title: BAP1 suppresses lung cancer progression and is inhibited by miR-31.
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.
authors.affiliation: 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.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fu
authors.affiliation: 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.
authors.forename: Xueliang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University and Nanjing Multi-Center Biobank, Nanjing, Jiangsu, China.
authors.forename: Zhicong
authors.initials: Z
authors.lastname: Liao
authors.affiliation: Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University and Nanjing Multi-Center Biobank, Nanjing, Jiangsu, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Yeting
authors.initials: Y
authors.lastname: Hong
authors.affiliation: 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.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Baoliang
authors.initials: B
authors.lastname: Guo
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
authors.affiliation: 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.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University and Nanjing Multi-Center Biobank, Nanjing, Jiangsu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Qipeng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C400134:BAP1 protein, human; D014408:Biomarkers, Tumor; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
keywords: BAP1; apoptosis; lung cancer; miR-31; proliferation