MicroRNA‐7‐5p induces cell growth inhibition, cell cycle arrest and apoptosis by targeting PAK2 in non‐small cell lung cancer

MicroRNAs (miR) are known to be critical regulators in tumor progression. miR‐7‐5p was reported to be involved in several cancers, including glioblastoma, cervical cancer, and melanoma, but its prognostic value and biological function in non‐small‐cell lung cancer (NSCLC) remain unclear. In this stu...

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Main Authors: Qin Li, Xingping Wu, Lin Guo, Jiaxin Shi, Jiashu Li
Format: Article
Language:English
Published: Wiley 2019-11-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.12738
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author Qin Li
Xingping Wu
Lin Guo
Jiaxin Shi
Jiashu Li
author_facet Qin Li
Xingping Wu
Lin Guo
Jiaxin Shi
Jiashu Li
author_sort Qin Li
collection DOAJ
description MicroRNAs (miR) are known to be critical regulators in tumor progression. miR‐7‐5p was reported to be involved in several cancers, including glioblastoma, cervical cancer, and melanoma, but its prognostic value and biological function in non‐small‐cell lung cancer (NSCLC) remain unclear. In this study, using quantitative real‐time PCR analysis, we found that miR‐7‐5p was significantly downregulated in NSCLC tissues and cell lines. Lower miR‐7‐5p expression was associated with tumor–node–metastasis stage and tumor size by chi‐squared test. Deceased miR‐7‐5p expression was associated with a worse prognosis in patients with NSCLC using Kaplan–Meier survival analysis and multivariate Cox regression analysis. Experiments in NSCLC cell lines (A549 and H1299) demonstrated that upregulation of miR‐7‐5p significantly suppressed cell proliferation, but induced cell cycle G0/G1 phase arrest and apoptosis using Cell Counting Kit‐8, colony formation, and flow cytometry analysis. Through loss‐of‐function assays, we further demonstrated that downregulation of miR‐7‐5p promoted cell proliferation and cell cycle G1/S transition, but decreased cell apoptosis in SPC‐A1 cells. Furthermore, P21‐activated kinase 2 (PAK2) was predicted and confirmed as a direct target gene of miR‐7‐5p in NSCLC cells by luciferase reporter assay. In addition, we found PAK2 overexpression could partially reverse the effects of miR‐7‐5p on cell proliferation, cell cycle distribution, and apoptosis. We thus concluded that lower expression of miR‐7‐5p was associated with poor prognosis and NSCLC progression by directly targeting PAK2.
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spelling doaj.art-98da3646d40b4d39bdf2256a902bb0212022-12-21T23:03:31ZengWileyFEBS Open Bio2211-54632019-11-019111983199310.1002/2211-5463.12738MicroRNA‐7‐5p induces cell growth inhibition, cell cycle arrest and apoptosis by targeting PAK2 in non‐small cell lung cancerQin Li0Xingping Wu1Lin Guo2Jiaxin Shi3Jiashu Li4Department of Respiration Xuzhou Medical University Affiliated Hospital of Lianyungang ChinaDepartment of Respiration Xuzhou Medical University Affiliated Hospital of Lianyungang ChinaDepartment of Respiration Xuzhou Medical University Affiliated Hospital of Lianyungang ChinaDepartment of Respiration Xuzhou Medical University Affiliated Hospital of Lianyungang ChinaDepartment of Respiration Xuzhou Medical University Affiliated Hospital of Lianyungang ChinaMicroRNAs (miR) are known to be critical regulators in tumor progression. miR‐7‐5p was reported to be involved in several cancers, including glioblastoma, cervical cancer, and melanoma, but its prognostic value and biological function in non‐small‐cell lung cancer (NSCLC) remain unclear. In this study, using quantitative real‐time PCR analysis, we found that miR‐7‐5p was significantly downregulated in NSCLC tissues and cell lines. Lower miR‐7‐5p expression was associated with tumor–node–metastasis stage and tumor size by chi‐squared test. Deceased miR‐7‐5p expression was associated with a worse prognosis in patients with NSCLC using Kaplan–Meier survival analysis and multivariate Cox regression analysis. Experiments in NSCLC cell lines (A549 and H1299) demonstrated that upregulation of miR‐7‐5p significantly suppressed cell proliferation, but induced cell cycle G0/G1 phase arrest and apoptosis using Cell Counting Kit‐8, colony formation, and flow cytometry analysis. Through loss‐of‐function assays, we further demonstrated that downregulation of miR‐7‐5p promoted cell proliferation and cell cycle G1/S transition, but decreased cell apoptosis in SPC‐A1 cells. Furthermore, P21‐activated kinase 2 (PAK2) was predicted and confirmed as a direct target gene of miR‐7‐5p in NSCLC cells by luciferase reporter assay. In addition, we found PAK2 overexpression could partially reverse the effects of miR‐7‐5p on cell proliferation, cell cycle distribution, and apoptosis. We thus concluded that lower expression of miR‐7‐5p was associated with poor prognosis and NSCLC progression by directly targeting PAK2.https://doi.org/10.1002/2211-5463.12738cell proliferationmiR‐7‐5pnon‐small‐cell lung cancerPAK2
spellingShingle Qin Li
Xingping Wu
Lin Guo
Jiaxin Shi
Jiashu Li
MicroRNA‐7‐5p induces cell growth inhibition, cell cycle arrest and apoptosis by targeting PAK2 in non‐small cell lung cancer
FEBS Open Bio
cell proliferation
miR‐7‐5p
non‐small‐cell lung cancer
PAK2
title MicroRNA‐7‐5p induces cell growth inhibition, cell cycle arrest and apoptosis by targeting PAK2 in non‐small cell lung cancer
title_full MicroRNA‐7‐5p induces cell growth inhibition, cell cycle arrest and apoptosis by targeting PAK2 in non‐small cell lung cancer
title_fullStr MicroRNA‐7‐5p induces cell growth inhibition, cell cycle arrest and apoptosis by targeting PAK2 in non‐small cell lung cancer
title_full_unstemmed MicroRNA‐7‐5p induces cell growth inhibition, cell cycle arrest and apoptosis by targeting PAK2 in non‐small cell lung cancer
title_short MicroRNA‐7‐5p induces cell growth inhibition, cell cycle arrest and apoptosis by targeting PAK2 in non‐small cell lung cancer
title_sort microrna 7 5p induces cell growth inhibition cell cycle arrest and apoptosis by targeting pak2 in non small cell lung cancer
topic cell proliferation
miR‐7‐5p
non‐small‐cell lung cancer
PAK2
url https://doi.org/10.1002/2211-5463.12738
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