Hypoxic microenvironment is clinically associated with metastasis and poor prognosis of numerous cancers. The mechanisms by which intratumoral hypoxia regulates metastasis are not fully understood. Our study identifies a downregulation of Lnc-CSMD1-7 in hepatocellular carcinoma (HCC) and correlated with poor prognosis of HCC patients. Lnc-CSMD1-7 negatively regulated HCC cell migration and invasion and suppressed lung metastasis . Mechanistically, Lnc-CSMD1-7 directly binds to RBFOX2, thereby affecting RBFOX2-regulated alternative splicing in epithelial and mesenchymal-specific events. More importantly, hypoxic microenvironment and m6A methylation mediate the downregulation of Lnc-CSMD1-7 expression. Specifically, hypoxia transcriptionally upregulates the expression of the m6A methyltransferase METTL16 via HIF-1α, and METTL16 directly binds to Lnc-CSMD1-7 and downregulates the RNA stability of Lnc-CSMD1-7 via m6A methylation, ultimately promoting HCC metastasis. Our findings highlight the regulatory function of the METTL16/Lnc-CSMD1-7/RBFOX2 axis in modulating hypoxia-induced HCC progression, which may provide potential prognostic and therapeutic targets for HCC treatment.
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| http://dx.doi.org/10.1016/j.isci.2023.108495 | DOI Listing |
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Background & Aims: This systematic literature review of qualitative findings aims to identify the perceived barriers and enablers for hepatocellular carcinoma (HCC) surveillance from patient and clinician perspectives.
Methods: A systematic search of databases using key term combinations with the following inclusion criteria: 1) qualitative and quantitative (survey) studies exploring barriers and enablers of HCC surveillance, and 2) qualitative and quantitative (survey) studies exploring barriers and enablers of enagagement in clinical care for patients with cirrhosis and/or viral hepatitis.
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