NDLI: miR-193a-3p functions as a tumor suppressor in lung cancer by down-regulating ERBB4.

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miR-193a-3p functions as a tumor suppressor in lung cancer by down-regulating ERBB4.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chen, Xi Liang, Hongwei Zhang, Suyang Zhang, Chen-yu Hou, Dongxia Wang, Xueliang Wang, Nan Li, Jing Zhou, Yong Wang, Wengong Wang, Yanbo Liu, Minghui Yan, Xin Zen, Ke Fu, Zheng
Description	Author Affiliation: Liang H ( From the Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.); Liu M ( From the Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.); Yan X ( the Comprehensive Cancer Center of Drum Tower Hospital affiliated with Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu 210008, China, and.); Zhou Y ( the Department of Thoracic and Cardiovascular surgery, Drum Tower Hospital affiliated with Medical School of Nanjing University, Nanjing, Jiangsu 210008, China.); Wang W ( the Department of Thoracic and Cardiovascular surgery, Drum Tower Hospital affiliated with Medical School of Nanjing University, Nanjing, Jiangsu 210008, China.); Wang X ( From the Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.); Fu Z ( From the Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.); Wang N ( From the Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.); Zhang S ( From the Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.); Wang Y ( From the Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.); Zen K ( From the Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.); Zhang CY ( From the Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.); Hou D ( From the Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China, dxhou128@nju.edu.cn.); Li J ( From the Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China, jingli220@nju.edu.cn.); Chen X ( From the Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China, xichen@nju.edu.cn.)
Abstract	ERBB4, one of four ErbB receptor tyrosine kinase family members, plays an important role in the etiology and progression of lung cancer. In this study, we found that the ERBB4 protein levels were consistently up-regulated in lung cancer tissues, whereas the mRNA levels varied randomly, suggesting that a post-transcriptional mechanism was involved in regulating ERBB4 expression. Because microRNAs are powerful post-transcriptional regulators of gene expression, we used bioinformatic analyses to search for microRNAs that can potentially target ERBB4. We identified specific targeting sites for miR-193a-3p in the 3'-UTR of ERBB4. We further identified an inverse correlation between miR-193a-3p levels and ERBB4 protein levels, but not mRNA levels, in lung cancer tissue samples. By overexpressing or knocking down miR-193a-3p in lung cancer cells, we experimentally confirmed that miR-193a-3p directly recognizes the 3'-UTR of the ERBB4 transcript and regulates ERBB4 expression. Furthermore, the biological consequences of the targeting of ERBB4 by miR-193a-3p were examined in vitro via cell proliferation, invasion, and apoptosis assays and in vivo using a mouse xenograft tumor model. We demonstrated that the repression of ERBB4 by miR-193a-3p suppressed proliferation and invasion and promoted apoptosis in lung cancer cells and that miR-193a-3p exerted an anti-tumor effect by negatively regulating ERBB4 in xenograft mice. Taken together, our findings provide the first clues regarding the role of miR-193a-3p as a tumor suppressor in lung cancer through the inhibition of ERBB4 translation.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	2
Volume Number	290
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2015-01-09
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Apoptosis Genetics Lung Neoplasms MicroRNAs Receptor, ErbB-4 Biosynthesis Animals Cell Line, Tumor Cell Proliferation Gene Expression Regulation, Neoplastic Pathology Mice Protein Biosynthesis Xenograft Model Antitumor Assays Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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miR-193a-3p Functions as a Tumor Suppressor in Lung Cancer by Down-regulating ERBB4*

miR-193a-3p Functions as a Tumor Suppressor in Lung Cancer by Down-regulating ERBB4

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miR-193a-3p functions as a tumor suppressor in lung cancer by down-regulating ERBB4.

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miR-193a-3p Functions as a Tumor Suppressor in Lung Cancer by Down-regulating ERBB4*

miR-193a-3p Functions as a Tumor Suppressor in Lung Cancer by Down-regulating ERBB4

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microRNA-338-3p functions as a tumor suppressor in human non­small­cell lung carcinoma and targets Ras-related protein 14.

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miR-193a-3p functions as a tumor suppressor in lung cancer by down-regulating ERBB4.

MiR203 regulates the proliferation, apoptosis and cell cycle progression of pancreatic cancer cells by targeting Survivin.

microRNA-338-3p functions as a tumor suppressor in human nonsmallcell lung carcinoma and targets Ras-related protein 14.