miR-146a-5p Plays an Oncogenic Role in NSCLC via Suppression of TRAF6

Non-small cell lung cancer (NSCLC) is the most deadly cancer in the world due to its often delayed diagnosis. Identification of biomarkers with high sensitivity, specificity, and accessibility for early detection, such as circulating microRNAs, is therefore of utmost importance. In the present study...

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Main Authors: Xiangdong Liu, Bo Liu, Ruihua Li, Fei Wang, Ning Wang, Maihe Zhang, Yang Bai, Jin Wu, Liping Liu, Dongyu Han, Zhiguang Li, Bin Feng, Guangbiao Zhou, Shujing Wang, Li Zeng, Jian Miao, Yiqun Yao, Bin Liang, Lin Huang, Qi Wang, Yingjie Wu
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-09-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fcell.2020.00847/full
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author Xiangdong Liu
Xiangdong Liu
Xiangdong Liu
Bo Liu
Bo Liu
Bo Liu
Ruihua Li
Fei Wang
Fei Wang
Fei Wang
Ning Wang
Ning Wang
Ning Wang
Maihe Zhang
Maihe Zhang
Maihe Zhang
Yang Bai
Yang Bai
Yang Bai
Jin Wu
Jin Wu
Jin Wu
Liping Liu
Liping Liu
Liping Liu
Dongyu Han
Dongyu Han
Dongyu Han
Zhiguang Li
Bin Feng
Guangbiao Zhou
Shujing Wang
Shujing Wang
Li Zeng
Li Zeng
Li Zeng
Jian Miao
Yiqun Yao
Bin Liang
Lin Huang
Lin Huang
Qi Wang
Yingjie Wu
Yingjie Wu
Yingjie Wu
Yingjie Wu
Yingjie Wu
author_facet Xiangdong Liu
Xiangdong Liu
Xiangdong Liu
Bo Liu
Bo Liu
Bo Liu
Ruihua Li
Fei Wang
Fei Wang
Fei Wang
Ning Wang
Ning Wang
Ning Wang
Maihe Zhang
Maihe Zhang
Maihe Zhang
Yang Bai
Yang Bai
Yang Bai
Jin Wu
Jin Wu
Jin Wu
Liping Liu
Liping Liu
Liping Liu
Dongyu Han
Dongyu Han
Dongyu Han
Zhiguang Li
Bin Feng
Guangbiao Zhou
Shujing Wang
Shujing Wang
Li Zeng
Li Zeng
Li Zeng
Jian Miao
Yiqun Yao
Bin Liang
Lin Huang
Lin Huang
Qi Wang
Yingjie Wu
Yingjie Wu
Yingjie Wu
Yingjie Wu
Yingjie Wu
author_sort Xiangdong Liu
collection DOAJ
description Non-small cell lung cancer (NSCLC) is the most deadly cancer in the world due to its often delayed diagnosis. Identification of biomarkers with high sensitivity, specificity, and accessibility for early detection, such as circulating microRNAs, is therefore of utmost importance. In the present study, we identified a significantly higher expression of miR-146a-5p in the serum and tissue samples of NSCLC patients than that of the healthy controls. In parallel, miR-146a-5p was also highly expressed in three human NSCLC adenocarcinoma-cell lines (A549, H1299, and H1975) compared to the human bronchial epithelium cell line (HBE). By dual-luciferase reporter assay and manipulation of the expressions of miR-146a-5p and its target gene, tumor necrosis factor receptor-associated factor 6 (TRAF6), we showed that the functional effects of miR-146a-5p on NSCLC cell survival and migration were mediated by direct binding to and suppression of TRAF6. Overexpression of TRAF6 sufficiently reversed miR-146a-5p-induced cancer cell proliferation, migration, and apoptosis resistance. Our data implied that miR-146a-5p/TRAF6/NF-κB-p65 axis could be a promising diagnostic marker and a therapeutic target for NSCLC.
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spelling doaj.art-4dbe469c23744579b8cc48d3c4704af62022-12-21T21:11:22ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-09-01810.3389/fcell.2020.00847542594miR-146a-5p Plays an Oncogenic Role in NSCLC via Suppression of TRAF6Xiangdong Liu0Xiangdong Liu1Xiangdong Liu2Bo Liu3Bo Liu4Bo Liu5Ruihua Li6Fei Wang7Fei Wang8Fei Wang9Ning Wang10Ning Wang11Ning Wang12Maihe Zhang13Maihe Zhang14Maihe Zhang15Yang Bai16Yang Bai17Yang Bai18Jin Wu19Jin Wu20Jin Wu21Liping Liu22Liping Liu23Liping Liu24Dongyu Han25Dongyu Han26Dongyu Han27Zhiguang Li28Bin Feng29Guangbiao Zhou30Shujing Wang31Shujing Wang32Li Zeng33Li Zeng34Li Zeng35Jian Miao36Yiqun Yao37Bin Liang38Lin Huang39Lin Huang40Qi Wang41Yingjie Wu42Yingjie Wu43Yingjie Wu44Yingjie Wu45Yingjie Wu46Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian, ChinaNational Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian, ChinaLiaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian, ChinaInstitute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian, ChinaNational Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian, ChinaLiaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian, ChinaDepartment of Clinical Laboratory, Second Affiliated Hospital of Dalian Medical University, Liaoning, ChinaInstitute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian, ChinaNational Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian, ChinaLiaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian, ChinaInstitute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian, ChinaNational Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian, ChinaLiaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian, ChinaInstitute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian, ChinaNational Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian, ChinaLiaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian, ChinaInstitute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian, ChinaNational Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Liaoning, ChinaInstitute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian, ChinaNational Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian, ChinaLiaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian, ChinaInstitute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian, ChinaNational Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian, ChinaLiaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian, ChinaInstitute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian, ChinaNational Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian, ChinaLiaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian, ChinaCenter of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, ChinaDepartment of Biotechnology, Dalian Medical University, Dalian, ChinaInstitute of Zoology, Chinese Academy of Sciences, Beijing, ChinaLiaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian, ChinaDepartment of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian, ChinaInstitute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian, ChinaNational Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian, ChinaLiaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Liaoning, China0Department of Thyroid and Breast Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China1School of Life Sciences, Yunnan University, Kunming, ChinaLiaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian, China2Department of Pathophysiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China3Department of Respiratory Medicine, Second Affiliated Hospital of Dalian Medical University, Liaoning, ChinaInstitute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian, ChinaNational Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian, ChinaLiaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian, China4Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY, United States5Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesNon-small cell lung cancer (NSCLC) is the most deadly cancer in the world due to its often delayed diagnosis. Identification of biomarkers with high sensitivity, specificity, and accessibility for early detection, such as circulating microRNAs, is therefore of utmost importance. In the present study, we identified a significantly higher expression of miR-146a-5p in the serum and tissue samples of NSCLC patients than that of the healthy controls. In parallel, miR-146a-5p was also highly expressed in three human NSCLC adenocarcinoma-cell lines (A549, H1299, and H1975) compared to the human bronchial epithelium cell line (HBE). By dual-luciferase reporter assay and manipulation of the expressions of miR-146a-5p and its target gene, tumor necrosis factor receptor-associated factor 6 (TRAF6), we showed that the functional effects of miR-146a-5p on NSCLC cell survival and migration were mediated by direct binding to and suppression of TRAF6. Overexpression of TRAF6 sufficiently reversed miR-146a-5p-induced cancer cell proliferation, migration, and apoptosis resistance. Our data implied that miR-146a-5p/TRAF6/NF-κB-p65 axis could be a promising diagnostic marker and a therapeutic target for NSCLC.https://www.frontiersin.org/article/10.3389/fcell.2020.00847/fullapoptosismiR-146a-5pmigrationnon-small cell lung cancerTRAF6
spellingShingle Xiangdong Liu
Xiangdong Liu
Xiangdong Liu
Bo Liu
Bo Liu
Bo Liu
Ruihua Li
Fei Wang
Fei Wang
Fei Wang
Ning Wang
Ning Wang
Ning Wang
Maihe Zhang
Maihe Zhang
Maihe Zhang
Yang Bai
Yang Bai
Yang Bai
Jin Wu
Jin Wu
Jin Wu
Liping Liu
Liping Liu
Liping Liu
Dongyu Han
Dongyu Han
Dongyu Han
Zhiguang Li
Bin Feng
Guangbiao Zhou
Shujing Wang
Shujing Wang
Li Zeng
Li Zeng
Li Zeng
Jian Miao
Yiqun Yao
Bin Liang
Lin Huang
Lin Huang
Qi Wang
Yingjie Wu
Yingjie Wu
Yingjie Wu
Yingjie Wu
Yingjie Wu
miR-146a-5p Plays an Oncogenic Role in NSCLC via Suppression of TRAF6
Frontiers in Cell and Developmental Biology
apoptosis
miR-146a-5p
migration
non-small cell lung cancer
TRAF6
title miR-146a-5p Plays an Oncogenic Role in NSCLC via Suppression of TRAF6
title_full miR-146a-5p Plays an Oncogenic Role in NSCLC via Suppression of TRAF6
title_fullStr miR-146a-5p Plays an Oncogenic Role in NSCLC via Suppression of TRAF6
title_full_unstemmed miR-146a-5p Plays an Oncogenic Role in NSCLC via Suppression of TRAF6
title_short miR-146a-5p Plays an Oncogenic Role in NSCLC via Suppression of TRAF6
title_sort mir 146a 5p plays an oncogenic role in nsclc via suppression of traf6
topic apoptosis
miR-146a-5p
migration
non-small cell lung cancer
TRAF6
url https://www.frontiersin.org/article/10.3389/fcell.2020.00847/full
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