MicroRNA-561 Affects Proliferation and Cell Cycle Transition Through PTEN/AKT Signaling Pathway by Targeting P-REX2a in NSCLC
| Autor: | Ting Wei, Zi-Jun Liao, Zheng Zhao, Yanbing Zhang, Hai-Feng Sun, Jiequn Ma, Kejun Nan, Qi Zheng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Cancer Research Proliferation Non-small cell lung cancer (NSCLC) Apoptosis medicine.disease_cause Article Disease-Free Survival 03 medical and health sciences Phosphatidylinositol 3-Kinases 0302 clinical medicine Cell Movement Carcinoma Non-Small-Cell Lung Cell Line Tumor microRNA medicine PTEN Gene silencing Guanine Nucleotide Exchange Factors Humans Cell Proliferation biology Chemistry Akt/PKB signaling pathway Cell growth Cell Cycle PTEN Phosphohydrolase General Medicine Cell cycle Middle Aged miR-561 Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Oncology Tumor progression 030220 oncology & carcinogenesis Cancer research biology.protein Female Carcinogenesis P-REX2a Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Oncology Research |
| ISSN: | 1555-3906 0965-0407 |
| Popis: | MicroRNAs (miRNAs) play crucial roles in tumorigenesis and tumor progression. miR-561 has been reported to be downregulated in gastric cancer and affects cancer cell proliferation and metastasis. However, the role and underlying molecular mechanism of miR-561 in human non-small cell lung cancer (NSCLC) remain unknown and need to be further elucidated. In this study, we discovered that miR-561 expression was downregulated in human NSCLC tissues and cell lines. The overexpression of miR-561 inhibited NSCLC cell proliferation and cell cycle G1/S transition and induced apoptosis. The inhibition of miR-561 facilitated cell proliferation and G1/S transition and suppressed apoptosis. miR-561 expression was inversely correlated with P-REX2a expression in NSCLC tissues. P-REX2a was confirmed to be a direct target of miR-561 using a luciferase reporter assay. The overexpression of miR-561 decreased P-REX2a expression, and the suppression of miR-561 increased P-REX2a expression. Particularly, P-REX2a silencing recapitulated the cellular and molecular effects observed upon miR-561 overexpression, and P-REX2a overexpression counteracted the effects of miR-561 overexpression on NSCLC cells. Moreover, both exogenous expression of miR-561 and silencing of P-REX2a resulted in suppression of the PTEN/AKT signaling pathway. Our study demonstrates that miR-561 inhibits NSCLC cell proliferation and G1/S transition and induces apoptosis through suppression of the PTEN/AKT signaling pathway by targeting P-REX2a. These findings indicate that miR-561 plays a significant role in NSCLC progression and serves as a potential therapeutic target for NSCLC. |
| Databáze: | OpenAIRE |
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