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

Background: Doxorubicin (Dox) is one of the most common drugs used in cancer therapy, including hepatocellular carcinoma (HCC). Drug resistance, is one of chemotherapy{u2019}s significant problems. Emerging studies have shown that microRNAs (miRNAs) could participate in regulating this mechanism. Nevertheless, the impact of miRNAs on HCC chemoresistance is still enigmatic. Objective: Investigating the role of a candidate miRNA in enhancement of anti-tumor effects of Dox against HepG2 cells. Expression profile for liver related miRNAs (384 miRNAs) has been analyzed on HepG2 cells treated with Dox using qRT-PCR. miR- 520c-3p, the most deregulated miRNA, was selected for combination treatment with Dox. Methods: Expression level for LEF1, CDK2, CDH1, VIM, Mcl-1 and p53 was evaluated in miR-520c-3p transfected cells. Cell viability, colony formation, wound healing as well as apoptosis assays have been demonstrated. Furthermore, Mcl-1 protein level was measured using a western blot technique. Results: The present data indicates that miR-520c-3p overexpression could render HepG2 cells chemo-sensitive to Dox through enhancing its suppressive effects on proliferation, migration, and induction of apoptosis

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