Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
Department of Biology, School of Basic Medical Science, Guangdong Medical University, Zhanjiang, Guangdong, China.
Oncogene. 2021 May;40(19):3449-3459. doi: 10.1038/s41388-021-01769-7. Epub 2021 Apr 15.
Long non-coding RNAs (lncRNAs) are emerging as a new class of regulators for a variety of biological processes and have been suggested to play pivotal roles in cancer development and progression. Our current study found that a lncRNA, designated enhancing IL-6/STAT3 signaling activation (LEISA, ENST00000603468), functioned as an oncogenic lncRNA in lung adenocarcinoma (LAD), a major form of non-small cell lung carcinoma, which is one of the most frequently diagnosed malignancies with high morbidity and mortality worldwide, and was involved in the regulation of STAT3 induced IL-6 transcription. Our data showed that LEISA was highly expressed in, and correlated with the clinical progression and prognosis of LAD. Ectopic expression of LEISA promoted the proliferation and suppressed apoptosis of LAD cells in vitro and in vivo. Mechanistically, we demonstrated that LEISA recruited STAT3 to bind the promoter of IL-6 and upregulated IL-6 expression. Taken together, our work identifies LEISA as a potential diagnostic biomarker and therapeutic target for LAD.
长非编码 RNA（lncRNAs）作为一类新的调控因子，在多种生物学过程中发挥着重要作用，并被认为在癌症的发生和发展中起着关键作用。我们的研究发现，一种长非编码 RNA，命名为增强 IL-6/STAT3 信号激活（LEISA，ENST00000603468），在肺腺癌（LAD）中作为一种致癌性 lncRNA 发挥作用，肺腺癌是一种非小细胞肺癌的主要形式，是世界上最常见的高发病率和高死亡率的恶性肿瘤之一，参与了 STAT3 诱导的 IL-6 转录的调节。我们的数据表明，LEISA 在肺腺癌中表达水平较高，与临床进展和预后相关。异位表达 LEISA 促进了体外和体内肺腺癌细胞的增殖，抑制了细胞凋亡。从机制上讲，我们证明了 LEISA 募集 STAT3 结合 IL-6 启动子并上调 IL-6 的表达。总之，我们的工作确定 LEISA 是肺腺癌的一个潜在的诊断生物标志物和治疗靶点。
