Cheng Zhuoan, Lu Chunlai, Wang Hui, Wang Ning, Cui Shaohua, Yu Chengtao, Wang Cun, Zuo Qiaozhu, Wang Siying, Lv Yuanyuan, Yao Ming, Jiang Liyan, Qin Wenxin
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
Department of thoracic surgery, Zhongshan hospital, Fudan university, Shanghai, 200032, China.
Cancer Lett. 2022 Apr 10;531:1-13. doi: 10.1016/j.canlet.2022.01.031. Epub 2022 Jan 29.
Lung cancer is the most common cancer and the leading cause of cancer deaths worldwide. In addition to coding genes, the contribution of long noncoding RNA (lncRNA) to non-small cell lung cancer (NSCLC) remains unclear. Here, we explored lncRNA expression profiles by Affymetrix Gene Chip Human Transcriptome Array 2.0 in 37 paired samples of tumorous NSCLC tissues and adjacent nontumorous tissues. We showed that LHFPL3-AS2 is a novel lncRNA, significantly decreased in NSCLC tissues. LHFPL3-AS2 was further validated in an additional 93 paired samples of NSCLC. Low levels of LHFPL3-AS2 expression were highly correlated with poor overall survival, TNM stage, and metastasis of NSCLC patients. Enhanced expression of LHFPL3-AS2 inhibited NSCLC invasion and metastasis in vitro and in vivo. Moreover, downregulation of LHFPL3-AS2 reduced its specific interaction with SFPQ, resulting in more SFPQ binding to the promoter of TXNIP and causing the transcriptional repression of TXNIP, thus finally promoting the migration and invasion of NSCLC cells. Furthermore, LHFPL3-AS2 was shown to be regulated by EGR1 under hypoxia.
肺癌是全球最常见的癌症，也是癌症死亡的主要原因。除了编码基因外，长链非编码RNA（lncRNA）对非小细胞肺癌（NSCLC）的作用仍不清楚。在此，我们通过Affymetrix基因芯片人类转录组阵列2.0对37对NSCLC肿瘤组织和相邻非肿瘤组织样本进行了lncRNA表达谱分析。我们发现LHFPL3-AS2是一种新型lncRNA，在NSCLC组织中显著降低。LHFPL3-AS2在另外93对NSCLC样本中得到进一步验证。LHFPL3-AS2低表达水平与NSCLC患者的总生存期差、TNM分期和转移高度相关。LHFPL3-AS2的过表达在体外和体内均抑制NSCLC的侵袭和转移。此外，LHFPL3-AS2的下调减少了其与SFPQ的特异性相互作用，导致更多SFPQ与TXNIP启动子结合并引起TXNIP的转录抑制，最终促进NSCLC细胞的迁移和侵袭。此外，研究表明LHFPL3-AS2在缺氧条件下受EGR1调控。
