MicroRNA-377-3p targeting MMP-16 inhibits ovarian cancer cell growth, invasion, and interstitial transition.

Abstract

BackgroundTo evaluate role of microRNA (miRNA)-377-3p on the remission of ovarian cancer (OC) cell proliferation, invasion, and interstitial transition in vivo and vitro.MethodsSKOV3 cells were used as the object of in vitro research and four-week-old immunodeficient BABL/c female nude mice were used to form the xenograft model. Cell models were constructed by transfecting NC mimics, miR-377 mimic, plasmid cloning DNA (pcDNA), pc-matrix metalloproteinase (MMP)-16, or co-transfecting miR-377 mimic and pc-MMP-16. TargetScan software was used to predict the targeting relationship between miRNA-377-3p and MMP-16 in OC cells. The combination of miRNA-377-3p and MMP-16 was detected by dual luciferase report experiment. miRNA expression levels of miRNA-377-3p and MMP-16 in each transfection group cells were detected by reverse transcription-polymerase chain reaction (RT-PCR). The proliferation of SKOV3 cells were assessed by 5-ethynyl-2'-deoxyuridine (EdU) staining and microtubule formation, while the invasion ability of SKOV3 cells was detected by Transwell assay. Protein expression levels of MMP-16, survivin, Ki67, vascular endothelial growth factor (VEGF), E-cadherin, and N-cadherin were detected by Western blot (WB), and the positive cells of Ki67 and VEGF were detected by immunohistochemistry (IHC).ResultsMMP-16 overexpression markedly increased the EDU-positive cell percentage, upregulated survivin and Ki67 levels, increased the number of invasive cells per field, and enhanced VEGF and N-cadherin expression. Importantly, co-transfection of miRNA-377-3p and MMP-16 reversed these abnormal phenomena. Xenotransplantation mouse models were formed by injecting SKOV-3 cells subcutaneously. Tumor size, tumor volume, and tumor weight were all reduced in the miR-377-3p mimic–transfected group. The results of IHC indicated that Ki67 and VEGF expression were decreased in the miR-377-3p mimic–transfected group.ConclusionsThese findings indicate that miR-377-3p could be a promising therapeutic agent for OC cell growth, invasion, and interstitial transition with MMP-16 being its likely target.