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.

胰腺癌（PC）是世界上最致命的恶性肿瘤之一。染色体8p12上的肿瘤抑制基因长非编码RNA（TSLNC8）是新近鉴定的长非编码RNA（lncRNA），在人类癌症中起着重要作用。但是，TSLNC8在PC进程中的功能和分子机制仍有待阐明。我们的结果显示PC组织和细胞系中TSLNC8表达显着增加。PC组织中TSLNC8表达的上调与TNM分期，远处和淋巴结转移以及PC患者的预后不良密切相关。功能实验表明，TSLNC8在体外促进PC细胞增殖和侵袭，并在体内增强PC生长和转移。从机理上讲，TSLNC8与HuR相关联，促进HuR与CTNNB1 mRNA的结合并增加CTNNB1 mRNA的稳定性，从而激活WNT /β-catenin信号通路。综上所述，我们目前的研究表明，致癌的lncRNA TSLNC8通过HuR介导的CTNNB1的mRNA稳定性正调控PC的生长和转移，扩展了对由lncRNA调控的PC发病机制的理解。