MicroRNA-20a promotes non-small cell lung cancer proliferation by upregulating PD-L1 by targeting PTEN

MicroRNA-20a 通过靶向 PTEN 上调 PD-L1 促进非小细胞肺癌增殖

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作者:Jiaomei Gong, Yong Shen, Fuguo Jiang, Yan Wang, Lulu Chu, Jinqi Sun, Pengxiao Shen, Maocai Chen

Abstract

Non-small cell lung cancer (NSCLC) remains one of the most common malignant tumors worldwide. The aim of the present study was to investigate the possibility of microRNA-20a (miR-20a) as a biomarker and therapeutic target for the diagnosis and treatment of NSCLC. Bioinformatics prediction, together with functional validation, confirmed miR-20a bound to programmed death ligand-1 (PD-L1) 3'-untranslated region to upregulate PD-L1 expression. Both miR-20a and PD-L1 could promote the proliferation of NSCLC cells. The expression level of PD-L1 was controlled by PTEN; however, further upstream regulation of PD-L1 expression was largely unknown. The present study showed that miR-20a could not restore the inhibition of PD-L1 expression levels by PTEN. Knockdown of PTEN expression upregulated the expression level of PD-L1 and promoted the proliferation of NSCLC cells. PTEN negatively regulated the Wnt/β-catenin signaling pathway by inhibiting β-catenin and Cyclin D1. Interestingly, PTEN could reverse miR-20a-mediated proliferation of NSCLC cells and the inhibitory effect was similar to that of XAV-939. miR-20a promotes the proliferation of NSCLC cells by inhibiting the expression level of PTEN and upregulating the expression level of PD-L1. It is suggested that miR-20a could be used as a biomarker and therapeutic target for the treatment of NSCLC.

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