State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Cancer Res. 2017 Nov 1;77(21):5782-5794. doi: 10.1158/0008-5472.CAN-17-0671. Epub 2017 Sep 18.
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. .
长链非编码 RNA（lncRNA）参与肺癌的致癌作用和肿瘤进展。在这里，我们报告了与非小细胞肺癌（NSCLC）转移相关的 lncRNA 特征的鉴定。特别是，在人类 NSCLC 标本中 LINC00963（MetaLnc9）的高表达与预后不良相关，促进了 NSCLC 细胞的迁移和侵袭，并增强了肺转移的形成。机制研究表明，MetaLnc9 与糖酵解激酶 PGK1 相互作用，并防止其在 NSCLC 细胞中的泛素化，导致致癌 AKT/mTOR 信号通路的激活。MetaLnc9 还与 P54nrb/NonO（NONO）相互作用，有助于调节 CREB 转录因子的共激活因子 CRTC 的活性，加强转移的正反馈环。总之，我们的研究结果确立了 MetaLnc9 作为转移的驱动因子和治疗晚期 NSCLC 的候选治疗靶点。
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