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Long noncoding RNA TSLNC8 enhances pancreatic cancer aggressiveness by regulating CTNNB1 expression via association with HuR

Human Cell volume 34, pages 165–176 (2021)Cite this article

Abstract

Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. Tumor suppressor long noncoding RNA on chromosome 8p12 (TSLNC8) is a newly identified long noncoding RNA (lncRNA) and play an important role in human cancers. However, the function and molecular mechanism of TSLNC8 in PC progression remain to be elucidated. Our results showed a significant increase of TSLNC8 expression in PC tissues and cell lines. Upregulation of TSLNC8 expression in PC tissues was closely correlated with TNM stage, distant and lymph node metastasis, and poor prognosis of PC patients. Functional experiments demonstrated that TSLNC8 promoted PC cells proliferation and invasion in vitro, and enhanced PC growth and metastasis in vivo. Mechanistically, TSLNC8 associated with HuR, promoted the binding of HuR with CTNNB1 mRNA and increased the stability of CTNNB1 mRNA, thus activating WNT/β-catenin signaling pathway. Taken together, our present study revealed that oncogenic lncRNA TSLNC8 positively regulate PC growth and metastasis via HuR-mediated mRNA stability of CTNNB1, extending the understanding of PC pathogenesis regulated by lncRNAs.

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Abbreviations

PC:

Pancreatic cancer

lncRNAs:

Long noncoding RNAs

EMT:

Epithelia-mesenchymal transition

YB1:

Y-box protein

HCC:

Hepatocellular carcinoma

termed TSLNC8:

Tumor suppressor long noncoding RNA on chromosome 8p12

CCK-8:

Cell counting Kit-8

qRT-PCR:

Quantitative real-time PCR

SDS-PAGE:

Sodium dodecyl sulfate–polyacrylamide gel electrophoresis

ECL:

Enhanced chemiluminescence

RIP:

RNA immunoprecipitation

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Funding

This work was supported by the Natural Funding of Cangzhou Central Hospital (Grant no. 201808).

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  1. Department of the First General Surgery, Cangzhou Central Hospital, No. 16, Xinhua West road, Cangzhou, 061000, Hebei, China

    Wei Chai, Ruhai Liu, Fengshan Li, Zhiquan Zhang & Bao Lei

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  1. Wei Chai
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Correspondence to Wei Chai.

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The present study was approved by the Ethics Committee of Cangzhou Central Hospital (Approval number: 202005-08). The research has been carried out in accordance with the World Medical Association Declaration of Helsinki.

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Chai, W., Liu, R., Li, F. et al. Long noncoding RNA TSLNC8 enhances pancreatic cancer aggressiveness by regulating CTNNB1 expression via association with HuR. Human Cell 34, 165–176 (2021). https://doi.org/10.1007/s13577-020-00429-4

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  • DOI: https://doi.org/10.1007/s13577-020-00429-4

Keywords

  • HuR
  • mRNA stability
  • Posttranscriptional regulation
  • wnt/β-catenin signaling pathway