Long noncoding RNAs 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 long noncoding RNA on chromosome 8p12 (termed TSLNC8) that is frequently deleted and down‐regulated 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 and signal transducer and activator of transcription 3 (STAT3) and modulating the STAT3‐Tyr705 and STAT3‐Ser727 phosphorylation levels and STAT3 transcriptional activity, thus resulting in inactivation of the interleukin‐6–STAT3 signaling pathway in HCC cells. Conclusion: TSLNC8 is a promising prognostic predictor for patients with HCC, and the TSLNC8–transketolase–STAT3 axis is a potential therapeutic target for HCC treatment. (Hepatology 2018;67:171‐187).

中文翻译：

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长链非编码 RNA TSLNC8 是一种抑制 IL-6/STAT3 信号通路的肿瘤抑制剂

长链非编码 RNA 可以作为人类癌症中的癌基因或抑癌基因；然而，它们在肝癌发生中的生物学功能和潜在机制在很大程度上是未知的。在这里，我们报告了染色体 8p12 上的一种新型肿瘤抑制长非编码 RNA（称为 TSLNC8），它在肝细胞癌（HCC）组织中经常被删除和下调。TSLNC8 的缺失与 HCC 的恶性特征高度相关，可作为 HCC 患者的预后指标。TSLNC8 在体外和体内显着抑制 HCC 细胞的增殖和转移。TSLNC8 通过与转酮醇酶和信号转导和转录激活因子 3 (STAT3) 竞争性相互作用并调节 STAT3-Tyr705 和 STAT3-Ser727 磷酸化水平和 STAT3 转录活性来发挥其肿瘤抑制活性，从而导致白细胞介素-6-STAT3 失活HCC 细胞中的信号通路。结论：TSLNC8 是 HCC 患者有希望的预后预测因子，TSLNC8-转酮醇酶-STAT3 轴是 HCC 治疗的潜在治疗靶点。（肝病学 2018 年；67：171-187）。