Background: Doxorubicin (DOX) is one of the most common drugs used in cancer therapy, including
Hepatocellular Carcinoma (HCC). Drug resistance is one of chemotherapy’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 microRNA-520c-3p (miR-520c-3p) in the enhancement of the anti-tumor
effect of DOX against HepG2 cells.
Methods: 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. The 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 the western blot technique.
Results: The present data indicated 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. The
suppressive effect of miR-520c-3p involved altering the expression levels of some key regulators of cell
cycle, proliferation, migration and apoptosis, including LEF1, CDK2, CDH1, VIM, Mcl-1 and p53. Interestingly,
Mcl-1 was found to be one of the potential targets of miR-520c-3p, and its protein expression level was
down-regulated upon miR-520c-3p overexpression.
Conclusion: Our data referred to the tumor suppressor function of miR-520c-3p that could modulate the
chemosensitivity of HepG2 cells towards DOX treatment, providing a promising therapeutic strategy in HCC.