Lu Tingting, Yang Ying, Li Ziming, Lu Shun
Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai, 200030 People's Republic of China.
Cancer Cell Int. 2020 Aug 27;20:413. doi: 10.1186/s12935-020-01506-2. eCollection 2020.
Emerging evidence reveals that microRNAs (miRNAs) play a crucial role in tumor progression, but the underlying mechanism of microRNAs in lung squamous cell cancer (LSCC) remains unclear.
Western-blotting and quantitative real-time PCR (q-PCR) were carried out to detect mRNA and protein expression. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8), colony-forming assay or sphere-forming assay, respectively.
MiR-214-3p was markedly de-regulated in LSCC tissues and was inversely related to the level of Yes-associated protein1 (YAP1), which is the core transcription regulator of the Hippo signaling pathway. Kaplan-Meier survival curves illustrated that patients with high miR-214-3p expression demonstrated more favorable clinical outcomes. MiR-214-3p overexpression (OE) repressed proliferation and cancer stem-like cells (CSCs) properties in vitro and in vivo xenograft mouse model. Mechanistically, luciferase activity assay revealed that miR-214-3p directly targets YAP1 by specifically binding on the 3' UTR of YAP1.
MiR-214-3p plays a pivotal role in CSCs properties by targeting YAP1, which provides a potential treatment strategy for LSCC patients.
新出现的证据表明，微小RNA（miRNA）在肿瘤进展中起关键作用，但miRNA在肺鳞状细胞癌（LSCC）中的潜在机制仍不清楚。
采用蛋白质免疫印迹法和定量实时聚合酶链反应（q-PCR）检测mRNA和蛋白质表达。分别通过细胞计数试剂盒-8（CCK-8）、集落形成试验或成球试验评估细胞增殖。
MiR-214-3p在LSCC组织中明显失调，且与Yes相关蛋白1（YAP1）水平呈负相关，YAP1是Hippo信号通路的核心转录调节因子。Kaplan-Meier生存曲线表明，miR-214-3p高表达的患者具有更良好的临床结局。MiR-214-3p过表达（OE）在体外和体内异种移植小鼠模型中均抑制了增殖和癌症干细胞（CSC）特性。机制上，荧光素酶活性测定显示miR-214-3p通过特异性结合YAP1的3'非翻译区直接靶向YAP1。
MiR-214-3p通过靶向YAP1在CSC特性中起关键作用，这为LSCC患者提供了一种潜在的治疗策略。
