Molecular Carcinogenesis最新文献

{"title":"METTL1 Enhances RRP9 mRNA Stability Through m7G Modification to Drive Colorectal Tumorigenesis.","authors":"Nan Li, Ying Jing, Long Xu, Maonan Wang","doi":"10.1002/mc.23892","DOIUrl":"10.1002/mc.23892","url":null,"abstract":"<p><p>METTL1, a well-established RNA methyltransferase for the N(7)-methylguanosine (m7G) methylation modification, is responsible for human tumorigenesis. Here, we aimed to examine the activity and molecular determinants of METTL1 in colorectal cancer (CRC) development. METTL1 and ribosomal RNA processing 9 (RRP9) mRNA analysis was performed by quantitative PCR. Protein expression was detected by immunoblotting and immunohistochemistry (IHC). Cell sphere formation, invasion, and proliferation were assessed by sphere formation, transwell, and MTT assays, respectively. Cell migration was tested by transwell and wound healing assays. Subcutaneous xenografts were produced to analyze the role in vivo. The influence of METTL1 in m7G methylation and stability of RRP9 mRNA was evaluated by methylated immunoprecipitation (MeRIP) assay and Actinomycin D (Act D) treatment, respectively. METTL1 was highly expressed in CRC tumors and cell lines. METTL1 depletion suppressed CRC cell proliferation, invasiveness, migratory ability, and sphere formation potential in vitro, while increased METTL1 expression had opposite effects. METTL1 positively correlated with RRP9 expression in CRC. Mechanistically, METTL1 promoted RRP9 mRNA stability by mediating its m7G methylation, and METTL1 regulated the PI3K/AKT signaling by RRP9. Increased RRP9 expression partially reversed the suppressive effects of METTL1 depletion on CRC cell phenotypes in vitro. METTL1 depletion impeded the growth of HCT-116 subcutaneous xenografts in vivo by RRP9. Our observations identified METTL1 as a crucial protumorigenic factor to drive growth, metastasis, and stemness of CRC cells through RRP9, offering new targets for combating CRC.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"858-869"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440512","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":"CircST6GALNAC6 Inhibits Glycolysis of Bladder Cancer by Regulating PRKN/HK1 Signaling Pathway.","authors":"Yali Zuo, Da Ren, Haiqing He, Changkun Huang, Xuan Zhu","doi":"10.1002/mc.23894","DOIUrl":"10.1002/mc.23894","url":null,"abstract":"<p><p>Bladder cancer (BCa) is an aggressive malignancy of urinary system. Aerobic glycolysis refers to the phenomenon wherein cancer cells increase glucose consumption and produce lactic acid. Our study focused on the role and mechanism of circST6GALNAC6 in BCa glycolysis. The 24 h glucose intake was detected using flow cytometry. Lactic acid and ATP were detected in BCa cells utilizing commercially provided kits. Extracellular acidification rate was measured using Seahorse XF-96p Extracellular Flux Analyzer. Cell proliferation was determined using colony formation assay. RNA immunoprecipitation and co-immunoprecipitation experiments were adopted to validate molecular interactions. BALB/C nude mice were utilized to establish xenograft tumor model. CircST6GALNAC6 was decreased in BCa cells, and overexpression of circST6GALNAC6 inhibited glycolysis and proliferation of BCa cells. Additionally, overexpression of circST6GALNAC6 promoted the degradation of glycolytic regulatory protein HK1 and decreased its expression, and PRKN facilitated ubiquitination-related degradation of HK1. CircST6GALNAC6 enhanced the mRNA stability and expression of PRKN by recruiting FUS. Furthermore, the inhibitory impact of circST6GALNAC6 overexpression on glycolysis in BCa cells was reversed by PRKN knockdown. Finally, overexpression of circST6GALNAC6 suppressed tumor growth through increasing PRKN in nude mice. CircST6GALNAC6 suppressed glycolysis in BCa through FUS/PRKN/HK1 axis. Targeting circST6GALNAC6 holds promise as a novel approach for treating BCa.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"870-882"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441531","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":"Integrated Genomics Reveal Potential Resistance Mechanisms of PANoptosis-Associated Genes in Acute Myeloid Leukemia.","authors":"Cong Liang, Zhiqing Long, Mengjie Lei, Ran Ding, Mengke Chen","doi":"10.1002/mc.23886","DOIUrl":"10.1002/mc.23886","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is marked by the proliferation of abnormal myeloid progenitor cells in the bone marrow and blood, leading to low cure rates despite new drug approvals from 2017 to 2018. Current therapies often fail due to the emergence of drug resistance mechanisms, such as those involving anti-apoptotic pathways and immune evasion, highlighting an urgent need for novel approaches to overcome these limitations. Programmed cell death (PCD) is crucial for tissue homeostasis, with PANoptosis-a form of PCD integrating pyroptosis, apoptosis, and necroptosis-recently identified. This process, regulated by the PANoptosome complex, could be key to overcoming AML drug resistance. Targeting multiple PCD pathways simultaneously may prove more effective than single-target therapies. Research suggests that disrupting anti-apoptotic mechanisms, such as those involving Bcl-2, can enhance drug sensitivity in AML. This study hypothesizes that PANoptosis-associated resistance genes (PARGs) play a critical role in AML drug resistance by modulating immune responses and offers a multi-faceted approach to tackle this challenge. Using RNA sequencing data from the Cancer Genome Atlas and Gene Expression Omnibus databases, we performed differential expression analysis to identify significantly dysregulated PARGs in AML. Regression analysis identified prognostic PARGs, bridging a key gap in understanding how these genes contribute to treatment resistance. We then verified their expression in AML cell lines and cell samples treated with cytarabine using RT-qPCR. Hierarchical clustering revealed distinct PARG expression patterns, and functional enrichment analysis highlighted their involvement in immune-related pathways. The combination of bioinformatics and experimental validation underscores how these genes may mediate immune modulation in drug resistance, providing a robust framework for further study. Our findings suggest that PARGs contribute to AML resistance by modulating immune responses and provide potential targets for therapeutic intervention. This study highlights the potential of targeting PARGs to improve treatment outcomes in AML. By analyzing the expression changes of these genes in response to standard clinical treatments, we provide a framework for developing multi-target therapeutic strategies that simultaneously disrupt multiple programmed cell death pathways. Such an approach directly addresses the limitations of current treatments by offering a method to enhance drug sensitivity and mitigate resistance, potentially improving survival rates. Our findings underscore the importance of a comprehensive understanding of PCD mechanisms and pave the way for innovative treatments that could significantly impact AML management.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"801-815"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046938","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":"Correction to \"Plasma DNA Methylation-Based Biomarkers for MPNST Detection in Patients With Neurofibromatosis Type 1\".","authors":"","doi":"10.1002/mc.23890","DOIUrl":"10.1002/mc.23890","url":null,"abstract":"","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"953"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657753","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":"Identification of Interleukin-Related Genes Signature for Prognosis Prediction in Head and Neck Squamous Cell Carcinoma Patients.","authors":"Haojie Yang, Zihao Liu, Zicong Tan, Huimin Luo, Qin Li, Zhongqi Liu, Fengtao Ji","doi":"10.1002/mc.23880","DOIUrl":"10.1002/mc.23880","url":null,"abstract":"<p><p>This study focused on identifying the interleukin (IL)-related genes that influence the head and neck squamous cell carcinoma (HNSCC) patients' prognosis and response to anticancer therapy in patients with HNSCC. We developed a risk model that included three gene signatures, IL Enhancer Binding Factor 2 (ILF2), IL 36 alpha (IL36A), and IL10, based on differential expression analysis, survival analysis, Least Absolute Shrinkage and Selection Operator (LASSO) analysis, and Cox regression analysis. We found that the low-risk group was scored with higher immune cell infiltration, higher expression of human leukocyte antigen (HLA) family genes and immune checkpoint genes, higher cytolytic activity (CYT), tertiary lymphoid structures (TLS), and CD8A/PD-L1 ratio. In contrast, the high-risk group was scored with higher tumor immune dysfunction and exclusion (TIDE), which implied worse response to immunotherapy and worse prognosis. The results above indicated that the low-risk group had stronger antitumor immunity and better responsiveness to immunotherapy. We also observed a significantly enriched pattern of cancer-related pathways and immune pathways in the comparison of the high-risk and low-risk groups. Furthermore, the high-risk group had higher sensitivity to chemotherapy drugs, which suggested that they might benefit from chemotherapy treatment. Following the results above, we confirmed in HNSCC cell lines and clinical specimens that the level of ILF2 in tumors was significantly higher than that in adjacent tumor tissues. Besides, in vivo and in vitro results both showed that silencing ILF2 might depress tumor growth, invasion, and migration. This study not only provided novel perspectives into the immunological and molecular mechanisms of HNSCC and uncovered IL-related gene signatures for predicting HNSCC patients' prognosis and response to chemotherapy and immunotherapy, but also preliminarily suggested that ILF2 might be an important target in the treatment of HNSCC.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"842-857"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365271","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":"Knocking Down Ferredoxin 1 Inhibits the Progression of Colorectal Cancer and Regulates Cuproptosis via Mediating the Hippo Signaling Pathway.","authors":"Ying Hu, Haihua Liu, Xiaobin Tan, Xiongjian Wu","doi":"10.1002/mc.23897","DOIUrl":"10.1002/mc.23897","url":null,"abstract":"<p><p>Cuproptosis is a form of programmed cell death dependent on mitochondrial respiration and is crucial in cancer treatment. The study attempted to screen cuproptosis-associated genes in colorectal cancer (CRC) and reveal regulatory pathways. Weighted gene co-expression network analysis (WGCNA) was applied to screen the co-expression modules based on gene expression in CRC patients. The cuproptosis-associated genes were screened at the intersection of co-expression modules and cuproptosis gene data set. RNA sequencing was performed to assess the transcriptome changes, followed by functional enrichment analyses to reveal the potential pathways. Ferredoxin 1 (FDX1) was knocked down in in vivo and in vitro experiments to investigate the effects of FDX1 knockdown on CRC progression and cuproptosis. FDX1 was found as a cuproptosis-associated gene and was highly expressed in CRC tumor and CRC cells. Knockdown of FDX1 regulated cuproptosis in CRC cells, and inhibited CRC cell growth, migration and invasion. We screened 1956 upregulated DEGs and 2201 downregulated DEGs in si-FDX1 cells, which were mainly enriched in mitogen-activated protein kinase (MAPK) signaling pathway, tumor necrosis factor (TNF) signaling pathway and Hippo signaling pathway. Knockdown of FDX1 inhibited CRC progression by increasing the levels of dihydrolipoamide S-succinyltransferase (DLST), lipoic acid synthetase (LIAS) and phosphorylation Yes-associated protein (pYAP)/YAP, and downregulated transcriptional coactivator with a PDZ-binding domain (TAZ). The inhibitor of Hippo pathway GA-017 blocked this process. Knocking down FDX1 regulated cuproptosis and inhibited CRC progression by mediating the Hippo signaling pathway, which shed new insights into the development of biomarkers for CRC treatment.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"911-922"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483707","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":"VPS45 Contributes to the Progression of Hepatocellular Carcinoma by Triggering the Wnt/β-Catenin Signaling Pathway.","authors":"Renhou Zhi, Qi Li, Huiqin Zhang, Fan Fan","doi":"10.1002/mc.23884","DOIUrl":"10.1002/mc.23884","url":null,"abstract":"<p><p>Vacuolar protein sorting 45 (VPS45) has recently been implicated in the development of ovarian cancer and non-small cell lung cancer. However, its role in the onset and progression of hepatocellular carcinoma (HCC) remains unclear. This study aims to elucidate the function of VPS45 in HCC. Bioassays were conducted to assess the prognostic significance of VPS45 in HCC. Techniques such as western blotting and real-time quantitative polymerase chain reaction (qRT-PCR) were used to confirm the expression levels of VPS45 in HCC tissues and cell lines, as well as to evaluate the expression of downstream effectors in its potential tumorigenic pathways. The impact of VPS45 on HCC cell invasion, proliferation, and migration was assessed using the Cell Counting Kit-8 (CCK-8), wound healing, and transwell assays. Furthermore, the effect of VPS45 on HCC tumorigenesis in vivo was evaluated through subcutaneous tumor formation assays in BALB/c nude mice. VPS45 is markedly overexpressed in both HCC tissues and cell lines. Its expression escalates with advancing tumor grade and clinical stage, and high VPS45 levels are indicative of poor prognosis. In vitro experiments revealed that VPS45 overexpression significantly boosts HCC cell proliferation, migration, and invasion. Conversely, VPS45 knockdown hindered HCC progression in vivo. Investigation into pathway protein expression suggests that VPS45 facilitates HCC progression through its involvement in the Wnt/β-catenin signaling pathway. The overexpression of VPS45 contributes to the development of malignant phenotypes in HCC cells, resulting in a poor prognosis. Targeting VPS45 may offer a viable therapeutic strategy for managing HCC.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"744-755"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008768","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":"RNF7-Mediated ROS Targets Malignant Phenotype and Radiotherapy Sensitivity in Glioma With Different IDH1 Genotypes.","authors":"Yiran Tao, Zimin Shi, Xianyin Liang, Yuqian Zheng, Lirui Dai, Xiang Li, Zian Li, Wulong Liang, Gaojie Bai, Hao Li, Yuan Lyu, Junqi Li, Tao Zhang, Weihua Hu, Shaolong Zhou, Qiao Shan, Xudong Fu, Xinjun Wang","doi":"10.1002/mc.23876","DOIUrl":"10.1002/mc.23876","url":null,"abstract":"<p><p>RNF7 (Ring Finger Protein 7) is a key component of CRLs (Cullin-RING-type E3 ubiquitin ligases) and has been found to possess intrinsic anti-ROS capabilities. Aberrant expression of RNF7 has been observed in various tumor types and is known to significantly influence tumor initiation and progression. However, the specific role of RNF7 in glioblastoma remains unclear. IDH (isocitrate dehydrogenase) mutations, which induce metabolic reprogramming and result in notable heterogeneity among glioma with different IDH genotypes. Through analysis of public glioma databases, we identified a high expression of RNF7 in glioma and its correlation with patient prognosis. Moreover, we observed variations in RNF7 expression and its association with patient outcomes under different treatment modalities among different IDH genotypes. In this study, we demonstrated the critical role of RNF7 in the malignant phenotype of IDH1-mutant glioma and its contribution to radiation resistance. Subsequent functional enrichment analysis of RNF7 in glioma, coupled with validation through cellular experiments, confirmed its significant involvement in maintaining redox balance. Our findings suggest that RNF7 exerts a buffering effect against radiation-induced oxidative stress and counterbalances the redox stress induced by IDH1 mutation through its anti-ROS activity. Additionally, our follow-up investigations revealed that the upregulation of RNF7 after radiation exposure and in IDH1-mutant glioma cells is induced by ROS. Collectively, our study underscores the potential of RNF7 as a molecular biomarker in glioma. Elevated RNF7 expression often indicates a heightened metabolic resilience in glioma, leading to resistance against radiotherapy.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"652-667"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952059","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":"FKBP Prolyl Isomerase 11: A Novel Oncogene Interacting With SRSF1 in Esophageal Squamous Cell Carcinoma.","authors":"Zheng Ding, Zhichao Hou, Tangjuan Zhang, Peng Wang, Xue Pan, Xiangnan Li, Song Zhao","doi":"10.1002/mc.23877","DOIUrl":"10.1002/mc.23877","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is one of the main subtypes of esophageal carcinoma with high morbidity. This study aimed to explore the role of FKBP prolyl isomerase 11 (FKBP11) in ESCC and investigate the underlying mechanism. FKBP11 levels in ESCC tumor tissues and cell lines were measured. Cell function assays were conducted to evaluate the role of FKBP11 in ESCC cells. The xenograft mouse model was established to validate the effect of FKBP11 on ESCC tumorigenesis in vivo. The co-immunoprecipitation assay was performed to determine the FKBP11-interacting proteins. Obvious upregulations in FKBP11 expression were found in ESCC tumor tissues and cell lines. In vitro, FKBP11 knockdown weakened cell proliferation, migration, and invasion capacities and reinforced cell apoptosis in ESCC cells. In vivo, FKBP11 knockdown slowed ESCC tumorigenesis. The following mechanism investigation determined serine and arginine-rich splicing factor 1 (SRSF1) as the FKBP11-interacting protein in ESCC cells. FKBP11 directly bound to SRSF1 and FKBP11 knockdown decreased SRSF1 mRNA level. SRSF1 overexpression abrogated the inhibitory effect of FKBP11 knockdown on the proliferation and migration of ESCC cells. KBP11 functions as an oncogene in ESCC by targeting SRSF1.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"638-651"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952056","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":"LncRNA FGD5-AS1 Facilitates Hepatocellular Carcinoma Cell Stemness by Enhancing PKD1 mRNA Stability Through Binding With MSI2.","authors":"Chenkun He, Rongrong Liu, Tianli Zhou","doi":"10.1002/mc.23873","DOIUrl":"10.1002/mc.23873","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a major global health concern that accounts for more than 80% of all primary hepatic carcinomas. The long noncoding RNA FGD5 antisense RNA 1 (FGD5-AS1) has been linked to HCC cell stemness and proliferation. However, the exact function of FGD5-AS1 in HCC remains unclear. Cell viability and proliferation were examined using the CCK8 and colony formation assays, respectively. Cell stemness was examined using a sphere formation assay. To investigate the relation between Musashi 2 (MSI2) and FGD5-AS1 (or protein kinase D1 [PKD1]), RNA immunoprecipitation and RNA pull-down assays were used. Furthermore, a xenograft mouse model was established to evaluate the function of FGD5-AS1 in vivo. FGD5-AS1, MSI2, and PKD1 were upregulated in the HCC tissues. FGD5-AS1 knockdown significantly inhibited the viability, proliferation, and stemness of HCC cells and decreased the expression of MSI2, PKD1, octamer-binding transcription factor 4, SOX2, NANOG, and Prominin-1 in HCC cells. Mechanistically, FGD5-AS1 increased PKD1 mRNA stability by upregulating MSI2 expression. Both MSI2 and PKD1 ameliorated sh-FGD5-AS1's inhibition of HCC cell viability, proliferation, and stemness. Furthermore, FGD5-AS1 silencing inhibited HCC tumor growth and stemness in vivo. FGD5-AS1 promotes the stemness of HCC cells by activating the MSI2/PKD1 axis. Our study provides a new theoretical foundation for the development of novel HCC treatments.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"680-690"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971483","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}