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MiR-372-3p Predicts Response of TACE Patients Treated with Doxorubicin and Enhances Chemosensitivity in Hepatocellular Carcinoma.

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BACKGROUND Identification of factors to detect and improve chemotherapy-response in cancer is a main concern. microRNA-372-3p (miR-372-3p) has been demonstrated to play a crucial role in cellular proliferation, apoptosis and… Click to show full abstract

BACKGROUND Identification of factors to detect and improve chemotherapy-response in cancer is a main concern. microRNA-372-3p (miR-372-3p) has been demonstrated to play a crucial role in cellular proliferation, apoptosis and metastasis of various cancers including Hepatocellular Carcinoma (HCC). However, its contribution towards Doxorubicin (Dox) chemosensitivity in HCC has never been studied. OBJECTIVE This study aims to investigate the potential role of miR-372-3p in enhancing Dox effects on HCC cell line (HepG2). Their correlation has been additionally analyzed for HCC patients who received Transarterial Chemoembolization (TACE) with Dox treatment. METHODS Different cell processes were elucidated by cell viability, colony formation, apoptosis and wound healing assays after miR372-3p transfection in HepG2 cells Furthermore, miR-372-3p level has been estimated in blood of primary HCC patients treated with TACE/Dox by quantitative real-time PCR assay. Receiver Operating Curve (ROC) analysis for serum miR-372-3p was constructed for its prognostic significance. Finally, protein level of Mcl-1, the anti-apoptotic player, has been evaluated using western blot. RESULTS We found a significant higher level of miR-372-3p in blood of responder group of HCC patients received TACE with Dox than of non-responders. Ectopic expression of miR-372-3p reduced cell proliferation, migration and significantly induced apoptosis in HepG2 cells which was coupled with decreased of anti-apoptotic protein Mcl-1. CONCLUSION Our study demonstrated that miR-372-3p acts as tumor suppressor in HCC and can act as a predictor biomarker for drug response. Furthermore, the data referred for the first time its potential role in drug sensitivity that might be a therapeutic target for HCC.

Keywords: hepatocellular carcinoma; hcc; response; patients treated; mir 372

Journal Title: Anti-cancer agents in medicinal chemistry
Year Published: 2020

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