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

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.

SUBMITTER: Gong J

PROVIDER: S-EPMC8941509 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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MicroRNA-20a promotes non-small cell lung cancer proliferation by upregulating <i>PD-L1</i> by targeting <i>PTEN</i>.

Gong Jiaomei J Shen Yong Y Jiang Fuguo F Wang Yan Y Chu Lulu L Sun Jinqi J Shen Pengxiao P Chen Maocai M

Oncology letters 20220315 5

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 o ...[more]

PMID: 35350588

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Project description:PurposeHepatocellular carcinoma (HCC), a worldwide leading cause of morbidity and mortality, is the most frequent primary liver tumor. Most HCC patients are diagnosed with advanced liver cancer, resulting in a very low 5-year survival rate. Thus, there is an urgent need for the development of targeted therapies. In this study, we aimed to investigate the effect and mechanism of the miR-20a/EZH1 axis on the proliferation and metastasis of HCC and the inhibitory effect of the EZH1/EZH2 inhibitor UNC1999 on HCC.Materials and methodsThe expression of miR-20a in human HCC tissues and cell lines was detected using quantitative real-time PCR (qRT-PCR). The expressions of proteins were analyzed with immunohistochemistry and Western blotting. Luciferase assay was used to verify whether miR-20a targets EZH1 or EZH2. The effect of miR-20a on HCC progression was studied in vivo and in vitro. The tumor inhibitory effect of UNC1999 was confirmed in vivo. CCK8 assay, wound healing assay, cell migration and invasion assay were used to evaluate the synergistic effect of UNC1999 with sorafenib. RNA sequencing (RNA-seq) was performed to screen the differentially expressed genes in the Huh7 and SMMC7721 cell lines after UNC1999, sorafenib, and combination treatments.ResultsIn this study, miR-20a showed a lower expression in both HCC tissues and cell lines. MiR-20a inhibited the proliferation and migration of SMMC7721 and Huh7 cells. The results of the luciferase assay and Western blot analysis revealed that miR-20a directly targeted EZH1, a histone methyltransferase. We demonstrated that miR-20a negatively regulated the expression of EZH1 and inhibited the proliferation and metastasis of HCC by reducing H3K27 methylation. We found UNC1999 inhibited tumor cells proliferation and enhanced the inhibitory effect of sorafenib.ConclusionWe demonstrated that miR-20a suppresses the tumor proliferation and metastasis in HCC by directly targeting EZH1. UNC1999 can inhibit tumor proliferation in vivo and increase the sensitivity of hepatoma cell lines to sorafenib.

Dataset Information

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

Publications

MicroRNA-20a promotes non-small cell lung cancer proliferation by upregulating <i>PD-L1</i> by targeting <i>PTEN</i>.

Similar Datasets

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