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MicroRNA-561 Affects Proliferation and Cell Cycle Transition Through PTEN/AKT Signaling Pathway by Targeting P-REX2a in NSCLC

ZiJun Liao*†, Qi Zheng, Ting Wei, YanBing Zhang, JieQun Ma, Zheng Zhao§, HaiFeng Sun§, KeJun Nan*

* Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, P.R. China
† First Department of Medical Oncology, Affiliated Shaanxi Provincial Cancer Hospital, College of Medicine, Xi’an Jiaotong University, Shaanxi Province, P.R. China
‡ Department of Ophthalmology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, P.R. China
§ Third Department of Medical Oncology, Affiliated Shaanxi Provincial Cancer Hospital, College of Medicine, Xi’an Jiaotong University, Shaanxi Province, P.R. China

Oncology Research 2020, 28(2), 147-159. https://doi.org/10.3727/096504019X15732109856009

Abstract

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.

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APA Style
Liao, Z., Zheng, Q., Wei, T., Zhang, Y., Ma, J. et al. (2020). Microrna-561 affects proliferation and cell cycle transition through PTEN/AKT signaling pathway by targeting p-rex2a in NSCLC. Oncology Research, 28(2), 147-159. https://doi.org/10.3727/096504019X15732109856009
Vancouver Style
Liao Z, Zheng Q, Wei T, Zhang Y, Ma J, Zhao Z, et al. Microrna-561 affects proliferation and cell cycle transition through PTEN/AKT signaling pathway by targeting p-rex2a in NSCLC. Oncol Res. 2020;28(2):147-159 https://doi.org/10.3727/096504019X15732109856009
IEEE Style
Z. Liao et al., "MicroRNA-561 Affects Proliferation and Cell Cycle Transition Through PTEN/AKT Signaling Pathway by Targeting P-REX2a in NSCLC," Oncol. Res., vol. 28, no. 2, pp. 147-159. 2020. https://doi.org/10.3727/096504019X15732109856009



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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