The miR-۳۸۳-LDHA axis regulates cell proliferation, invasion and glycolysis in hepatocellular cancer

Objective(s): To explore the correlation between expression patterns and functions of miR-۳۸۳ and LDHA in hepatocellular cancer (HCC). Materials and Methods: We detected the expression of miR-۳۸۳ and LDHA in ۳۰ HCC tissues and their matched adjacent normal tissues using qRT-PCR. Then we performed MTT assay, foci formation assay, transwell migration assay, glucose uptake assay and lactate production assay to explore the function of miR-۳۸۳ in cell proliferation, invasion and glycolysis in HCC cell lines. Luciferase reporter assay was used to explore whether LDHA was a target gene of miR-۳۸۳. Western blot and qRT-PCR were used to further confirm LDHA was targeted by miR-۳۸۳. Then the above functional experiments were repeated to see whether the function of LDHA could be inhibited by miR-۳۸۳. Results: The results of qRT-PCR showed that miR-۳۸۳ was down-regulated in HCC tissues compared with their matched adjacent normal tissues. Functional experiments showed that overexpression of miR-۳۸۳ significantly suppressed cell proliferation, invasion and glycolysis. Luciferase reporter assay showed LDHA was a target gene of miR-۳۸۳ and expression of LDHA was inversely correlated with that of miR-۳۸۳ in HCC. Besides, increased cell proliferation, invasion and glycolysis triggered by LDHA could be inhibited by overexpression of miR-۳۸۳ in HCC cell lines. Conclusion: Our study proved that miR-۳۸۳ is down-regulated in HCC and acts as a tumor suppressor through targeting LDHA. Targeting the miR-۳۸۳-LDHA axis might be a promising strategy in HCC treatment.

Keywords:

Hepatocellular cancer , LDHA , MiR-۳۸۳