MicroRNA-122 restoration modulates alpha-fetoprotein expression in hepatocellular carcinoma treated with doxorubicin

Abstract

Higher levels of morbidity and mortality are due to malignant tumors and Hepatocellular carcinoma (HCC) is considered of a great percentage. The liver-specific microRNA-122 (mir-122) is frequently down-regulated in HCC and is a promising biomarker for the early HCC diagnosis. Restoration of mir-122 renders HCC cells to be sensitive to doxorubicin. The present study aims to investigate the effect of treatment of HCC cells with doxorubicin and/or mir-122 mimics on AFP expression levels. Using HepG2 cells with different treatments, AFP mRNAs and proteins were isolated and detected by real-time PCR and ELISA, respectively. Our data showed that there was a dynamic change in mir-122 expression as compared to inhibitor negative control. Also, there were no significant differences in AFP expression levels in cells treated with chronic doxorubicin dose then transfected with mir-122 mimics. However, our findings demonstrated statistical significant increase in both molecular and protein expression levels of AFP in cells treated with acute high doxorubicin dose and mir-122 mimics. This could be associated with increasing doxorubicin sensitivity by mir-122 restoration in HepG2 cells. This distinct finding could be attributed to a negative feedback increase in AFP levels to counteract the apoptosis/reactive oxygen species triggered by miR- 122 restoration in doxorubicin-treated HepG2 cells.