Oncotarget

Research Papers:

BAP1 suppresses lung cancer progression and is inhibited by miR-31

Mengchao Yu, Hongwei Liang, Zheng Fu, Xueliang Wang, Zhicong Liao, Yong Zhou, Yanqing Liu, Yanbo Wang, Yeting Hong, Xinyan Zhou, Xin Yan, Min Yu, Miao Ma, Weijie Zhang, Baoliang Guo, Jianguo Zhang, Ke Zen, Chen-Yu Zhang, Tao Wang, Qipeng Zhang and Xi Chen _

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Oncotarget. 2016; 7:13742-13753. https://doi.org/10.18632/oncotarget.7328

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Abstract

Mengchao Yu1,*, Hongwei Liang1,*, Zheng Fu1,*, Xueliang Wang1, Zhicong Liao2, Yong Zhou2, Yanqing Liu1, Yanbo Wang1, Yeting Hong1, Xinyan Zhou1, Xin Yan3, Min Yu3, Miao Ma3, Weijie Zhang4, Baoliang Guo5, Jianguo Zhang5, Ke Zen1, Chen-Yu Zhang1, Tao Wang2 , Qipeng Zhang1 and Xi Chen1

1 State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China

2 Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University and Nanjing Multi-Center Biobank, Nanjing, Jiangsu, China

3 Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China

4 Department of General Surgery, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China

5 Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China

* These authors have contributed equally to this work

Correspondence to:

Xi Chen, email:

Qipeng Zhang, email:

Tao Wang, email:

Keywords: lung cancer, BAP1, miR-31, proliferation, apoptosis

Received: November 04, 2015 Accepted: January 29, 2016 Published: February 11, 2016

Abstract

BRCA1-associated protein-1 (BAP1) is an important nuclear-localized deubiquitinating enzyme that serves as a tumor suppressor in lung cancer; however, its function and its regulation are largely unknown. In this study, we found that BAP1 protein levels were dramatically diminished in lung cancer tissues while its mRNA levels did not differ significantly, suggesting that a post-transcriptional mechanism was involved in BAP1 regulation. Because microRNAs (miRNAs) are powerful post-transcriptional regulators of gene expression, we used bioinformatic analyses to search for miRNAs that could potentially bind BAP1. We predicted and experimentally validated miR-31 as a direct regulator of BAP1. Moreover, we showed that miR-31 promoted proliferation and suppressed apoptosis in lung cancer cells and accelerated the development of tumor growth in xenograft mice by inhibiting BAP1. Taken together, this study highlights an important role for miR-31 in the suppression of BAP1 in lung cancer cells and may provide insights into the molecular mechanisms of lung carcinogenesis.


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