Long noncoding RNA TSLNC8 enhances pancreatic cancer aggressiveness by regulating CTNNB1 expression via association with
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RESEARCH ARTICLE
Long noncoding RNA TSLNC8 enhances pancreatic cancer aggressiveness by regulating CTNNB1 expression via association with HuR Wei Chai1 · Ruhai Liu1 · Fengshan Li1 · Zhiquan Zhang1 · Bao Lei1 Received: 27 July 2020 / Accepted: 4 September 2020 © Japan Human Cell Society 2020
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. Keywords HuR · mRNA stability · Posttranscriptional regulation · wnt/β-catenin signaling pathway 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 Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13577-020-00429-4) contains supplementary material, which is available to authorized users. * Wei Chai [email protected] 1
Department of the First General Surgery, Cangzhou Central Hospital, No. 16, Xinhua West road, Cangzhou 061000, Hebei, China
Introduction Pancreatic cancer (PC) is one of the most lethal malignancies worldwide, which causes more than 331,000 deaths per year [1]. The risk factors of PC includes smoking, obesity, genetics, diabetes mellitus, alcohol use and physical inactivity [2]. Due to the atypical symptoms and limitation of diagnostic techniques of PC, most of the patients were diagnosed at an advanced stage. Despite the great improvement of comprehensive therapy of PC over the past decades, the 5-year survival rate of PC patients remains only approximately 7% [3, 4]. Therefore, revealing the underlying mechanism of PC progression are urgently needed for the identification of novel diagnostic and therapeutic targets for PC. Long noncoding RNAs (lncRNAs) belong to a subfam
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