on the activation of hepatic stellate cells (HSCs) that are primarily responsible for liver fibrosis by differentiating into fibroblasts in a transforming growth factor-β1 (TGF-β1) dependent manner. The human HSCs line LX-2 cells were stimulated with TGF-β1 in the presence of FO and SO. FO, but not SO, inhibited the degradation of lipid droplets induced by TGF-β1, suggesting that FO maintains HSCs in a quiescent state. Furthermore, FO suppressed LX-2 cell proliferation and partially abolished the autocrine regulation of TGF-β1 and subsequent activation of HSCs, as evidenced by the reduced expression of alpha-1 type I collagen (Col1a1) mRNA. These effects were specific to LX-2 and were not observed in the human hepatocellular carcinoma cell line HuH-7. The unique fatty acid composition of FO, characterized by high levels of long-chain polyunsaturated fatty acids with carbon chains of 20 or more, may contribute to its antifibrotic properties. These findings suggest that FO suppresses excessive HSCs activation while maintaining physiological functions, providing novel insights into the antifibrotic mechanisms of FO.
Nicotinamide N-methyltransferase enhances paclitaxel resistance in ovarian clear cell carcinoma.
Kikuchi-Koike R, Sakamoto M, Sasajima Y … +12 more , Miyagawa Y, Uozaki H, Umayahara K, Hashimoto K, Takahashi Y, Takasaki K, Kihira C, Nishida H, Ichinose T, Hirano M, Hiraike H, Nagasaka K
Hum Cell · 2025 Aug · PMID 40853419 · Full text
Nicotinamide N-methyltransferase (NNMT) is an S-adenosyl-l-methionine (SAM)-dependent cytosolic enzyme, and a growing body of evidence suggest that it plays an essential role in cancer progression. Recently, NNMT has a r...
Nicotinamide N-methyltransferase (NNMT) is an S-adenosyl-l-methionine (SAM)-dependent cytosolic enzyme, and a growing body of evidence suggest that it plays an essential role in cancer progression. Recently, NNMT has a role in methylation metabolism and tumorigenesis and was associated with a poor prognosis against numerous cancers. In addition, it has been reported that NNMT has been overexpressed in the stroma of advanced high-grade serous carcinoma and may contribute to decreased survival. This study aimed to identify novel biomarkers to predict resistance and investigate their clinicopathologic significance in paclitaxel-resistant advanced or recurrent ovarian clear cell carcinoma (OCCC). Fluorescence-labeled two-dimensional differential gel electrophoresis (2D-DIGE), immunohistochemical, and MASCOT analyses allowed us to identify the cytoplasmic metabolic enzyme NNMT. In cultured cell studies, NNMT protein expression was higher in paclitaxel-resistant OVMANA and OVTOKO cells than in paclitaxel-sensitive KK and ES-2 cells. Furthermore, although analysis of clinical tissue samples showed no association with poor prognosis in 7 individuals with low NNMT expression in the cytoplasm of OCCC cells, high expression of NNMT in the cytoplasm of OCCC cells may be associated with low sensitivity to paclitaxel in OCCC and may have prognostic implications. Therefore, targeting therapy to reduce cytoplasmic NNMT expression levels may increase the sensitivity of OCCC to paclitaxel.
Regulatory T cells in cancer anti-PD-(L)1 therapy.
Mortezaee K
Hum Cell · 2025 Aug · PMID 40853522 · Publisher ↗
Regulatory T cell (Treg) immunome profile and targets in antiprogrammed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) is a subject of extensive research, but there are still complexities in the area due to t...
Regulatory T cell (Treg) immunome profile and targets in antiprogrammed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) is a subject of extensive research, but there are still complexities in the area due to the nature of tumor microenvironment (TME). TME of solid tumors contains factors exerting a range of effects on Tregs including development, recruitment, expansion, stability and their immunosuppressive activity. Anti-PD-1 secondarily causes replenishment of intratumoral Tregs, which further intensify tumor immunosuppression. Besides, Treg depletion may also compromise immune checkpoint inhibitor (ICI) efficacy in addition to its other adversarial effects. Thus, a desired ICI booster is to use agents preferentially acting on intratumoral Tregs. Modulation of hypoxia, and regulation of Treg-related cytokines, chemokines, receptors and chromatin modifying factors in tumor TME provide supplementary approaches to anti-PD-(L)1. Factors acting on Tregs have diverse or even dual functions in TME. Treg expansion inhibitory and immunosuppressive tumor-associated macrophage (TAM) recruitment stimulatory effects of stimulator of interferon genes (STING), effector suppressor Treg activating and tumor-specific CD8 T cell stimulatory effects of interleukin type 2 receptor alpha (IL-2Rα, also called CD25), cell type-dependent dual activities of CXCR3 and inducible T cell costimulatory (ICOS), exposure time-dependent dual effects of glucocorticoid-induced TNFR-related protein (GITR) and CD70 on Tregs and T cells, and exposure level-dependent dual activities of IFN-γ on Tregs are examples require consideration in designing Treg-based strategies. The main direction of this review is to provide updated information about targeting modulators of intratumoral Tregs with agents/compounds aiming to expand anti-PD-(L)1 efficacy and durability in solid tumors.
Simulating tumor complexity: 3D pancreatic tumor spheroid model for improved drug screening.
Subia B, Patel A, Nathwani S … +3 more , Ghoshdastidar K, Jain M, Viswanathan K
Hum Cell · 2025 Aug · PMID 40848084 · Publisher ↗
Most drug discovery studies use 2D cell cultures and animal models for screening new chemical entities (NCEs), which often leads to suboptimal results due to genetic variations, species differences, or lack of most physi...
Most drug discovery studies use 2D cell cultures and animal models for screening new chemical entities (NCEs), which often leads to suboptimal results due to genetic variations, species differences, or lack of most physiological preclinical models. This is one of the most important reasons behind high rate of failure of drug candidate in the clinic, especially in oncology drug development projects. To address this issue, we developed a 3D pancreatic tumor spheroid model that better mimics the parental tumor architecture. We observed similar drug effects on cellular viability in both 2D cultures and 3D spheroids. However, cellular viability alone is insufficient to predict the translation of efficacy into clinical studies. A 3D multicellular tumor model is essential to comprehensively evaluate drug effects on the tumor microenvironment (TME), angiogenesis, and tumor biomarkers. Our model includes 3D monocellular and multicellular spheroids, which demonstrated a more relevant platform for potency evaluation. We used pancreatic ductal adenocarcinoma cells PANC-1 and PANC04.03 to conduct a comprehensive drug screening and assessed spheroid shrinkage and pre-vascularization. We also evaluated RT-qPCR analysis for gene expression of CSC markers (CD44, SOX2, KRT18), EMT markers (αSMA, vimentin) and the apoptotic marker (Annexin A1) under various conditions. Our findings highlighted the significant differences between 2D and 3D cultures, underscoring the importance of 3D multicellular models for predicting therapeutic markers and enabling comprehensive drug evaluation. In this study, MRTX1133 (a Phase I candidate of KRAS-G12D inhibitor) was used for testing our hypothesis. Treating the spheroids with MRTX1133 revealed enhanced drug response profiles compared to 2D cultures. This study underscores the critical importance of 3D multicellular model in preclinical drug screening and their potential to bridge the gap between in vitro studies and clinical outcomes.
Collagen alpha-5(IV) chain activation by nuclear factor 1/C promotes nasopharyngeal carcinoma progression.
Cao Y, Wang P, Li P … +5 more , Wei K, Kang X, Han X, Huai D, Fei B
Hum Cell · 2025 Aug · PMID 40833521 · Publisher ↗
The expression of collagen receptors by cancer cells serves a vital function in the regulation of cell behavior. These receptors are capable of sensing the signals generated by alterations in the collagen state, thereby...
The expression of collagen receptors by cancer cells serves a vital function in the regulation of cell behavior. These receptors are capable of sensing the signals generated by alterations in the collagen state, thereby contributing to the maintenance of cellular homeostasis. The discoidin domain receptor (DDR)1 functions as a critical sensor of collagen fiber state and composition, regulating tumor cell growth, response to therapy, and patient survival. We evaluated the role of collagen alpha-5(IV) chain (COL4A5) in nasopharyngeal carcinoma (NPC) and the detailed mechanism. GSE118719 and GSE68799 datasets were included to identify COL4A5 as a hub gene in NPC. Transcriptional activation of COL4A5 by nuclear factor 1/C (NFIC) mediated DDR1/Akt signaling activation, promoted NPC cell proliferation, migration, invasion, and curbed apoptosis in vitro, and exacerbated malignant progression of subcutaneous tumors in nude mice. NFIC and COL4A5 were significantly overexpressed in the tumors of NPC patients, and their expressions were significantly positively correlated. The overexpression of NFIC and COL4A5 was closely related to the tumor, node, metastases stage of NPC patients. Collectively, our results suggest that NFIC transcriptionally activates COL4A5 and upregulates its expression, which mediates DDR1/Akt signaling and promotes the malignant behavior of NPC cells, leading to NPC progression.
The cell-surface serine protease prostasin is lost during cervical squamous cell carcinogenesis.
Lundgren JG, Flynn MG, List K
Hum Cell · 2025 Aug · PMID 40828246 · Full text
The glycosylphosphatidylinositol (GPI)-anchored serine protease prostasin has been reported to have increased expression with tumor-promoting properties in some cancer types, while expression is lost and prostasin displa...
The glycosylphosphatidylinositol (GPI)-anchored serine protease prostasin has been reported to have increased expression with tumor-promoting properties in some cancer types, while expression is lost and prostasin displays tumor-suppressing properties in other cancer types. Due to these context-dependent and opposing expression patterns and functions of prostasin, characterization of each cancer type is important. In the present study, we aimed to determine the expression of prostasin in the normal cervix and in cervical squamous cell carcinoma (CSCC), the most common type of cervical cancer. We found that prostasin protein is expressed in both murine and human cervix and is consistently localized on the cell surface in suprabasal layers of squamous cells in healthy cervical epithelia. To assess whether prostasin protein is differentially expressed during cervical carcinogenesis, we performed a comprehensive immunohistochemical analysis of prostasin protein expression levels and localization in tissue arrays of paraffin-embedded human cervical carcinomas compared to the corresponding normal tissue. Prostasin protein is expressed in the well-differentiated cellular strata with expression patterns similar to pan-keratin and E-cadherin, and is lost during the dedifferentiation of epithelial cells, a hallmark of high-grade CSCC. The prostasin expression profile, with differential expression in cancer, provide valuable information that may give clues to the function(s) of this protease in normal epithelial biology and carcinogenesis.
The expression of PD-1 ligands in the immune microenvironment was altered in TTF-1-negative lung adenocarcinoma.
Yamada H, Yano H, Matsubara E … +9 more , Zhao S, Shinchi Y, Pan C, Koga T, Fujino K, Fujiwara Y, Ikeda K, Komohara Y, Suzuki M
Hum Cell · 2025 Aug · PMID 40824335 · Full text
Thyroid transcription factor-1 (TTF-1) is a lineage-specific marker for lung adenocarcinoma (LUAD), whereas the relatively minor subset of TTF-1-negative LUADs shows a poor prognosis and a limited response to therapy. Ho...
Thyroid transcription factor-1 (TTF-1) is a lineage-specific marker for lung adenocarcinoma (LUAD), whereas the relatively minor subset of TTF-1-negative LUADs shows a poor prognosis and a limited response to therapy. However, its relationship with the tumor immune microenvironment remains poorly defined. How TTF-1 expression affects the immune context in LUAD was investigated, focusing on tumor-associated macrophages (TAMs) and T-cell infiltration. Immunohistochemical (IHC) analysis of 226 LUAD specimens showed that TTF-1-negative tumors were associated with epidermal growth factor receptor wild-type status, advanced stage, and worse progression-free and cancer-specific survivals. Notably, PD-L1 (programmed death-ligand 1) and PD-L2 expression in TAMs, but not in cancer cells, was significantly reduced in TTF-1-negative tumors. Public single-cell RNA sequencing data confirmed downregulation of CD274 (PD-L1) in TAMs from tumors with low expression of TTF-1-related genes. In contrast, PDCD1LG2 (PD-L2) expression showed less consistent patterns. On IHC analysis, infiltration of CD8 and CD4 T cells was modestly lower in TTF-1-negative tumors, accompanied by decreased HLA class I and II expressions. Transcriptomic analysis of The Cancer Genome Atlas LUAD cohort further showed lower interferon gamma (IFN-γ) signaling and decreased T cell-inflamed gene signatures in the low TTF-1-negative tumors. These findings suggest that TTF-1-negative LUAD exhibits more immune-suppressive features, with a relatively reduced antitumor immune response characterized by decreased T-cell infiltration and INF-γ signaling, which are related to PD-L1 and PD-L2 expressions in TAMs.
Exosomal FGD5-AS1 promotes proliferation of lung cancer cells under hypoxia by inhibiting miR-1179 and activating P-cadherin.
Yang B, Tian Z, Luo Z … +3 more , Yuan Y, Wen Q, Liu Z
Hum Cell · 2025 Aug · PMID 40820190 · Publisher ↗
Lung adenocarcinoma (LUAD) continues to be a major contributor to cancer-related deaths due to its aggressive nature and resistance to current therapies, highlighting the need for novel molecular insights and therapeutic...
Lung adenocarcinoma (LUAD) continues to be a major contributor to cancer-related deaths due to its aggressive nature and resistance to current therapies, highlighting the need for novel molecular insights and therapeutic targets. This study investigated the function of exosomal lncRNA FGD5-AS1 in lung adenocarcinoma (LUAD) and its interaction with miR-1179 and CDH3. We discovered that FGD5-AS1 was substantially overexpressed in LUAD cells and exosomes under hypoxic conditions, while miR-1179, a tumor suppressor, directly targeted and downregulated CDH3. By sponging miR-1179, FGD5-AS1 serves as a competing endogenous RNA (ceRNA) to prevent the suppression of CDH3, thereby promoting LUAD cell growth, movement, and infiltration. It was demonstrated that knockdown of FGD5-AS1 or overexpression of miR-1179 significantly reduced tumor growth in vivo. These results demonstrate a novel exosome-mediated regulatory axis, suggesting that targeting the FGD5-AS1/miR-1179/CDH3 pathway could offer new therapeutic strategies for LUAD.
Establishment and characterization of a new Chinese extrahepatic cholangiocarcinoma cell line, EBC-X1.
Su Y, Tang H, Miao X … +14 more , Yu C, Chai C, Huang W, Li L, Zheng J, Xu T, Jin F, Ye Z, Hu Z, Chen L, Li N, Wu K, Xu H, Zhou W
Hum Cell · 2025 Aug · PMID 40819321 · Publisher ↗
Cholangiocarcinoma (CCA) is a highly heterogeneous primary malignant tumor of the biliary tract. Intrahepatic and extrahepatic cholangiocytes originate from different sources, resulting in significant clinical, epidemiol...
Cholangiocarcinoma (CCA) is a highly heterogeneous primary malignant tumor of the biliary tract. Intrahepatic and extrahepatic cholangiocytes originate from different sources, resulting in significant clinical, epidemiological, molecular, and genetic heterogeneity. Globally, the incidence and mortality rates of CCA are generally increasing, highlighting the need for more foundational research to support advances in clinical diagnosis and treatment. Tumor cell lines remain a crucial tool for unraveling the molecular mechanisms underlying tumor development and for the development of novel therapeutic strategies. The existing CCA cell lines are insufficient to meet research demands, underscoring the urgent need to establish new CCA cell lines. In this study, we successfully established a novel human CCA cell line, designated EBC-X1, derived from a Chinese patient. It exhibits robust proliferative capacity and was successfully passaged for more than 40 generations. STR analysis confirmed that EBC-X1 is a distinct human-derived CCA cell line. The population doubling time was 64.5 h. Karyotypic analysis revealed that EBC-X1 cells exhibit complex karyotypes, with 91% being sub-diploid and 9% being sub-triploid. The representative karyotype is 35, X, der(4), del(5)(q35), der(8), inv(9), der(11), rob(13;15). Upon inoculation into NXG mice, subcutaneous transplant tumors were efficiently formed. EBC-X1 is resistant to paclitaxel, fluorouracil, and oxaliplatin but sensitive to gemcitabine. This model holds significant potential for advancing our understanding of the biological characteristics and molecular mechanisms of distal CCA, as well as for facilitating drug development efforts.
Unveiling the vital role of OGG1 in inflammation, vascular endothelial damage, and cell death in obstetric and gynecological diseases.
Li Y, Zhang W, Wang B … +1 more , Wu F
Hum Cell · 2025 Aug · PMID 40813502 · Full text
The DNA repair enzyme 8-oxoguanine DNA glycosylase-1 (OGG1) plays a crucial role in the initiation of DNA base excision repair pathway by recognizing and excising the oxidative base lesions including 7,8-dihydro-8-oxogua...
The DNA repair enzyme 8-oxoguanine DNA glycosylase-1 (OGG1) plays a crucial role in the initiation of DNA base excision repair pathway by recognizing and excising the oxidative base lesions including 7,8-dihydro-8-oxoguanine (8-oxoG). Beyond its canonical function in DNA repair, OGG1 has been implicated in regulating inflammation-related genes, growth factor expression, and various cell death pathways, including apoptosis, parthanatos, and autophagy. These mechanisms are often involved in obstetric and gynecological disorders, which are frequently characterized by inflammation, endothelial dysfunction, and dysregulated cell death. As such, OGG1 emerges as a potential therapeutic target for these conditions. However, comprehensive reviews detailing OGG1's mechanistic roles in reproductive diseases remain scarce. This review aims to synthesize current knowledge primarily on non-canonical functions of OGG1, with a focus on its potential involvement in disorders such as endometriosis, polycystic ovary syndrome, uterine fibroids, and malignancies, and to highlight its promise as a therapeutic target.
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