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Yu, Tao; Zhao, Yingjun; Hu, Zhixiang; Li, Jing; Chu, Dandan; Zhang, Jiwei; Li, Zhe; Chen, Bing; Zhang, Xiao; Pan, Hongyu; Li, Shengli; Lin, Hechun; Liu, Lei; Yan, Mingxia; He, Xianghuo; Yao, Ming
Cancer research (Chicago, Ill.), 2017-Nov-01, Volume: 77, Issue: 21Journal Article
Long noncoding RNAs (lncRNA) participate in carcinogenesis and tumor progression in lung cancer. Here, we report the identification of a lncRNA signature associated with metastasis of non-small cell lung cancer (NSCLC). In particular, elevated expression of LINC00963 (MetaLnc9) in human NSCLC specimens correlated with poor prognosis, promoted migration and invasion of NSCLC cells , and enhanced lung metastasis formation Mechanistic investigations showed that MetaLnc9 interacted with the glycolytic kinase PGK1 and prevented its ubiquitination in NSCLC cells, leading to activation of the oncogenic AKT/mTOR signaling pathway. MetaLnc9 also interacted with P54nrb/NonO (NONO) to help mediate the activity of CRTC, a coactivator for the transcription factor CREB, reinforcing a positive feedback loop for metastasis. Taken together, our results establish MetaLnc9 as a driver of metastasis and a candidate therapeutic target for treating advanced NSCLC. .
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