Long Noncoding RNA TSLNC8 Is a Tumor Suppressor that Inactivates the IL-6/STAT3 Signaling Pathway

Abstract

Long noncoding RNAs (lncRNAs) can serve as oncogenes or tumor suppressors in human cancer; however, their biological functions and underlying mechanism in hepatocarcinogenesis are largely unknown. Here, we report a novel tumor suppressor lncRNA on chromosome 8p12 (termed TSLNC8) that is frequently deleted and downregulated in hepatocellular carcinoma (HCC) tissues. The loss of TSLNC8 is highly associated with the malignant features of HCC and serves as a prognostic indicator for HCC patients. TSLNC8 significantly suppresses the proliferation and metastasis of HCC cells in vitro and in vivo. TSLNC8 exerts its tumor suppressive activity by competitively interacting with transketolase (TKT) and STAT3, and modulating the STAT3-Tyr705 and STAT3-Ser727 phosphorylation levels and STAT3 transcriptional activity, thus resulting in the inactivation of the IL-6/STAT3 signaling pathway in HCC cells. Conclusion: TSLNC8 is a promising prognostic predictor for patients with HCC, and the newly identified TSLNC8-TKT-STAT3 axis is a potential therapeutic target for HCC treatment. This article is protected by copyright. All rights reserved.

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