Open Access
ARTICLE
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.
Keywords
Cite This Article
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.