Chaowen Xiao, Xinyang Zhao, Zouxiao Hu, Guanbao Long
{"title":"MFSD2A Overexpression Inhibits Hepatocellular Carcinoma Through TGF-β/Smad Signaling.","authors":"Chaowen Xiao, Xinyang Zhao, Zouxiao Hu, Guanbao Long","doi":"10.1002/mc.23875","DOIUrl":"10.1002/mc.23875","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a common primary malignancy of the liver and has a high mortality. Major facilitator superfamily domain containing 2 (MFSD2A) was previously demonstrated to inhibit tumor progression in several cancers. Here, we elucidated the association between MFSD2A expression and HCC progression and also investigated the underlying mechanism. The online tools were utilized to evaluate MFSD2A expression in HCC samples and predict the prognostic significance of MFSD2A in HCC patients. The biological role of MFSD2A in HCC cellular processes was examined by colony formation, wound healing, transwell, and western blotting. The in vivo role of MFSD2A in HCC was investigated in a xenograft tumor model. The miRNAs and RNA-binding proteins potentially targeting MFSD2A were identified using bioinformatics prediction tools. Luciferase reporter, RNA immunoprecipitation, actinomycin D, and immunofluorescence assays were performed to investigate the molecule mechanisms of MFSD2A. Transforming growth factor (TGF)-β1/Small mothers against decapentaplegic (Smad) signaling was detected using western blot analysis. We found that MFSD2A expression was significantly downregulated in HCC patients and cells and its downregulation predicted a poor prognosis. MFSD2A overexpression repressed HCC cell proliferation, migration, invasion, the epithelial-to-mesenchymal transition in vitro, as well as inhibited HCC tumor growth in vivo. MFSD2A was targeted by miR-3189-3p. High-density lipoprotein binding protein (HDLBP) inhibited MFSD2A expression by binding to and destabilizing MFSD2A mRNA. MFSD2A significantly suppressed activation of TGF-β/Smad signaling in HCC cells. Knockdown of MFSD2A abrogated the inhibitory effect of miR-3189-3p inhibitor on HCC cellular processes, and overexpression of MFSD2A reversed the tumor-promoting effect of HDLBP overexpression. Overall, MFSD2A exerts a tumor-inhibiting effect in HCC via suppression of TGF-β/Smad signaling, suggesting that MFSD2A may be a promising target for HCC therapy.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":"64 3","pages":"597-611"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrative Bioinformatics Analysis and Experimental Study of NLRP12 Reveal Its Prognostic Value and Potential Functions in Ovarian Cancer.","authors":"Zhihui Xie, Tiantian Yang, Chuchu Zhou, Zixin Xue, Jianjun Wang, Feng Lu","doi":"10.1002/mc.23854","DOIUrl":"10.1002/mc.23854","url":null,"abstract":"<p><p>NLRP12 plays a significant role in cellular functional behavior and immune homeostasis, influencing inflammation, tumorigenesis, and prognosis. This study aimed to explore its specific effects on the tumor microenvironment (TME) and its contribution to heterogeneity in ovarian cancer (OV) through bioinformatics analysis and experimental verification. Utilizing various bioinformatics databases and clinical specimens, we investigated NLRP12 expression and its relationship with OV prognosis and immune infiltration. In vitro assays were conducted to assess the impact of NLRP12 on the proliferation and invasion of OV cells. Our findings indicate that NLRP12 is upregulated in OV, with high expression correlating with a negative prognosis. Furthermore, NLRP12 expression demonstrated a positive correlation with the infiltration of various immune cells and the expression of immune checkpoint molecules in OV. Analysis of The Cancer Immunome Atlas (TCIA) database revealed that OV patients with lower NLRP12 expression may exhibit an enhanced response to immunotherapy, particularly CTLA4 blockers, a finding validated in animal experiments. Additionally, the study emphasized the role of NLRP12 in influencing the prognosis of OV patients by promoting epithelial-mesenchymal transition (EMT) in ovarian cancer cells. Finally, we identified a potential therapeutic compound, Schisandrin B (Schi B), which decreases NLRP12 expression in ovarian cancer cells by binding to the transcription factor SPI1 associated with NLRP12. Our findings suggest that NLRP12 serves as a crucial immune-related biomarker predicting poor outcomes in OV, and targeting NLRP12 may represent a promising therapeutic approach for OV patients in the future.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"383-398"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142730674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanjie Xu, Ke Xie, Ling Li, Zhong Li, Qicheng Lu, Jin Feng
{"title":"FOXN3 Downregulation in Colorectal Cancer Enhances Tumor Cell Stemness by Promoting EP300-Mediated Epigenetic Upregulation of SOX12.","authors":"Yanjie Xu, Ke Xie, Ling Li, Zhong Li, Qicheng Lu, Jin Feng","doi":"10.1002/mc.23852","DOIUrl":"10.1002/mc.23852","url":null,"abstract":"<p><p>Cancer stemness plays a crucial role in promoting the progression of colorectal cancer (CRC). Forkhead box N3 (FOXN3) is a tumor suppressor protein. Herein, we investigated the role of FOXN3 in the regulation of CRC cell stemness. Cell viability, proliferation, migration, and invasion were assessed utilizing cell counting kit-8 assay, 5-ethynyl-20-deoxyuridine assay, and Transwell assay, respectively. Cell-sphere formation was assessed using a sphere-forming assay. The enrichment of H3K27ac modifications at the SRY-related HMG-box 12 (SOX12) promoter, interactions among FOXN3, SOX12, and E1A binding protein p300 (EP300) were analyzed using chromatin immunoprecipitation or dual luciferase reporter assays. We found that FOXN3 overexpression inhibited CRC cell proliferation, migration, invasion, stemness, and tumor formation in mice by inactivating the Wnt/β-catenin signaling, while these effects of FOXN3 overexpression were reversed by the overexpression of SOX12. Mechanistically, EP300 increased SOX12 expression in CRC cells by promoting H3K27ac enrichment in the SOX12 promoter. In addition, FOXN3 transcriptionally inhibited EP300 expression in CRC cells by binding to the EP300 promoter. As expected, EP300 overexpression weakened the inhibitory effect of FOXN3 overexpression on CRC cell stemness. Collectively, FOXN3 upregulation inhibited CRC cell stemness by suppressing EP300-mediated epigenetic upregulation of SOX12.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"410-424"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Effect of Gender on the Intestinal Flora of Colorectal Cancer Under Different Stages.","authors":"Fuhai He, Xiaoliang Huang, Zhen Wang, Mingjian Qin, Chuanbin Chen, Zigui Huang, Yongzhi Wu, Yongqi Huang, Binzhe Tang, Chenyan Long, Xianwei Mo, Weizhong Tang, Jungang Liu","doi":"10.1002/mc.23863","DOIUrl":"10.1002/mc.23863","url":null,"abstract":"<p><p>This study aims to determine whether gender is a factor in the interplay between the human intestinal flora and colorectal cancer (CRC), ultimately providing new evidence for the clinical prediction and management of CRC in different genders. In this study, we included 186 untreated CRC patients, and classified them into two groups based on pathological staging: Groups Ⅰ-Ⅱ and Groups Ⅲ-Ⅳ, with male and female groups within each group. We collected preoperative fecal samples from these patients and performed 16S rRNA gene sequencing to analyze their intestinal flora. In the CRC Stages I-II cohort, the gut microbiota of the female group exhibited greater diversity and abundance compared to the male group, with a total of 13 gut microbiota demonstrating significant disparities. Notably, s__Parabacteroides gordonii, s__Bacteroides faecis, and s__Bacteroides nordii were found to be more prevalent in the female group relative to the male group. Within the CRC Stages III-IV cohort, 51 gut microbiota exhibited significant differences between the genders. In the immunocyte composition of fecal samples from patients with CRC, a higher proportion of naive B cells is observed in the male group as compared to the female group. In female CRC patients within the CRC Stages III-IV cohort, Actinomyces exhibited a significant negative correlation with activated dendritic cells, CD4+ memory T cells, and eosinophils. In male CRC patients within the CRC Stages III-IV cohort, Actinomyces demonstrated a significant positive correlation with naive B cells and a significant positive correlation with immune activation genes TNFRSF25 and TMIGD2. In female CRC patients within the CRC Stages III-IV cohort, Actinomyces showed a significant negative correlation with activated dendritic cells, CD4+ memory T cells, and eosinophils, and a significant positive correlation with immune activation genes TNFSF13B, LTA, KLRK1, and CXCL12. In the CRC Stages I-II group, the female group's intestinal flora is more diverse and richer than the male group. In the CRC Stages III-IV group, there are a total of 51 different intestinal flora in both the male and female groups. We also found that Actinomyces affects the occurrence and development of CRC in the male and female groups through different pathways. The results show that the intestinal flora differs between male and female CRC patients and is closely associated with cancer development.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"526-542"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shu-Yi Yang, Jing-Siang Jhang, Wen-Long Huang, Leah H J Tsai, Min-Chia Tsai, Chin-Pui Chan, Ru-Inn Lin, Hon-Yi Lin, Chin Li, Chia-Chou Yeh, Michael W Y Chan
{"title":"Wogonin Inhibits Ovarian Cancer by Activating the AMPK-TET2-5hmC Axis.","authors":"Shu-Yi Yang, Jing-Siang Jhang, Wen-Long Huang, Leah H J Tsai, Min-Chia Tsai, Chin-Pui Chan, Ru-Inn Lin, Hon-Yi Lin, Chin Li, Chia-Chou Yeh, Michael W Y Chan","doi":"10.1002/mc.23856","DOIUrl":"10.1002/mc.23856","url":null,"abstract":"<p><p>Ovarian cancer is one of the most common gynecologic cancers. In the quest for effective anti-cancer agents, this study explores the effects of wogonin, a naturally occurring flavonoid, on the viability and migration of A2780 and Kuramochi ovarian cancer cells. A2780 and Kuramochi human ovarian cancer cell lines were utilized. Cytotoxicity and migration were evaluated using the CCK8 assay and the wound-healing assay, respectively. The effect of wogonin on the growth of A2780 ovarian cancer cells in vivo was assessed using a nude mouse model. The phosphorylation and half-life of AMPK were determined by western blot analysis. The level of 5hmC was assessed using dot blot analysis. The impact of wogonin on gene expression was examined through RNA-Seq. Our results show that wogonin not only impedes cancer cell growth and mobility both in vitro and in vivo but also significantly increases the cytotoxicity of cisplatin. Investigations of the mechanism underlying these effects reveal that wogonin suppresses genes associated with cell proliferation and the EMT and upregulates metabolic pathways, particularly the AMPK signaling pathway, which is crucial for increasing 5hmC levels. These results indicate that wogonin promotes DNA demethylation by stabilizing TET2. In conclusion, our findings highlight not only the therapeutic potential of wogonin but also its preventative capability against ovarian cancer in individuals with metabolic disorders, such as diabetes, who are at increased risk of ovarian cancer.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"440-449"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Yin, Zhigang Pei, Chunrong Wu, Jie Liu, Jianxiang Huang, Rui Xia, Debing Xiang
{"title":"M2 Macrophage-Derived Exosomal circ_0088494 Inhibits Ferroptosis via Promoting H3K4me1 Modification of STEAP3 in Cutaneous Squamous Cell Carcinoma.","authors":"Jun Yin, Zhigang Pei, Chunrong Wu, Jie Liu, Jianxiang Huang, Rui Xia, Debing Xiang","doi":"10.1002/mc.23862","DOIUrl":"10.1002/mc.23862","url":null,"abstract":"<p><p>Cutaneous squamous cell carcinoma (cSCC) is a common type of cutaneous cancer globally. M2 macrophage-derived exosomes (M2 exosomes) facilitate the development of cancer. Ferroptosis, a newly uncovered form of cell death, is linked to cancer progression. The present research planned to study the function and potential mechanism of M2 exosomes on ferroptosis in cSCC. Patients with cSCC were recruited to gather adjacent noncancerous specimens and cSCC tissues. Mononuclear macrophage (THP-1) cells were differentiated into M2 macrophages before exosome extraction, and then the exosomes were added into cSCC cells (A431 and SCL-1). Erastin was applied to induce ferroptosis. Cell viability, mitochondrial superoxide, lipid-ROS, malondialdehyde (MDA), and iron level were detected to validate ferroptosis in cSCC cells. Proteins and RNAs were tested by applying western blot and RT-qPCR. The combination between molecules was validated by ChIP and RIP. Six-transmembrane epithelial antigen of the prostate 3 (STEAP3) was elevated in cSCC specimens, which correlated to reduced ferroptosis. cSCC tissues presented an increase in the number of M2 macrophages. Erastin-elicited ferroptosis was repressed by M2 macrophages, while exosome inhibitor GW4869 neutralized the outcome of M2 macrophages. Furthermore, M2 exosomes repressed ferroptosis of cSCC cells via circ_0088494, which might be related to the upregulation of STEAP3. M2 exosomes-derived circ_0088494 promoted histone 3 lysine 4 monomethylation (H3K4me1) modification of STEAP3 by recruiting histone-lysine N-methyltransferase 2D (KMT2D). The effect of circ_0088494-silenced M2 exosomes on ferroptosis was antagonized by STEAP3 overexpression. M2 exosomes-derived circ_0088494 recruited KMT2D to promote H3K4me1 modification of STEAP3, thereby inhibiting ferroptosis in cSCC. This study might provide a novel target for cSCC treatment.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"513-525"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peng Chen, Hang Zhou, Xian Yang, Yuzhen Zheng, Yujie Chen, Peiyuan Wang, Hao He, Shuoyan Liu, Feng Wang
{"title":"A-to-I-Edited miR-1304-3p Inhibits Glycolysis and Tumor Growth of Esophageal Squamous Cell Carcinoma by Inactivating Wnt5a/ROR2 Signaling.","authors":"Peng Chen, Hang Zhou, Xian Yang, Yuzhen Zheng, Yujie Chen, Peiyuan Wang, Hao He, Shuoyan Liu, Feng Wang","doi":"10.1002/mc.23867","DOIUrl":"10.1002/mc.23867","url":null,"abstract":"<p><p>A-to-I RNA editing is a pervasive mechanism in the human genome that affects the regulation of gene expression and is closely associated with the pathogenesis of numerous diseases. This study elucidates the regulatory mechanism of A-to-I edited miR-1304-3p in esophageal squamous cell carcinoma (ESCC). Western blot, immunohistochemistry, and RT-qPCR assays were employed to quantify protein and mRNA expression. Colony formation, Edu, wound healing, and Transwell assays were applied to determine miRNA function. Glycolysis was assessed using glucose uptake and lactate production assay. A dual-luciferase reporter assay confirmed the downstream targets of miRNA, and a xenograft assay demonstrated the efficacy of the miRNA. The A-to-I RNA editing level of miR-1304-3p was observed to increase in KYSE180 and KYSE140 ESCC cells following ADAR1 treatment. Following A-to-I editing, the function of miR-1304-3p in ESCC progression underwent a reversal, shifting from carcinogenic to inhibitory. Wild-type (WT) miR-1304-3p targets IRS1, whereas the edited version targets ROR2. The WT miR-1304-3p, but not the edited version, suppressed the expression and tumor-suppressive effect of IRS1 in ESCC. Conversely, ROR2, a specific downstream target of the edited miR-1304-3p, acted as a tumor promoter in ESCC. Furthermore, A-to-I editing of miR-1304-3p can inhibit glycolysis and inactivate the Wnt5a/ROR2 signaling pathway in ESCC. A-to-I RNA editing alters the function of miR-1304-3p in ESCC by changing its target gene. The edited miR-1304-3p hinders the development of ESCC by inhibiting glycolysis and inactivating the Wnt5a/ROR2 signaling pathway.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":"64 3","pages":"552-564"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"mRNA m5C Alteration in Azacitidine Demethylation Treatment of Acute Myeloid Leukemia.","authors":"Ziwei Chen, Yingyu Guo, Zaifeng Zhang, Chang Li, Lili Zhang, Ye Liu, Gaoyuan Sun, Fei Xiao, Ru Feng, Chunli Zhang","doi":"10.1002/mc.23864","DOIUrl":"10.1002/mc.23864","url":null,"abstract":"<p><p>The DNA demethylating therapy with azacitidine (AZA) is a promising therapeutic strategy for elderly patients with acute myeloid leukemia (AML). AZA primarily inhibits DNA methylation, promotes cell differentiation and apoptosis in AML. However, as a cytosine nucleoside analog, AZA also has the potential to be incorporated into RNA molecules. To assess the impact of AZA on RNA m5C methylation during demethylating therapy, we conducted Nanopore direct-RNA sequencing on samples from three AML patients pre and after demethylating therapy, as well as on HL-60 cells pretreated with AZA. We performed an integrated analysis of the transcriptome and the m5C methylome, contrasting the states of complete remission with those of active disease (AML). Our results revealed an extensive demethylation effect at the RNA level attributable to AZA and found that mRNA m5C modification may play a pivotal role in the progression of AML. Additionally, S100P was identified as a biomarker with significant prognostic implications. We also conducted a conjoint analysis of the transcriptome and the m5C methylome of the full-length transcripts, uncovering several dysregulated mRNA isoforms. Collectively, our findings indicate that mRNA m5C methylation is implicated during AML progression, and AZA exhibits an overall suppressive effect on this process.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"502-512"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Chen, Qihui Sun, Qi Zou, Xiaoqi Zhu, Tingting Wen, Xiaojia Li, Shu Li, Jie He, Fang Wei, Keping Xie
{"title":"FOXM1-Cx31 Axis Drives Pancreatic Cancer Stem Cell-Like Properties and Chemoresistance.","authors":"Yang Chen, Qihui Sun, Qi Zou, Xiaoqi Zhu, Tingting Wen, Xiaojia Li, Shu Li, Jie He, Fang Wei, Keping Xie","doi":"10.1002/mc.23870","DOIUrl":"10.1002/mc.23870","url":null,"abstract":"<p><p>Pancreatic cancer is a highly lethal malignancy with few effective treatment options. Connexin 31 (Cx31) is a membrane protein capable of forming hexameric channels to facilitate the exchange of metabolites and signaling molecules. Yet, the contribution of Cx31 to the onset and progression of pancreatic cancer remains to be understood. We analyzed Cx31 expression in pancreatic cancer tissues and cell lines using public databases and experimental models. The correlation between Cx31 expression and clinical outcomes was evaluated. The effects of Cx31 on pancreatic cancer cell proliferation, stemness, migration, chemoresistance, and immune infiltration were investigated. Transcriptome analysis and bioinformatics tools were employed to explore the underlying mechanisms. Cx31 was found to be upregulated in pancreatic cancer tissues compared to normal tissues, and its high expression correlated with shorter overall survival and higher mortality risk. Cx31 promoted acinar-to-ductal metaplasia (ADM), stemness, proliferation, migration, metastasis, and chemoresistance in pancreatic cancer cells. Bioinformatics analysis suggested a positive correlation between Cx31 and stemness-related genes. Cx31 knockdown altered the expression of genes involved in stemness and chemoresistance pathways, such as Wnt and Notch. Additionally, Cx31 was identified as a direct target of the transcription factor FOXM1, which upregulated its expression. Cx31 plays a multifaceted role in pancreatic cancer, influencing processes from initiation to metastasis and chemoresistance. It may serve as a potential therapeutic target to combat the aggressive nature of pancreatic cancer. The FOXM1-Cx31 axis could be a promising target for overcoming treatment resistance in pancreatic cancer.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"565-579"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yali Zhao, Yan He, Zhiyuan Xiao, Le Xin, Mingjing Deng, Mingxia Yao, Guan Huang
{"title":"circEIF3I Promotes Colorectal Cancer Metastasis by Regulating the miR-328-3p/NCAPH Axis.","authors":"Yali Zhao, Yan He, Zhiyuan Xiao, Le Xin, Mingjing Deng, Mingxia Yao, Guan Huang","doi":"10.1002/mc.23860","DOIUrl":"10.1002/mc.23860","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the most common gastrointestinal malignancy, with its recurrence and metastasis significantly affecting patient survival. Circular RNAs (circRNAs), a novel class of noncoding RNAs, have emerged as crucial contributors to CRC pathogenesis. However, the role of circEIF3I in CRC metastasis remains unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to assess circEIF3I, microRNA (miR)-328-3p, and NCAPH expression. CRC cell migration and invasion were determined via Transwell assays. Western blot analysis was utilized to define the protein expression of epithelial-mesenchymal transition (EMT) markers and NCAPH. Xenograft tumor was established for exploration into the function of circEIF3I in CRC metastasis to the liver and lung. The binding between miR-328-3p and circEIF3I or NCAPH was predicted through ENCORI or TargetScan platform and ascertained through dual-luciferase reporter assays. circEIF3I and NCAPH expression were found to be elevated in CRC tissues and cells, while miR-328-3p was downregulated. Functionally, circEIF3I knockdown inhibited CRC cell migration, invasion, EMT, and tumor metastasis. Mechanistic analyses revealed that circEIF3I can target miR-328-3p, while NCAPH was targeted by miR-328-3p. Furthermore, circEIF3I facilitated NCAPH expression in CRC cells by sequestering miR-328-3p. Notably, miR-328-3p inhibitor or NCAPH overexpression negated the effects of circEIF3I knockdown on preventing CRC progression in vitro. Taken together, circEIF3I elevated NCAPH expression by sponging miR-328-3p, thereby promoting CRC metastasis. These findings suggest that the circEIF3I/miR-328-3p/NCAPH axis represents a novel therapeutic target for CRC.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"450-462"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}