Conclusions
Our data suggest a potential role for miR-233-3p as a prognostic as well as a therapeutic target for HCC.
Methods
Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the expression level of 14 MDR-related miRNAs in doxorubicin-resistant HepG2 cells (HepG2/Dox) developed by single-dose of doxorubicin mimicking the situation of liver cells surviving TACE. The sera level of miR-223-3p, which was the most significantly downregulated in the HepG2 cells, was determined in 60 primary HCC patients undergoing TACE. Restoring miR-223-3p in HepG2/Dox cell line was achieved by its mimic transfection. Cell sensitivity was measured by SRB assay. Cell apoptosis and doxorubicin uptake were assessed by flow cytometry. The expression of miR-223-3p target protein, P-glycoprotein, was evaluated using qRT-PCR and western blotting.
Results
We detected a significant downregulation of circulating miR-223-3p in patients non-responders to TACE treatment compared with responders. The expression of miR-223-3p was markedly decreased in resistant HepG2/Dox cells compared to the parental control. In addition, the expression of miR-223-3p was found to be inversely correlated with P-glycoprotein expression thus confirming the role of miR-223-3p in MDR. Furthermore, overexpression of miR-223-3p suppressed P-glycoprotein which promoted cellular uptake of doxorubicin and increased apoptosis. Conclusions: Our data suggest a potential role for miR-233-3p as a prognostic as well as a therapeutic target for HCC.