In this study, we investigated the differential expression of microRNAs in an ovarian cancer cell line HO-8910PM with increased migration and invasiveness activities. miR-1 was found to be one of the microRNA species most significantly downregulated in HO-8910PM compared with the control cell line HO-8910. We demonstrated that ovarian cancer tissues expressed decreased levels of miR-1 compared to non-neoplastic tissues. In vitro experiments showed that overexpression of miR-1 in HO-8910PM led to an inhibition of cell proliferation, blocking of cell cycle progression by G1 phase arrest, and decreased migration and invasiveness of HO-8910PM cells. Moreover, we confirmed that the expression of c-Met, a potential target of miR-1, was significantly inhibited following overexpression of miR-1 in HO-8910PM cells. Further analyses indicated that expression of factors including p-Akt, p-ERK1/2, CDK4, and p-Rb in HO-8910PM cells were affected by manipulation of c-Met expression. Infection of HO-8910PM cells with lentivirus vector expressing miR-1 led to a significant inhibition of tumor growth in the tumor subcutaneous nude mouse model. Taken together, these results indicated that miR-1 is downregulated in ovarian cancer tissues, and may play a tumor suppressive role by inhibiting c-Met expression and its effects on the regulation of cell proliferation, migration and invasion.
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http://dx.doi.org/10.1016/j.cca.2017.07.008 | DOI Listing |
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