Thesis (Ph.D.) - Cairo University - Faculty of Science - Department of Biochemistry

Identification of factors to detect and improve chemotherapy{u2010}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. 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. Different cell processes were elucidated by cell viability, colony formation, apoptosis, and wound healing assays after miR-372-3p 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 antiapoptotic player, has been evaluated using western blot. We found a significant higher level of miR-372-3p in blood of responder group of HCC patients received TACE with Dox than of nonresponders. Ectopic expression of miR-372-3p reduced cell proliferation, migration and significantly induced apoptosis in HepG2 cells which was coupled with decreased of antiapoptotic protein Mcl-1. 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

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