Abstract:
Objective To investigated the effects of microRNA(miR)-370-3p on growth and metabolism of ovarian cancer (OC) SKOV3 cells and aimed to elucidate the underlying mechanisms.
Methods Expression of miR-370-3p and histone deacetylase 4 (HDAC4) mRNA in OC tissues and cells was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The relationship between miR-370-3p and HDAC4 was assessed using dual luciferase assay. Relative expression of Ki-67, proliferating cell nuclear antigen (PCNA), cleaved caspase-3, Bax, and HDAC4 was analyzed using Western blot. Further, cell proliferation was detected using Cell Counting Kit-8 assay, and apoptosis rates were assessed using flow cytometry. Cellular glycolysis capacity and mitochondrial functions were analyzed using a Seahorse XF24 analyzer. Furthermore, xenograft models were established by transplanting SKOV3 cells into, in which tumor volume and weight were recorded, and expression of Ki-67 and caspase-3 was analyzed using immunohistochemistry.
Results MiR-370-3p and HDAC4 showed low and high expression, respectively, in the OC tissues and cells. Further, miR-370-3p overexpression was found to downregulate HDAC4 expression. It also reduced cell proliferation, glycolysis rate, glycolysis capacity, and PCNA and Ki-67 protein expression, but increased apoptosis, basal and maximum respiration rates, and cleaved caspase-3 and Bax protein expression; these results were statistically significant at P < 0.01. In vivo, miR-370-3p overexpression reduced the size and weight of SKOV3 cell-induced tumors, proportion of caspase-3-positive cells, glycolysis rate, and glycolysis capacity, but increased the proportion of Ki-67-positive cells and basal and maximum respiration rates; these results were also statistically significant at P < 0.01.
Conclusions MiR-370-3p overexpression can inhibit OC cell growth by downregulating HDAC4 and alter OC cell metabolism.