MiRNA-15a-3p inhibits the metastasis of hepatocellular carcinoma by interacting with HMOX1.

OBJECTIVE

To uncover the relationship between microRNA-15a-3p (miRNA-15a-3p) level and clinical features of hepatocellular carcinoma (HCC), and to explore the influence of miRNA-15a-3p on metastasis of HCC cells.

PATIENTS AND METHODS

HCC and paracancerous tissues were surgically resected from 44 HCC patients. Their clinical data and follow-up files were recorded. Differential expressions of miRNA-15a-3p in HCC samples were determined. The relationship between miRNA-15a-3p level and clinical features of HCC patients was analyzed. Changes in proliferative, migratory and invasive potentials in Huh7 and HepG2 cells overexpressing miRNA-15a-3p were examined. The downstream gene of miRNA-15a-3p and its involvement in HCC development were finally explored.

RESULTS

MiRNA-15a-3p was downregulated in HCC tissues. High metastasis rate and poor prognosis were observed in HCC patients expressing a low level of miRNA-15a-3p. Overexpression of miRNA-15a-3p attenuated proliferative, migratory and invasive potentials in HCC. Protein levels of HMOX1, CD31, c-Myc, MMP-2 and MMP-9 were downregulated in HCC cells after overexpression of miRNA-15a-3p. HMOX1 was the downstream gene of miRNA-15a-3p, which was upregulated in HCC samples. Highly expressed HMOX1 was unfavorable to the prognosis in HCC. Overexpression of HMOX1 abolished the regulatory effects of miRNA-15a-3p on HCC cell phenotypes.

CONCLUSIONS

MiRNA-15a-3p is closely linked to lymphatic metastasis, distant metastasis and poor prognosis in HCC. It inhibits the malignant development of HCC by interacting with HMOX1.