Background:
Doxorubicin (DOX) is 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 miR-520c-3p in enhancement of 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. Expression level for LEF1, CDK2, CDH1,
VIM, Mcl-1 and TP53 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 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 TP53. 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 chemosensitivity of HepG2 cells toward DOX treatment, providing a promising
therapeutic strategy in HCC.
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