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RETRACTED ARTICLE: PTBP3 splicing factor promotes hepatocellular carcinoma by destroying the splicing balance of NEAT1 and pre-miR-612

Oncogene volume 37, pages 6399–6413 (2018)Cite this article

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This article was retracted on 08 March 2023

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Abstract

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 PTBP3high and NEAT1high/miR-612low 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.

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Acknowledgements

The authors thank Kun Liu and Huimin Wang (Department of Hepatobiliary Surgery of Xijing Hospital) for collecting the tissue samples and the follow-up information.

Authors contributions

XY, KD and HL designed the experiments and wrote the paper; SQ, LW, HZ and ZY performed bioinformatics and statistical analyses; JW, KT, ZL, ZZ and BD performed the histopathologic analyses; CX, BM, RS, XL and WL provided expression data and patient sample material. This research was supported by the National Natural Science Foundation of China (No. 81672339) and the Project of Scientific Research of Shaanxi (No. 2011KTCL03-15).

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Author notes

  1. These authors contributed equally: Xisheng Yang, Shibin Qu, Lin Wang, Hongtao Zhang, Zhaoxu Yang.

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi’an, China

    Xisheng Yang, Shibin Qu, Lin Wang, Hongtao Zhang, Zhaoxu Yang, Jianlin Wang, Bin Dai, Kaishan Tao, Runze Shang, Zhengcai Liu, Xiao Li, Zhuochao Zhang, Congcong Xia, Ben Ma, Wei Liu, Haimin Li & Kefeng Dou

  2. Section of General Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA

    Shibin Qu

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Correspondence to Haimin Li or Kefeng Dou.

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The authors declare that they have no conflict of interest.

Additional information

RNA Immunoprecipitation (RIP) sequencing The data were deposited in an appropriate public repository (http://pan.baidu.com/s/1boURcZ1; Security code: cprr). This is a permanent publicly accessible links. If necessary, we will upload these data to the GEO database.

This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1038/s41388-023-02648-z"

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Yang, X., Qu, S., Wang, L. et al. RETRACTED ARTICLE: PTBP3 splicing factor promotes hepatocellular carcinoma by destroying the splicing balance of NEAT1 and pre-miR-612. Oncogene 37, 6399–6413 (2018). https://doi.org/10.1038/s41388-018-0416-8

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