OIP5-AS1 contributes to tumorigenesis in hepatocellular carcinoma by miR-300/YY1-activated WNT pathway
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Cancer Cell International Open Access
PRIMARY RESEARCH
OIP5‑AS1 contributes to tumorigenesis in hepatocellular carcinoma by miR‑300/ YY1‑activated WNT pathway Yu Wang1,2,3, Lei Dou4, Yun Qin5, Huiyuan Yang1* and Peng Yan6*
Abstract Background: It has reported that long non-coding RNAs (lncRNAs) exerted regulatory functions by targeting specific genes through a competing endogenous RNA (ceRNA) pathway. LncRNA OIP5-AS1 has been identified as a tumorenhancer in several tumor types. Nonetheless, its molecular mechanism in HCC remains to be masked. Aim of the study: This study was aimed at exploring whether and how OIP5-AS1 exert functions in HCC. Methods: qRT-PCR and western blot were employed for detecting gene expression. CCK-8, colony formation and EdU assays were implemented to evaluate the proliferative ability of HCC cells. Caspase-3 activity and flow cytometry analyses were implemented to determine cell apoptosis and cell cycle distribution. RNA pull down, ChIP, RIP and luciferase reporter assays explored the interplays between molecules. Results: YY1 was upregulated in HCC cells, and silenced YY1 restrained HCC cell proliferation in vitro and hampered tumor growth in vivo. Later, we discovered that miR-300 could regulate WNT pathway via targeting YY1. Furthermore, OIP5-AS1 was identified as the sponge of miR-300 and promoted cell growth in HCC. Importantly, YY1 transcriptionally activate OIP5-AS1 in turn. Rescue experiments indicated that miR-300 inhibition or YY1 overexpression abrogated the inhibitive effect of OIP5-AS1 silencing on the malignant growth of HCC cells. Conclusions: OIP5-AS1/miR-300/YY1 feedback loop facilitates cell growth in HCC by activating WNT pathway. Keywords: OIP5-AS1, miR-300, YY1, WNT pathway, Hepatocellular carcinoma Background As the most frequent subtype of liver cancer [1], hepatocellular carcinoma (HCC) ranks second among the cancers contributing to death globally [2]. Recent years, the pre-clinical treatment strategies have been gradually reported [3, 4]. Despite great improvement in interventional therapy has been made for HCC, the clinical effect remains disappointed due to the difficulty in early *Correspondence: [email protected]; [email protected] 1 Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China 6 Department of Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China Full list of author information is available at the end of the article
diagnosis of HCC patients [5]. Thus, the imperious demand for novel biomarkers in HCC needs to be met. Long non-coding RNAs (lncRNAs), greater than 200 nucleotides in length, have limitations in protein-coding capacity [6]. Current reports have disclosed the critical implication of lncRNAs in physiological and pathological, including organismal viability, immunity, tumorigenesis, organ development and tumor progression [7–9]. In addition, the roles that lncRNAs served in
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