{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yonezawa S"],"funding":["The Tsuchiya Memorial Medical Foundation"],"pagination":["733"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12468151"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["47(9)"],"pubmed_abstract":["Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, with limited therapeutic options and frequent resistance to treatment. The integrator complex subunit 6 (INTS6), a regulator of RNA polymerase II transcription, has emerged as a potential tumor suppressor that modulates Wnt/β-catenin signaling and epithelial-mesenchymal transition (EMT). This study aimed to clarify the role of INTS6 in EMT regulation in HCC and to explore the therapeutic potential of small activating RNA (saRNA)-mediated INTS6 induction. The Cancer Genome Atlas (TCGA) dataset was analyzed to assess the clinical relevance of INTS6 in HCC. Functional studies were conducted using a hepatoma cell line to determine the effects of INTS6 modulation on tumor behavior. Data analysis demonstrated that low INTS6 expression was associated with shorter disease-free survival and poorer prognosis in patients receiving conservative treatment. Experimental suppression of INTS6 increased mesenchymal marker expression, whereas saRNA-mediated induction suppressed these markers. Restoring INTS6 expression reduced cell migration, invasion, and proliferation through G1 cell-cycle arrest and enhanced sensitivity to sorafenib. These findings identify INTS6 as a promising therapeutic target in HCC. saRNA-mediated induction of INTS6 may provide a novel strategy, alone or in combination therapy, to overcome drug resistance and improve clinical outcomes."],"journal":["Current issues in molecular biology"],"pubmed_title":["Integrator Complex Subunit 6 Regulates Biological Nature of Hepatocellular Carcinoma by Modulating Epithelial-Mesenchymal Transition."],"pmcid":["PMC12468151"],"funding_grant_id":["N/A"],"pubmed_authors":["Yonezawa S","Shiozaki M","Ito M","Kanno K","Sugiyama M"],"additional_accession":[]},"is_claimable":false,"name":"Integrator Complex Subunit 6 Regulates Biological Nature of Hepatocellular Carcinoma by Modulating Epithelial-Mesenchymal Transition.","description":"Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, with limited therapeutic options and frequent resistance to treatment. The integrator complex subunit 6 (INTS6), a regulator of RNA polymerase II transcription, has emerged as a potential tumor suppressor that modulates Wnt/β-catenin signaling and epithelial-mesenchymal transition (EMT). This study aimed to clarify the role of INTS6 in EMT regulation in HCC and to explore the therapeutic potential of small activating RNA (saRNA)-mediated INTS6 induction. The Cancer Genome Atlas (TCGA) dataset was analyzed to assess the clinical relevance of INTS6 in HCC. Functional studies were conducted using a hepatoma cell line to determine the effects of INTS6 modulation on tumor behavior. Data analysis demonstrated that low INTS6 expression was associated with shorter disease-free survival and poorer prognosis in patients receiving conservative treatment. Experimental suppression of INTS6 increased mesenchymal marker expression, whereas saRNA-mediated induction suppressed these markers. Restoring INTS6 expression reduced cell migration, invasion, and proliferation through G1 cell-cycle arrest and enhanced sensitivity to sorafenib. These findings identify INTS6 as a promising therapeutic target in HCC. saRNA-mediated induction of INTS6 may provide a novel strategy, alone or in combination therapy, to overcome drug resistance and improve clinical outcomes.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-05-02T03:19:58.963Z","creation":"2026-05-02T03:11:57.19Z"},"accession":"S-EPMC12468151","cross_references":{"pubmed":["41020855"],"doi":["10.3390/cimb47090733"]}}