| Hepatocellular Carcinoma(HCC) is one of the most malignant tumor with high death rate all over the world. The molecular mechanism of the formation of primary liver cancer is still unclear. Current researches show that abnormal expression of microRNA plays an important role in the formation of HCC. In this study, we analyzed the expression of miR-370in some HCC and their cancer adjacent tissues, the influence of miR-370for proliferation and tumor formation of HCC cells, and the effect of miR-370on LIN28expression. The results suggested that miR-370could be a novel therapeutic target of HCC.First, we compared the expression of miR-370in liver cancer tissues and their adjacent tissues, and found that miR-370is downregulated in most liver cancer tissues, as well as in different cultured liver tumor cells. MiR-370overexpression inhibited the proliferation of MHCC-H and PLC cells. Conversely, proliferation of these cells could be increased by restraining miR-370effect. In addition, overexpression of miR-370suppressed colony formation of MHCC-H, PLC, HepG2and Huh7cells. Soft-Agar Colony Assay demonstrated that overexpression of mi-370inhibited the anchorage-independent growth of MHCC-H cell, confirmed that miR-370could restrain both proliferation and tumor formation ability of HCC cells.We further analyzed the target genes of miR-370. By using the prediction software, we found that the stem cell related RNA-binding protein LIN28is a potential target gene of miR-370. Real-time fluorescence quantitative PCR displayed that overexpression of miR-370decreased the expression of LIN28. Dual-Luciferase Reporter experiment with construct containing the fragment of LIN283’UTR comfirmed that LIN28is a target gene of miR-370. In addition, the expression of stem cell related markers, such as Sox2, Nanog, Oct3/4,were suppressed by miR-370overexpression in Hep3B cell. Therefore, miR-370might suppress HCC tumor formation by targeting LIN28and increasing the differentiation of cancer stem cells. |
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