HULC functions as an oncogene in ovarian carcinoma cells by negatively modulating miR-125a-3p.

Abstract

The aberrant expression of highly upregulated in liver cancer (HULC) has been reported to participate in ovarian cancer development. A recent research has revealed that HULC-modulated microRNAs (miRNAs) in tumorigenesis. To confirm the functions of HULC on tumorigenesis of ovarian, we explored the effects of HULC expression on ovarian cancer cell development, as well as the underlying mechanism. We transfected SKOV3 cells with pEX-HULC, sh-HULC, and miR-125a-3p mimic as well as their corresponding negative controls (pEX-3, sh-NC, and NC) to alter the expression of HULC and miR-125a-3p, which were analyzed by quantitative reverse transcription PCR (qRT-PCR). Expression of proteins associated with cell cycle, apoptosis, and signaling pathways was determined by Western blot assay. The proliferation, apoptosis, migration, and invasion were explored by bromodeoxyuridine (BrdU) incorporation assay, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) method, and transwell migration and invasion assays, respectively. HULC overexpression promoted proliferation, migration, and invasion, while inhibited apoptosis of SKOV3 cells. In addition, HULC negatively regulated the expression of miR-125a-3p. Besides, miR-125a-3p mimic reversed the effects of HULC on proliferation, migration, and invasion as well as apoptosis of SKOV3 cells. Moreover, we found that HULC enhanced phosphorylated expression of regulatory factors in phosphatidylinositol 3 kinase/protein kinase B/mammalian targets of rapamycin (PI3K/AKT/mTOR) signaling pathway by downregulating expression of miR-125a-3p. Overexpression of HULC promoted ovarian carcinoma development by activating PI3K/AKT/mTOR signaling pathway via downregulating miR-125a-3p.