Inhibition of microRNA-383 has tumor suppressive effect in human epithelial ovarian cancer through the action on caspase-2 gene.

Abstract

MicroRNAs are important cancer regulators. In this work, we examined the expression pattern and mechanistic implications of microRNA-383 (miR-383) in human epithelial ovarian cancer (EOC). Gene expression level of miR-383 was compared by qRT-PCR between EOC cell lines and normal ovarian epithelial cell line, and between clinical EOC tumors and adjacent non-tumor ovarian epithelial tissues. Endogenous miR-383 was downregulated through lentiviral infection. Its effects on regulating EOC proliferation, cell cycle, invasion and in vivo explant development were assessed. Possible downstream target of miR-383 in EOC, human caspase-2 gene (CASP2), was evaluated by luciferase assay and qRT-PCR. CASP2 was then genetically knocked down by siRNA to assess its functional relationship with miR-383 in regulating EOC development both in vitro and in vivo. MiR-383 was overexpressed in both immortal EOC cell lines and human EOC tumors. In stably miR-383-downregulated EOC cell lines, cancer proliferation, cell cycle progression, invasion and in vivo explant development were significantly suppressed. CASP2 was confirmed to be downstream of miR-383 in EOC. SiRNA-mediated CASP2 downregulation had reverse relationship with miR-383 downregulation in regulating EOC development both in vitro and in vivo. Inhibition of miR-383 has profound tumor suppressing effect on EOC development. And the functional regulation of miR-383 in EOC is very likely inversely associated with CASP2 gene.