HOTAIRM1 suppresses cell proliferation and invasion in ovarian cancer through facilitating ARHGAP24 expression by sponging miR-106a-5p

Abstract

AimsOvarian cancer (OC) is the most lethal gynecologic malignant tumors all over the world. HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) has been reported as an important regulator in multiple tumors. However, the functions of HOTAIRM1 in OC and its possible molecular mechanisms remain unclear. Main methodsqRT-PCR analysis was performed to detect the expression levels of HOTAIRM1, miR-106a-5p and ARHGAP24 mRNA in OC tissues and cells. The functional effects of HOTAIRM1, miR-106a-5p and ARHGAP24 on OC cells were determined by MTT, colony formation, flow cytometry and Transwell assays. Luciferase reporter, RIP and RNA pull-down assays were used to examine the interaction between miR-106a-5p and HOTAIRM1 or ARHGAP24. Tumor xenografts were constructed in nude mice to confirm the roles of HOTAIRM1 in OC in vivo. Key findingsHOTAIRM1 expression was lowered in OC tumor tissues and cells. Decreased HOTAIRM1 expression was associated with advanced FIGO stages and lymphatic metastasis. Up-regulation of HOTAIRM1 suppressed OC cell proliferation and invasion, and promoted apoptosis. Also, HOTAIRM1 slowed OC tumor growth in vivo. Moreover, HOTAIRM1 could serve as a competing endogenous RNA (ceRNA) of miR-106a-5p to derepress ARHGAP24 expression. HOTAIRM1-mediated inhibitory effect on OC progression was partly reversed following the restoration of miR-106a-5p expression. Furthermore, ARHGAP24 overexpression repressed OC progression in vitro. SignificanceIn conclusion, our study showed that HOTAIRM1 suppressed OC progression through derepression of ARHGAP24 by sponging miR-106a-5p. This finding provides novel insights into the mechanisms of HOTAIRM1 in OC and highlights a potential therapeutic strategy for the treatment of OC.