Jiwei Zhang1, Zhe Li1, Longzi Liu2, Qifeng Wang1, Shengli Li1, Di Chen1, Zhixiang Hu1, Tao Yu3, Jie Ding1, Jinjun Li3, Ming Yao3, Shenglin Huang1, Yingjun Zhao1, Xianghuo He1,4. 1. Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China. 2. Liver Cancer Institute, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. 3. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 4. Collaborative Innovation Center for Cancer Medicine, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Abstract
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).
Long noncoding RNAs can serve as oncogenes or tumor suppressors in humancancer; 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).
Authors: Sarah B Lazar; Lorinc Pongor; Xiao Ling Li; Ioannis Grammatikakis; Bruna R Muys; Emily A Dangelmaier; Christophe E Redon; Sang-Min Jang; Robert L Walker; Wei Tang; Stefan Ambs; Curtis C Harris; Paul S Meltzer; Mirit I Aladjem; Ashish Lal Journal: Mol Cell Biol Date: 2020-10-13 Impact factor: 4.272