MiR-888 promotes cell migration and invasion of hepatocellular carcinoma by targeting SMAD4

Y.-B. Li, F.-N. Sun, X.-Y. Ma, H. Qu, Y. Yu

Department of Blood Transfusion, Yantai Yuhuangding Hospital, Yantai, China. xmvv31@163.com

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• Oncology

OBJECTIVE: Hepatocellular carcinoma (HCC), a type of primary liver cancer, is the second leading cause of cancer mortality worldwide. Increasing evidence suggests that dysfunction of microRNAs (miRNAs) plays an important role in human cancers. MicroRNA-888 (miR-888) has been reported to be upregulated in multiple cancers that have a high rate of metastasis. The purpose of this study was to explore the molecular mechanisms of miR-888 in HCC cell migration and invasion.

PATIENTS AND METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting were employed to measure the levels of miR-888 and SMAD4 in HCC tissues and cell lines. To analyse the tissues and cell lines’ migratory and invasive abilities, Transwell assays were performed. To confirm that miR-888 regulates SMAD4 expression in HCC, a dual-luciferase reporter assay was applied.

RESULTS: MiR-888 was upregulated, while SMAD4 was downregulated, in HCC tissues and cell lines, and miR-888 and SMAD4 mRNA levels had a negative correlation. MiR-888 promoted cell migration and invasion in vitro. SMAD4 was thus confirmed as a direct and functional target of miR-888, and it could partially reverse the function of miR-888.

CONCLUSIONS: MiR-888 promoted cell migratory and invasive abilities and suppressed the expression of SMAD4 in HCC. The newly identified miR-888/SMAD4 axis provides novel insight into the progression of HCC and offers a promising target for HCC therapy.

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