MicroRNA-214-3p inhibits the stem-like properties of lung squamous cell cancer by targeting YAP1
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Cancer Cell International Open Access
PRIMARY RESEARCH
MicroRNA‑214‑3p inhibits the stem‑like properties of lung squamous cell cancer by targeting YAP1 Tingting Lu†, Ying Yang†, Ziming Li and Shun Lu*
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. Keywords: MiR-214-3p, YAP1, CSC properties Background Globally, lung cancer (LC) has high mortality rates [1]. Targeted drugs have been developed in lung adenocarcinoma (AC) to inhibit tumor progression, which remarkably changed treatment strategies and brought positive news to patients with EGFR mutation and ALK or ROS1 rearrangements. Compared with AC, the mainstream treatment regimens for lung squamous cell cancer (LSCC) are still platinum-containing chemotherapeutics and immune therapy, and the targeted therapy for *Correspondence: [email protected] † Tingting Lu and Ying Yang contributed equally to this work Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai 200030, People’s Republic of China
advanced LSCC is rare. Therefore, it is urgent to clarify the underlying mechanism of LSCC to develop new and innovative treatment strategies for LSCC patients. MicroRNAs are a cluster of noncoding RNAs that modulate gene expression [2]. Recently, microRNAs became known to regulate tumorigenesis. Increasing evidence has shown that aberrant miRNA expression participates in diverse pathogenic processes, such as tumor apoptosis and CSC properties [3–6]. Moreover, microRNA-controlled cancer stem cells (CSCs) have caused widespread concern as various studies link miRNAs to the characteristics of CSCs and differentiation of embryonic stem cells [7–9]. For instance, miR-205 OE remarkably decreases the proliferation of CSCs in human pancreatic cancer [10] while low expression of miR-613 contributed to the
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