Yang X, Wang X, Xiao Q
… +19 more, Ge X, Yu N, Li J, Feng G, Zheng Z, Jiang Y, Lu L, Xia X, Deng L, Zhang T, Wang W, Liu W, Wang J, Xiao Z, Zhou Z, Bi N, Wang H, Chen C, Wang X
Cancer Biol Ther
· 2025 Dec · PMID 40367097
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Trial no. NCT04821778 registered in ClinicalTrials.gov.Trial no. NCT04821778 registered in ClinicalTrials.gov.
Cancer Biol Ther
· 2025 Dec · PMID 40366858
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OBJECTIVE: This study aims to explore the effects of silencing Zic family member 5 (ZIC5) on glucose metabolism and disulfidptosis in lung adenocarcinoma (LUAD) cells. METHODS: Data from The Cancer Genome Atlas (TCGA) wa...OBJECTIVE: This study aims to explore the effects of silencing Zic family member 5 (ZIC5) on glucose metabolism and disulfidptosis in lung adenocarcinoma (LUAD) cells. METHODS: Data from The Cancer Genome Atlas (TCGA) was used to analyze ZIC5 expression in LUAD and its association with patient outcomes. ZIC5 was silenced in A549 and H1299 cells using siRNA. The expression of ZIC5 mRNA and protein was assessed by qRT-PCR and Western blot. Cell proliferation was evaluated through CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays, while glucose uptake, lactate production, and ATP levels were measured to assess energy metabolism. Seahorse XF analysis was used to evaluate extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Disulfidptosis was assessed through NADP/NADPH ratio, glutathione (GSH) content, GSSG/GSH ratio, and immunofluorescence staining. RESULTS: ZIC5 is highly expressed in LUAD and is associated with poor patient prognosis. Silencing ZIC5 significantly reduced its mRNA and protein levels in A549 and H1299 cells, markedly inhibited cell proliferation, and led to significant decreases in glucose uptake, lactate production, ATP levels, ECAR, and OCR. Additionally, silencing ZIC5 resulted in an increased NADP/NADPH ratio, decreased GSH levels, and a reduced GSSG/GSH ratio, alongside classic disulfidptosis features. CONCLUSION: ZIC5 plays a crucial role in promoting LUAD cell proliferation and energy metabolism while inhibiting disulfidptosis. Silencing ZIC5 markedly suppresses these processes, indicating its potential as a therapeutic target in LUAD.
Mallya S, Gangadhar V, Aldrin SE
… +4 more, Acharya M, Kabekkodu SP, Kolathur KK, Chakrabarty S
Cancer Biol Ther
· 2025 Dec · PMID 40353441
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The epidemic of obesity is a growing concern and is one of the major risk factors for several chronic diseases, including several types of cancers. The correlation of breast cancer with obesity has been extensively studi...The epidemic of obesity is a growing concern and is one of the major risk factors for several chronic diseases, including several types of cancers. The correlation of breast cancer with obesity has been extensively studied and involves an interplay of hormonal, metabolic, and genetic factors explored in this review. Inflammation and hormone dysregulation play an important role in promoting a protumorigenic environment through adipose tissue, which is involved in energy storage and functions as an endocrine organ. As a result, various cytokines, primarily proinflammatory in nature, are released, resulting in low-grade inflammation promoting tumor growth. Additionally, obese conditions also induce imbalances in hormones, particularly estrogen and insulin, both of which drive carcinogenesis. Genetic components such as single nucleotide polymorphisms also play critical roles in modulating the correlation between obesity and breast cancer. This review provides a comprehensive overview of various mechanisms underlying obesity and breast cancer incidence and progression.
Currie C, Bjerknes C, Nicol M
… +2 more, Kumar S, Framroze B
Cancer Biol Ther
· 2025 Dec · PMID 40340699
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Increased levels of intratumoral free iron drive more aggressive behavior with the development of treatment resistance and spread in a range of cancers including prostate cancer (PCa). This phenotype is associated with a...Increased levels of intratumoral free iron drive more aggressive behavior with the development of treatment resistance and spread in a range of cancers including prostate cancer (PCa). This phenotype is associated with an increase in TFRC expression and a decrease in FTH1, a profile supporting increased iron acquisition. In this study we investigated the anti-oncogenic effects of two small peptides (FT-002 and FT-005) that upregulate FTH1 expression and downregulate TFRC expression when combined with standard androgen receptor pathway inhibitors (ARPIs) in xenograft models of PCa in male athymic nude mice. The PC3 cell line was used to establish xenografts representing highly aggressive, androgen-resistant PCa and the LNCaP cell line as a model of androgen-sensitive PCa. Both peptides enhanced the anti-tumor efficacy of ARPI therapy. Efficacy was more marked with the combination of the second-generation APRI enzalutamide than the first-generation agent bicalutamide, a result consistent with known resistance mechanisms to different ARPI therapy. Further, the FT-peptide/enzalutamide combination drove tumor regression whereas enzalutamide monotherapy only slowed growth, even in the hormone-sensitive xenograft. The FT-002a-enzalutamide combination was more effective than FT-005 in reducing tumor mass and volume and modulating FTH1 and TFRC expression. The reversal by the peptides of this oncogenic expression pattern points to a reduction in the tumor free iron via increased iron storage in ferritin and a reduction in iron influx via the transferrin receptor. Peptide-mediated modulation of tumor iron metabolism may therefore offer a novel means to enhance ARPI efficacy and delay resistance in advanced prostate cancer.
Lv Y, Li Y, Zhou J
… +7 more, Liu X, Wang D, Wang D, Tong D, Wang S, An H, Kang X
Cancer Biol Ther
· 2025 Dec · PMID 40320567
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Tumor metastasis is a major obstacle for the effective treatment of breast cancer. Some studies showed that exosomes could promote tumor distant metastasis by establishing pre-metastasis niches (PMN). MicroRNAs (miRNAs)...Tumor metastasis is a major obstacle for the effective treatment of breast cancer. Some studies showed that exosomes could promote tumor distant metastasis by establishing pre-metastasis niches (PMN). MicroRNAs (miRNAs) in exosomes play a critical role in tumor development and invasion. We aimed to investigate the effects of exosomal miRNAs derived from breast cancer cells on metastasis. MiRNA sequencing and RT-PCR approach were used to screen potential exosomal miRNAs. We compared the levels of serum exosomal miRNAs from breast cancer patients and those from MCF10A/MCF7/MDA-MB-231 cells. We found that differential exosomal miRNAs screened from patients with metastasis have higher expression levels in exosomes secreted by MDA-MB-231 cells. Using miRNA mimics or inhibitors, exosomal miR-122-5p was found to enhance the secretion levels of chemokine MCP-1 and SDF-1 from WI-38 lung fibroblast cells. In vitro luciferase assay and western blot confirmed the targeting of 3'-untranslated region of MKP-2 and suppression of MKP-2 expression by miR-122-5p in WI-38 cells. Treatment of xenograft mice with exosomal miR-122-5p increased the levels of MCP-1 and SDF-1 in serum, and promoted lung metastasis of breast cancer. In conclusion, we identified exosomal miR-122-5p from breast cancer cells that could promote the chemokine secretion of lung fibroblasts, which might facilitate the chemotaxis and colonization of breast cancer cells in lung tissue.
Cancer Biol Ther
· 2025 Dec · PMID 40269355
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Cisplatin (DDP) resistance is a key factor hindering esophageal cancer (ESCA) treatment. Exosomes have been reported to confer resistance to DDP in various tumor cells. However, the effects of ESCA cell-derived exosomes...Cisplatin (DDP) resistance is a key factor hindering esophageal cancer (ESCA) treatment. Exosomes have been reported to confer resistance to DDP in various tumor cells. However, the effects of ESCA cell-derived exosomes and exosomal human antigen R (HuR) on DDP resistance in cancer cells have not been elucidated. In this study, isolated exosomes were identified by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. CCK-8 and flow cytometry were employed to assess the functional role of exosomes in ESCA DDP-resistant cells and their parental cells. Bioinformatics analysis was performed to identify molecules that were positively associated with HuR and validated using dual-luciferase reporter analysis and RNA immunoprecipitation assays. We found that exosomes from ESCA cells enhance the resistance of drug-resistant cells to DDP. Importantly, HuR protein, but not mRNA, was directly transferred into DDP-resistant cells via exosomes, thereby increasing the level of HuR protein. Mechanistically, HuR positively correlated with Lamin B2 (LMNB2) in ESCA cells, and ESCA DDP-resistant cells transfected with siRNA targeting LMNB2 exhibited reduced cell viability and elevated apoptosis rates. Moreover, the role of ESCA cell-derived exosomes in the transmission of DDP resistance was validated using a nude mouse model. Collectively, our results revealed that exosomes exposed to ESCA cells induced greater drug resistance in DDP-resistant ESCA cells via HuR delivery. Targeting HuR or its positively related target LMNB2 may present new therapeutic opportunities for treating patients with DDP-resistant ESCA.
Rastogi I, Mannone JA, Gibadullin R
… +5 more, Moseman JE, Sidney J, Sette A, McNeel DG, Gellman SH
Cancer Biol Ther
· 2025 Dec · PMID 40200635
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BACKGROUND: Peptide vaccines offer a direct way to initiate an immunogenic response to a defined antigen epitope. However, peptide vaccines are unstable , subject to rapid enzymatic proteolysis. Replacement of an α-amino...BACKGROUND: Peptide vaccines offer a direct way to initiate an immunogenic response to a defined antigen epitope. However, peptide vaccines are unstable , subject to rapid enzymatic proteolysis. Replacement of an α-amino acid residue with a homologous β-amino acid residue (native side chain, but backbone extended by a single CH unit) impairs proteolysis at nearby amide bonds. Therefore, antigen analogues containing α-to-β replacements have been examined for functional mimicry of native all-α antigens. Another group previously took this approach in the ovalbumin (OVA) antigen model by evaluating single α-to-β analogues of the murine major histocompatibility complex (MHC) I-restricted peptide SIINFEKL. METHODS: We re-examined this set of α/β SIINFEKL antigens. We tested the susceptibility to proteolysis in mouse serum and their ability to activate OVA-antigen-specific CD8 T cells . Additionally, we tested the α/β antigens for their ability to induce an antigen-specific immunogenic response in naïve mice and in OVA-expressing tumor-bearing mice. RESULTS: The α/β antigens were comparable to the native antigen in their susceptibility to proteolysis in serum. Each α/β antigen was capable of activating antigen-specific CD8 T cells . However, antigen-specific CD8 T cells induced against α/β antigens were not cross-reactive to the native antigen. Moreover, immunization with α/β analogues did not elicit anti-tumor effects in tumor-bearing mice. CONCLUSIONS: We conclude that even though α/β analogues of the SIINFEKL antigen can elicit a T cell-based response, this class of backbone-modified peptides is not promising from the perspective of antitumor vaccine development.
Liu H, Wang H, Gao W
… +5 more, Yuan Y, Tang T, Sang M, Liu F, Geng C
Cancer Biol Ther
· 2025 Dec · PMID 40176374
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Triple-negative breast cancer (TNBC) is a common malignant disease among females and severely threatens the health of women worldwide. Nowadays, circular RNAs (circRNAs) aroused our interest for their functions in human...Triple-negative breast cancer (TNBC) is a common malignant disease among females and severely threatens the health of women worldwide. Nowadays, circular RNAs (circRNAs) aroused our interest for their functions in human cancers, including TNBC. However, the mechanism of most circRNAs in the progression of TNBC remains unclear. We found a novel circRNA named circATP5C1, whose function in TNBC remains uncovered. Tissue microarray was used to analyze the association between the expression of circATP5C1 and the prognoses of TNBC patients. Gain-and loss-of-function experiments were performed to validate the biological functions of circATP5C1 in different TNBC cell lines. RNA-seq analyses were conducted to find out the target genes regulated by circATP5C1. RNA pull-down assay and mass spectrometry were used to select the proteins associated with circATP5C1. RNA FISH-immunofluorescence and RNA immunoprecipitation (RIP) were complemented to validate the interaction between circATP5C1 and its binding protein. CircATP5C1 was identified to have predictive function in prognosis of TNBC patients. CircATP5C1 advanced the progression of TNBC cells. Mechanistically, Colony stimulating factor 1 (CSF-1) is a vital downstream gene regulated by circATP5C1. The alteration of CSF-1 expression level was validated due to the interaction between circATP5C1 and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2). Rescue experiments demonstrated that circATP5C1 accelerates the progression of TNBC partly via binding with IGF2BP2 to increase the secretion of CSF-1. This study uncovers a novel mechanism of circATP5C1/IGF2BP2/CSF-1 pathway in regulating progression of TNBC.
Xu W, Li W, Kuai D
… +4 more, Li Y, Sun W, Liu X, Xu B
Cancer Biol Ther
· 2025 Dec · PMID 40169935
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Endoplasmic reticulum stress (ERS) has been implicated in the pathogenesis of various cancers, including colon cancer, by regulating tumor cell survival, growth, and immune response. However, the specific genes involved...Endoplasmic reticulum stress (ERS) has been implicated in the pathogenesis of various cancers, including colon cancer, by regulating tumor cell survival, growth, and immune response. However, the specific genes involved in ERS that could serve as prognostic markers in colon cancer remain underexplored. This study aims to identify and validate endoplasmic reticulum stress related genes (ERSRGs) in colon cancer that correlate with patient prognosis, thereby enhancing the understanding of ERS in oncological outcomes and potential therapeutic targeting. We utilized bioinformatics analyses to identify ERSRGs from publicly available colon cancer datasets. Differential expression analysis and survival analysis were performed to assess the prognostic significance of these genes. Validation was conducted through quantitative real-time PCR (RT-qPCR) on selected colon cancer cell lines. Our study identified nine ERS related genes (ASNS, ATF4, ATF6B, BOK, CLU, DDIT3, MANF, SLC39A14, TRAF2) involved in critical pathways including IL-12, PI3K-AKT, IL-7, and IL-23 signaling, and linked to 1-, 3-, and 5-year survival of patients with colon cancer. A multivariate Cox model based on these ERS related genes demonstrated significant prognostic power. Further, TRAF2 strong correlated with immune cells infiltration, suggesting its potential roles in modulating immune responses in the tumor microenvironment. The RT-qPCR validation confirmed the differential expression of these genes in human colon cancer cell lines versus human normal colonic epithelial cell line. The identified ERSRGs could serve as valuable prognostic markers and may offer new insights into the therapeutic targeting of ERS in colon cancer.
Zhu M, Xiang W, Zhu Z
… +4 more, Nie B, Zhen X, Chen C, Wang T
Cancer Biol Ther
· 2025 Dec · PMID 40146196
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Osteosarcoma is the most common primary bone tumor in children and adolescents. Its pathogenesis is complex and poses difficulties in treatment. Autophagy is a cell biological process that plays a crucial role in the mec...Osteosarcoma is the most common primary bone tumor in children and adolescents. Its pathogenesis is complex and poses difficulties in treatment. Autophagy is a cell biological process that plays a crucial role in the mechanistic study and treatment of osteosarcoma. The objective of this study is to evaluate the past research progress from 2007 to 2023 and visualize the key research directions through bibliometric methods. Relevant publications published from the start of 2007 to the end of 2023 were searched and screened in the Web of Science Core Collection. They were analyzed and visualized using CiteSpace and the Bibliometric online analysis platform in terms of country, institution, author, journal, cited references, and keywords. In total, 619 publications from 522 journals with 682 authors from 42 countries were screened. The country with the highest number of publications is China ( = 445, 71.890%), followed by the United States ( = 60, 9.693%). The research institution with the highest number of publications is Shanghai Jiao Tong University ( = 42, 6.785%). The author with the highest number of publications is Cai, Zhengdong ( = 7), while the most cited author is Mizushimma N ( = 93). Among many journals, AUTOPHAGY has the most citations ( = 342), while CANCER LETT shows the greatest centrality (Centrality = 0.05). "Autophagy" is the most cited keyword ( = 177), and the keyword with the largest burst intensity is "cancer cells" (Strength = 6.27), which lasted from 2011 to 2014. China is a major contributor to autophagy research in the field of osteosarcoma, followed by the United States. All publications are in high-quality journals. "Autophagy" is a hot research topic in this field.
Manouchehri JM, Datta J, Marcho LM
… +10 more, Stover D, Ganju RK, Ramaswamy B, Carson WE, Mittra A, Zhang X, Schnell PM, Yue Y, Rubinstein MP, Cherian MA
Cancer Biol Ther
· 2025 Dec · PMID 40140347
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The highest incidence and cancer-related mortality rate among women worldwide is due to breast cancer. Triple-negative breast cancers (TNBC) are associated with more inferior outcomes than other breast cancers because of...The highest incidence and cancer-related mortality rate among women worldwide is due to breast cancer. Triple-negative breast cancers (TNBC) are associated with more inferior outcomes than other breast cancers because of their progressive nature and the deficit in available therapies. Therefore, there is a need for new therapeutic approaches. Our lab determined that chemotherapy induces the release of extracellular adenosine triphosphate (eATP), and, hence, augments TNBC cells' response to chemotherapy. Despite this, eATP concentrations are restricted by a variety of extracellular ATPases. We propose that, as an ATPase inhibitor, heparan sulfate (HS) would augment eATP concentrations and TNBC vulnerability induced by chemotherapy. Sulfatase 2 (SULF2) removes sulfate from HS, the functional group essential for ATPase inhibition. Consequently, we propose that TNBC cell death and eATP release induced by chemotherapy would be intensified by SULF2 inhibitors. We examined eATP and cell viability in paclitaxel-treated TNBC and nontumorigenic immortal mammary epithelial MCF-10A cells in the presence of OKN-007, a selective SULF2 inhibitor, and/or heparan sodium sulfate. Furthermore, sulfatase 1 (SULF1) and SULF2 protein expressions were ascertained. We found that the expression of SULF2 was greater in TNBC cell lines when compared to MCF-10A cells. The release of eATP and loss of TNBC cell viability induced by chemotherapy was enhanced by OKN-007. The co-treatment of chemotherapy and OKN-007 also attenuated cancer-initiating cells. This data implies that the combination of SULF2 inhibitors with chemotherapy augments eATP and decreases cell viability of TNBC greater than chemotherapy alone.
Cancer Biol Ther
· 2025 Dec · PMID 40089851
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Nearly 20 million people are diagnosed with cancer each year with breast cancer being the most common among women. Triple negative breast cancer (TNBC), defined by its no/low expression of ER and PR and lack of amplifica...Nearly 20 million people are diagnosed with cancer each year with breast cancer being the most common among women. Triple negative breast cancer (TNBC), defined by its no/low expression of ER and PR and lack of amplification of HER2, makes up 15-20% of all breast cancer cases. While patients overall have a higher response to chemotherapy, this subgroup is associated with the lowest survival rate indicating significant clinical and molecular heterogeneity demanding alternate treatment options. Therefore, new therapies have been explored, with a large focus on utilizing the immune system. A whole host of immunotherapies have been studied including immune checkpoint inhibitors, now standard of care for eligible patients, and possibly the most exciting and promising is that of a TNBC vaccine. While currently there are no approved TNBC vaccines, this review highlights many promising studies and points to an antigen, p53, which we believe is highly relevant for TNBC.
Cancer Biol Ther
· 2025 Dec · PMID 40081967
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, which encodes mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M), is upregulated in various cancers. We demonstrated high expression of PEPCK-M in approximately half of triple-negative breast cancers (TNBCs) pre..., which encodes mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M), is upregulated in various cancers. We demonstrated high expression of PEPCK-M in approximately half of triple-negative breast cancers (TNBCs) previously. TNBC is associated with an aggressive phenotype and a high metastasis rate. In this study, we investigated the role of in TNBC. knockdown suppressed proliferation and mTOR signaling in TNBC cells. In addition, cell invasion/migration ability and the expression of epithelial-to-mesenchymal transition (EMT) markers were positively correlated with expression in TNBC cells via regulation of transforming growth factor-β (TGF-β)/SMAD3 signaling. was positively regulated by in TNBC cells. Knockdown of in -overexpressing TNBC cells reduced the expression levels of EMT markers, Snail and Slug, and suppressed cell invasion/migration. In addition, knockdown attenuated the stimulatory effect of TGF-β on SMAD3 phosphorylation in TNBC cells. PEPCK-M promotes the protein and mRNA expression of SMAD3 via competitive binding to tripartite motif-containing 67 (TRIM67), an E3 ubiquitin ligase, to reduce SMAD3 ubiquitination, which leads to promoting nuclear translocation of SMAD3 and autoregulation of SMAD3 transcription. Moreover, high mRNA expression was significantly associated with poor survival in TNBC patients. In conclusion, our study revealed for the first time that activates TGF-β/SMAD3 signaling by regulating the expression and phosphorylation of SMAD3 by inhibiting TRIM67-mediated SMAD3 ubiquitination and promoting the stimulatory effect of TGF-β to promote TNBC invasion. The regulatory effect of on mTOR and TGF-β/SMAD3 signaling suggests that is a potential therapeutic target for suppressing TNBC progression.
Noreen S, Ishaq I, Saleem MH
… +3 more, Ali B, Muhammad Ali S, Iqbal J
Cancer Biol Ther
· 2025 Dec · PMID 40079211
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Early and precise diagnosis of cancer is pivotal for effective therapeutic intervention. Traditional diagnostic methods, despite their reliability, often face limitations such as invasiveness, high costs, labor-intensive...Early and precise diagnosis of cancer is pivotal for effective therapeutic intervention. Traditional diagnostic methods, despite their reliability, often face limitations such as invasiveness, high costs, labor-intensive procedures, extended processing times, and reduced sensitivity for early-stage detection. Electrochemical biosensing is a revolutionary method that provides rapid, cost-effective, and highly sensitive detection of cancer biomarkers. This review discusses the use of electrochemical detection in biosensors to provide real-time insights into disease-specific molecular interactions, focusing on target recognition and signal generation mechanisms. Furthermore, the superior efficacy of electrochemical biosensors compared to conventional techniques is explored, particularly in their ability to detect cancer biomarkers with enhanced specificity and sensitivity. Advancements in electrode materials and nanostructured designs, integrating nanotechnology, microfluidics, and artificial intelligence, have the potential to overcome biological interferences and scale for clinical use. Research and innovation in oncology diagnostics hold potential for personalized medicine, despite challenges in commercial viability and real-world application.
Zhong L, Zhu J, Chen J
… +5 more, Jin X, Liu L, Ji S, Luo J, Wang H
Cancer Biol Ther
· 2025 Dec · PMID 40069131
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Breast cancer remains a global health challenge with varied prognoses despite treatment advancements. Therefore, this study explores the pseudogene MGAT4EP as a potential biomarker and therapeutic target in breast cancer...Breast cancer remains a global health challenge with varied prognoses despite treatment advancements. Therefore, this study explores the pseudogene MGAT4EP as a potential biomarker and therapeutic target in breast cancer. Using TCGA data and bioinformatics, MGAT4EP was identified as significantly overexpressed in breast cancer tissues and associated with poor prognosis. Multivariate Cox regression confirmed MGAT4EP as important prognostic factor. A clinical prediction model based on MGAT4EP expression showed high accuracy for 1-, 3-, and 5-year survival rates and was translated into a nomogram for clinical application. Functional studies revealed that silencing MGAT4EP siRNA promoted apoptosis, inhibited migration and invasion in breast cancer cells. RNA-seq, GSEA, and GO analyses linked MGAT4EP to apoptosis and focal adhesion pathways. Notably, knock down of MGAT4EP significantly suppressed tumor growth and metastasis in xenograft and lung metastasis models. Taken together, these findings establish MGAT4EP as an attractive target for metastatic breast cancer and provide a potential a promising therapeutic target for breast cancer treatment.
Tian R, Song H, Li J
… +5 more, Yuan T, Liu J, Wang Y, Li Y, Song X
Cancer Biol Ther
· 2025 Dec · PMID 40065703
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PURPOSE: Abnormal expression of PINCH-1 has been observed in various types of human cancers. However, the clinical importance and mechanism underlying its role in head and neck squamous cell carcinoma (HNSCC) is yet to b...PURPOSE: Abnormal expression of PINCH-1 has been observed in various types of human cancers. However, the clinical importance and mechanism underlying its role in head and neck squamous cell carcinoma (HNSCC) is yet to be fully elucidated. METHODS: This study evaluated the expression of PINCH-1 in HNSCC samples through immunohistochemical staining and Western blotting. AMC-HN-8, Cal27, and SCC7 cell lines were utilized for cellular function experiments, both in vivo and in vitro. CCK8, colony-formation assay, flow cytometry, wound-healing assay, and transwell assay were employed to investigate the effects of alterations in target proteins on the growth and metastasis of cancer cells. Mito-Tracker Deep Red FM was used to track mitochondrial morphology. RESULTS: PINCH-1 was found to be overexpressed in HNSCC and closely associated with lymph node metastasis and poor pathologic differentiation. Its upregulation promoted proliferation, inhibited apoptosis, and enhanced migration and invasion in HNSCC cells. It also promoted mitochondrial fission. We conducted a mechanism analysis, which showed that PINCH-1 knockdown inhibited mitochondrial fission by reducing the expression of DRP1. Furthermore, inhibition of mitochondrial fission could impede the proliferation and metastasis of HNSCC cells. Re-expression of DRP1 reversed the inhibitory effect of PINCH-1 knockdown on mitochondrial fission, cell proliferation, and metastasis in HNSCC cells. CONCLUSIONS: PINCH-1 plays a critical oncogenic role in HNSCC by enhancing DRP1-mediated mitochondrial fission, which may serve as a novel therapeutic target for HNSCC.
Cancer Biol Ther
· 2025 Dec · PMID 40018990
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Our study aims to investigate the roles of embryonic lethal abnormal vision-like 1 (ELAVL1) and long non-coding RNA (LncRNA) NEAT1 in endometrial cancer (EC), focusing on their underlying molecular mechanisms.We obtained...Our study aims to investigate the roles of embryonic lethal abnormal vision-like 1 (ELAVL1) and long non-coding RNA (LncRNA) NEAT1 in endometrial cancer (EC), focusing on their underlying molecular mechanisms.We obtained EC cell lines (HEC-1A, Ishikawa, RL95-2, HEC-1B, and AN3CA) from ATCC. We used siRNAs (si-ELAVL1#1 and si-ELAVL1#2) and overexpression RNAs (OE ELAVL1 and OE-NEAT1) for knockdown or overexpression of ELAVL1 and LncRNA NEAT1. We also employed 3-MA (5mM) or rapamycin (100µM) to inhibit or promote autophagy. Moreover, we conducted RNA immunoprecipitation (RIP) assays to confirm the interaction between LncRNA NEAT1 and ELAVL1. Cell Counting Kit-8 (CCK-8) and transwell assays were utilized to assess cell proliferation and migration. Additionally, we measured the expression of ELAVL1 and Beclin1 through Western blotting and RT-qPCR.ELAVL1 was found to be highly expressed in EC. Furthermore, ELAVL1 promoted the proliferation, invasion, and migration of EC cells through the regulation of Beclin1-related pathways. RIP assays revealed a direct interaction between LncRNA NEAT1 and ELAVL1, with ELAVL1 stabilizing LncRNA NEAT1 mRNA in EC cells. Additionally, we observed that ELAVL1 influenced EC cell proliferation, invasion, and migration through the regulation of LncRNA NEAT1-mediated regulation of Beclin1 expression. Moreover, in an animal study, we determined that ELAVL1 influenced endometrial cancer tumor growth through its interaction with LncRNA NEAT1, which mediated Beclin1 expression in vivo.In summary, our study showed that ELAVL1 regulated the malignant behavior of endometrial cancer cells through the modulation of LncRNA NEAT1-mediated regulation of Beclin1 expression.
Cancer Biol Ther
· 2025 Dec · PMID 39992057
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CXC Chemokine receptor type 4 (CXCR4) is commonly considered a potential marker for cancer stem cells (CSCs). Dedifferentiated-type chordoma (DTC) cells derived from a patient with recurrent chordoma exhibit high CXCR4 e...CXC Chemokine receptor type 4 (CXCR4) is commonly considered a potential marker for cancer stem cells (CSCs). Dedifferentiated-type chordoma (DTC) cells derived from a patient with recurrent chordoma exhibit high CXCR4 expression and demonstrate increased resistance to chemotherapeutic drugs and ionizing radiation (IR) compared to the conventional-type chordoma cell line, U-CH1. However, the precise role of CXCR4 in the stemness and IR resistance of DTC remains unclear. Therefore, this study aims to elucidate the correlation between the expression of CXCR4 and stemness and radioresistance in chordoma. DTC cells expressing CXCR4 (CXCR4 DTC cells), isolated by magnetic-activated cell sorting, exhibited increased self-renewal activity, tumorigenicity, and IR resistance, accompanied by elevated Sox2 expression. Knockdown of CXCR4 expression using short hairpin RNA, inhibition of CXCR4 signaling with AMD3100, and targeting of STAT3, a downstream effector of CXCR4, with WP1066 in DTC cells significantly diminished their self-renewal ability, tumorigenic potential, IR resistance, and Sox2 expression. Additionally, transfection with a small interfering Sox2 RNA suppressed self-renewal activity, tumorigenicity, and IR resistance in DTC cells, whereas overexpression of CXCR4 reversed these effects in U-CH1 cells. Furthermore, DTC cells infected with shCXCR4 exhibited substantial tumor suppression, and the combination of IR and AMD3100 significantly reduced DTC tumor growth in a mouse xenograft model. These findings underscore the functional significance of CXCR4 as a CSC marker, highlighting its potential as a therapeutic target for malignant chordomas.