HULC functions as an oncogene in ovarian carcinoma cells by negatively modulating miR-125a-3p
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ORIGINAL ARTICLE
HULC functions as an oncogene in ovarian carcinoma cells by negatively modulating miR-125a-3p Ping Chu 1 & Lina Xu 1 & Haiying Su 1 Received: 21 November 2018 / Accepted: 19 February 2019 # University of Navarra 2019
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. Keywords Ovarian carcinoma . HULC . miR-125a-3p . PI3K/AKT/mTOR signaling pathway
Introduction Ovarian cancer has high mortality. It has been reported that there were approximately 184,799 ovarian cancer deaths and the age-standardized mortality of ovarian cancer was 3.9 per 100,000 all over the world. Meanwhile, the proportion of Highlights 1. HULC negatively mediates miR-125a-3p expression in ovarian carcinoma cells SKOV3. 2. HULC overexpression promotes ovarian carcinoma development by downregulating miR-125a-3p in SKOV3 cells. 3. Upregulated miR-125a-3p blocks PI3K/AKT/mTOR pathway activated by HULC overexpression. Ping Chu and Lina Xu contributed equally to this work. * Haiying Su [email protected] 1
Department of Gynecology, Jining No.1 People’s Hospital, No.6 Jiankang Road, Jining 272011, China
deaths died from ovarian cancer in all cancers deaths was 2.08%, ranking 15th in 2018 according to the report from international agency for research on cancer (IARC) [1]. The difficulties in diagnosing early stage are the primary leading to its high mortality [19]
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