PMID- 30470261 OWN - NLM STAT- MEDLINE DCOM- 20190423 LR - 20191210 IS - 1476-4598 (Electronic) IS - 1476-4598 (Linking) VI - 17 IP - 1 DP - 2018 Nov 23 TI - CircSLC3A2 functions as an oncogenic factor in hepatocellular carcinoma by sponging miR-490-3p and regulating PPM1F expression. PG - 165 LID - 10.1186/s12943-018-0909-7 [doi] LID - 165 AB - BACKGROUND: Non-coding RNAs (ncRNAs) have been reported to participate in tumor progression by regulating gene expression. Previous studies showed that protein phosphatase Mg2(+)/Mn2(+) dependent 1F (PPM1F) acts a dual role in cancer growth and metastasis. But, the underlying mechanisms by which ncRNAs regulate PPM1F expression in hepatocellular carcinoma (HCC) are poorly understood. METHODS: The association between PPM1F or miR-490-3p expression and clinicopathological features and prognosis in patients with HCC was analyzed by TCGA RNA-sequencing data. CircSLC3A2 was identified to bind with miR-490-3p by bioinformatic analysis, and the binding sites between miR-490-3p and PPM1F or circSLC3A2 were confirmed by dual luciferase report and RNA immunoprecipitation (RIP) assays. The localization and clinical significance of miR-490-3p and circSLC3A2 in patients with HCC were investigated by fluorescence in situ hybridization (FISH). MTT, Agar, and Transwell assays were conducted to evaluate the effects of miR-490-3p or circSLC3A2 on cell proliferation and invasive potential. RESULTS: The expression of PPM1F or miR-490-3p was associated with poor survival and tumor recurrence, and acted as an independent prognostic factor in patients with HCC. Re-expression of miR-490-3p inhibited HCC cell proliferation and invasion by targeting PPM1F, but its inhibitor reversed these effects. Moreover, circSLC3A2, predominantly localized in the cytoplasm, exhibited an oncogenic role by sponging miR-490-3p and regulating PPM1F expression, and harbored a positive correlation with poor survival in patients with HCC. CONCLUSION: CircSLC3A2 acts as an oncogenic factor in HCC by sponging miR-490-3p and regulating PPM1F expression. FAU - Wang, Hongjian AU - Wang H AD - The Fifth Department of Digestion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China. FAU - Chen, Wei AU - Chen W AD - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China. FAU - Jin, Ming AU - Jin M AD - Department of Clinical Medicine, Ningbo University School of Medicine, Ningbo, 315211, Zhejiang Province, China. FAU - Hou, Lidan AU - Hou L AD - Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Chen, Xiaoyu AU - Chen X AD - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China. FAU - Zhang, Rui AU - Zhang R AD - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China. FAU - Zhang, Jing AU - Zhang J AUID- ORCID: 0000-0003-4733-9442 AD - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China. jing5522724@vip.163.com. FAU - Zhu, Jinshui AU - Zhu J AD - Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181123 PL - England TA - Mol Cancer JT - Molecular cancer JID - 101147698 RN - 0 (3' Untranslated Regions) RN - 0 (Fusion Regulatory Protein 1, Heavy Chain) RN - 0 (MIRN490 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - 0 (SLC3A2 protein, human) RN - 63231-63-0 (RNA) RN - EC 3.1.3.16 (PPM1F protein, human) RN - EC 3.1.3.16 (Phosphoprotein Phosphatases) SB - IM MH - 3' Untranslated Regions MH - Carcinoma, Hepatocellular/*genetics/mortality/pathology MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - Cell Transformation, Neoplastic MH - Fusion Regulatory Protein 1, Heavy Chain/*genetics MH - *Gene Expression Regulation, Neoplastic MH - Genes, Reporter MH - Humans MH - Liver Neoplasms/*genetics/mortality/pathology MH - MicroRNAs/*genetics MH - Models, Biological MH - Oncogenes MH - Phosphoprotein Phosphatases/*genetics MH - Prognosis MH - *RNA MH - RNA Interference MH - RNA, Circular PMC - PMC6260990 OTO - NOTNLM OT - CircSLC3A2 OT - Hepatocellular carcinoma OT - Invasion OT - MiR-490-3p OT - PPM1F OT - Proliferation COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The present study was approved by the Hospital's Protection of Human Subjects Committee. CONSENT FOR PUBLICATION: Consent for publication has been obtained from the patients. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/11/25 06:00 MHDA- 2019/04/24 06:00 PMCR- 2018/11/23 CRDT- 2018/11/25 06:00 PHST- 2018/08/03 00:00 [received] PHST- 2018/11/01 00:00 [accepted] PHST- 2018/11/25 06:00 [entrez] PHST- 2018/11/25 06:00 [pubmed] PHST- 2019/04/24 06:00 [medline] PHST- 2018/11/23 00:00 [pmc-release] AID - 10.1186/s12943-018-0909-7 [pii] AID - 909 [pii] AID - 10.1186/s12943-018-0909-7 [doi] PST - epublish SO - Mol Cancer. 2018 Nov 23;17(1):165. doi: 10.1186/s12943-018-0909-7.