Hypoxia-induced miR-3677-3p promotes the proliferation, migration and invasion of hepatocellular carcinoma cells by suppressing SIRT5

Hepatocellular carcinoma (HCC), with life-threatening malignant behaviours, often develops distant metastases and is the fourth most common primary cancer in the world, having taken millions of lives in Asian countries such as China. The novel miR-3677-3p is involved in a high-expression-related poor prognosis in HCC tissues and cell lines, indicating oncogenesis functions in vitro and in vivo. Initially, we confirmed the inhibition of proliferation, migration and invasion in miR-3677-3p knock-down MHCC-97H and SMMC-7721 cell lines, which are well known for their high degree of invasiveness. Then, we reversed the functional experiments in the low-miR-3677-3p-expression Hep3B cell line via overexpressing miR-3677-3p. In nude mice xenograft and lung metastasis assays, we found suppressor behaviours, smaller nodules and low density of organ spread, after injection of cells transfected with shRNA-miR-3677-3p. A combination of databases (Starbase, TargetScan and MiRgator) illustrated miR-3677-3p targets, and it was shown to suppress the expression of SIRT5 in a dual-luciferase reporter system. To clarify the conclusions of previous ambiguous research, we up-regulated SIRT5 in Hep3B cells, and rescue tests were established for confirmation that miR-3677-3p suppresses SIRT5 to enhance the migration and invasion of HCC. Interestingly, we discovered hypoxia-induced miR-3677-3p up-regulation benefited HCC malignancy and invasiveness. In conclusion, the overexpression of miR-3677-3p mediated SIRT5 inhibition, which could increase proliferation, migration and invasion of HCC in hypoxic microenvironments.