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MiR-451a suppresses cell proliferation, metastasis and EMT via targeting YWHAZ in hepatocellular carcinoma.

OBJECTIVE
MicroRNAs (miRNAs) have been identified to participate in the progression of hepatocellular carcinoma (HCC). However, the function of miR-451a in HCC remains unknown. The aim of this study was to determine the function of miR-451a by construction of several experiments in HCC tissues and cells.


PATIENTS AND METHODS
The expression level of miR-451a in 69 paired of HCC and adjacent normal tissue samples was detected using quantitative Real-time polymerase chain reaction (qRT-PCR). MiR-451a expression in HCC derived cell lines was detected as well. By transfecting with miR-451a mimics or inhibitor, the expression level of miR-451a in HepG2 or Huh-7 cells was up- or down-regulated. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and colony formation analysis were employed to evaluate the changes of cell proliferation. Cell migration and invasion abilities were measured via transwell assay. Meanwhile, the underlying mechanism of miR-451a in HCC was demonstrated and verified by dual-luciferase assay and Western blotting, respectively. Rescue experiments were used to identify the downstream molecule of miR-451a in HCC.


RESULTS
MiR-451a expression in HCC tissue samples was significantly lower than that of adjacent normal samples. Meanwhile, the level of miR-451a in HCC cell lines was significantly down-regulated when compared with normal human hepatic cell line LO2. MTT assay and colony formation analysis showed that over-expressed miR-451a remarkably inhibited proliferation of HepG2 cells, whereas down-regulated miR-451a promoted growth of Huh-7 cells. Transwell results indicated that up-regulation of miR-451a significantly decreased HCC cell invasion and migration, while down-regulation remarkably increased cell metastasis. Furthermore, YWHAZ was identified as a direct target for miR-451a in HCC cells.


CONCLUSIONS
The expression level of miR-451a was decreased in HCC tissues and cell lines. Moreover, miR-451a inhibited the proliferation, invasion and migration of HCC cells via targeting YWHAZ. Our findings indicated that miR-451a could serve as a novel target for HCC diagnosis and biological therapy.