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MicroRNA-214-3p inhibits the stem-like properties of lung squamous cell cancer by targeting YAP1

机译:MicroRNA-214-3P通过靶向YAP1抑制肺鳞状细胞癌的干燥性质

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摘要

Abstract Background 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. Method 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. Results 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. Conclusion MiR-214-3p plays a pivotal role in CSCs properties by targeting YAP1, which provides a potential treatment strategy for LSCC patients.
机译:摘要背景新兴的证据表明,MicroRNA(miRNA)在肿瘤进展中发挥着至关重要的作用,但MicroRNA在肺鳞状细胞癌(LSCC)中的潜在机制仍不清楚。方法进行蛋白质印迹和定量实时PCR(Q-PCR)以检测mRNA和蛋白质表达。通过细胞计数试剂盒-8(CCK-8),菌落形成测定或球形测定法评估细胞增殖。结果MIR-214-3P在LSCC组织中显着降低,与河马信号通路的核心转录调节器相反,与河马信号传导途径的核心转录调节器相反。 Kaplan-Meier生存曲线说明了高MiR-214-3P表达的患者表现出更有利的临床结果。 MiR-214-3P过表达(OE)在体外和体内异种移植小鼠模型中抑制增殖和癌症干细胞(CSCs)性质。机械地,荧光素酶活性测定显示MIR-214-3P通过在YAP1的3'UTR上特异性结合直接靶向YAP1。结论MIR-214-3P通过靶向YAP1在CSCS性质中发挥关键作用,为LSCC患者提供了潜在的治疗策略。

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