MicroRNA-30a-3p inhibits malignant progression of hepatocellular carcinoma through regulating IGF1.

OBJECTIVE

The purpose of this study was to investigate the expression level of microRNA-30a-3p in hepatocellular carcinoma (HCC), and to further study its relationship with HCC clinical parameters and prognosis and the underlying mechanisms.

PATIENTS AND METHODS

Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine microRNA-30a-3p level in 44 tumor tissue specimens and paracancerous normal ones collected from HCC patients, and the interplay between microRNA-30a-3p expression and clinical indicators, as well as prognosis of HCC patients was analyzed. Meanwhile, qPCR was also used to further verify microRNA-30a-3p expression in HCC cell lines. In addition, microRNA-30a-3p overexpression and knockdown models were constructed in HCC cell lines, and the impacts of microRNA-30a-3p on HCC cell functions was evaluated by cell counting kit-8 (CCK-8), transwell and cell wound healing assays. Finally, the Luciferase reporting assay was conducted to uncover the underlying mechanism.

RESULTS

In this study, qRT-PCR results showed that the expression level of microRNA-30a-3p in tumor tissues of HCC patients was markedly lower than that in adjacent ones. Compared with patients with high expression of microRNA-30a-3p, the patients with low expression of microRNA-30a-3p had a higher incidence of lymphatic or distant metastasis and a lower overall survival rate. In the Bel-7402 cell line, the proliferation, invasion, and metastasis ability of HCC cells were decreased markedly after microRNA-30a-3p overexpression, while in Hep3B cell line, knockdown of microRNA-30a-3p enhanced the cell proliferation and invasion capacity. In addition, Luciferase reporting assay demonstrated that microRNA-30a-3p could specifically bind to IGF1. Furthermore, Western Blot results also verified a reduced expression of IGF1 after overexpression of microRNA-30a-3p, and an elevated one after knockdown of microRNA-30a-3p. Finally, cell recovery experiment verified that microRNA-30a-3p and IGF1 may regulate each other and thereby together inhibit the malignant progression of HCC.

CONCLUSIONS

MicroRNA-30a-3p expression is significantly decreased in HCC tumor tissue samples, which is associated with lymph node or distant metastasis rate, as well as the poor prognosis of HCC. In addition, this research suggests that microRNA-30a-3p may inhibit the malignant progression of HCC by regulating IGF1.