PMID- 30068940 OWN - NLM STAT- MEDLINE DCOM- 20190228 LR - 20230309 IS - 1476-5594 (Electronic) IS - 0950-9232 (Linking) VI - 37 IP - 50 DP - 2018 Dec TI - PTBP3 splicing factor promotes hepatocellular carcinoma by destroying the splicing balance of NEAT1 and pre-miR-612. PG - 6399-6413 LID - 10.1038/s41388-018-0416-8 [doi] AB - Nuclear-enriched RNA-binding proteins (RBPs) are mainly involved in transcriptional regulation, which is a critical checkpoint to tune gene diversity and expression levels. We analyzed nuclear RBPs in human HCC tissues and matched normal control tissues. Based on the gene expression levels, PTBP3 was identified as top-ranked in the nuclei of HCC cells. HCC cell lines then were transfected with siRNAs or lentiviral vectors. PTBP3 promoted HCC cell proliferation and metastasis both in vitro and in vivo. RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and qRT-PCR assays verified that PTBP3 protein recruited abundant lnc-NEAT1 splicing variants (NEAT1_1 and NEAT1_2) and pre-miR-612 (precursor of miR-612) in the nucleus. NEAT1_1, NEAT1_2 and miR-612 expression levels were determined by PTBP3. Correlational analyses revealed that PTBP3 was positively correlated with NEAT1, but it was inversely correlated with miR-612 in HCC. The P53/CCND1 and AKT2/EMT pathways were determined by NEAT1 and miR-612 respectively in HCC. The PTBP3(high) and NEAT1(high)/miR-612(low) patients had a shorter overall survival. Therefore, nuclear-enriched RBP, PTBP3, promotes HCC cell malignant growth and metastasis by regulating the balance of splicing variants (NEAT1_1, NEAT1_2 and miR-612) in HCC. FAU - Yang, Xisheng AU - Yang X AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. FAU - Qu, Shibin AU - Qu S AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. AD - Section of General Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA. FAU - Wang, Lin AU - Wang L AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. FAU - Zhang, Hongtao AU - Zhang H AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. FAU - Yang, Zhaoxu AU - Yang Z AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. FAU - Wang, Jianlin AU - Wang J AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. FAU - Dai, Bin AU - Dai B AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. FAU - Tao, Kaishan AU - Tao K AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. FAU - Shang, Runze AU - Shang R AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. FAU - Liu, Zhengcai AU - Liu Z AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. FAU - Li, Xiao AU - Li X AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. FAU - Zhang, Zhuochao AU - Zhang Z AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. FAU - Xia, Congcong AU - Xia C AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. FAU - Ma, Ben AU - Ma B AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. FAU - Liu, Wei AU - Liu W AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. FAU - Li, Haimin AU - Li H AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. lihaim@fmmu.edu.cn. FAU - Dou, Kefeng AU - Dou K AD - Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China. doukef@fmmu.edu.cn. LA - eng GR - 81672339/National Natural Science Foundation of China (National Science Foundation of China)/International PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Retracted Publication DEP - 20180801 PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (MALAT1 long non-coding RNA, human) RN - 0 (MIRN612 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (NEAT1 long non-coding RNA, human) RN - 0 (PTBP3 protein, human) RN - 0 (RNA, Long Noncoding) RN - 139076-35-0 (Polypyrimidine Tract-Binding Protein) SB - IM RIN - Oncogene. 2023 Apr;42(15):1263. PMID: 36890279 MH - Animals MH - Carcinoma, Hepatocellular/metabolism/*pathology MH - Female MH - Gene Expression Regulation, Neoplastic/*genetics MH - Humans MH - Liver Neoplasms/metabolism/*pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*genetics/metabolism MH - Polypyrimidine Tract-Binding Protein/*metabolism MH - RNA, Long Noncoding/*genetics/metabolism EDAT- 2018/08/03 06:00 MHDA- 2019/03/01 06:00 CRDT- 2018/08/03 06:00 PHST- 2017/12/31 00:00 [received] PHST- 2018/06/29 00:00 [accepted] PHST- 2018/05/31 00:00 [revised] PHST- 2018/08/03 06:00 [pubmed] PHST- 2019/03/01 06:00 [medline] PHST- 2018/08/03 06:00 [entrez] AID - 10.1038/s41388-018-0416-8 [pii] AID - 10.1038/s41388-018-0416-8 [doi] PST - ppublish SO - Oncogene. 2018 Dec;37(50):6399-6413. doi: 10.1038/s41388-018-0416-8. Epub 2018 Aug 1.