Journal
ONCOTARGET
Volume 7, Issue 12, Pages 13742-13753Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.7328
Keywords
lung cancer; BAP1; miR-31; proliferation; apoptosis
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Funding
- National Basic Research Program of China (973 Program) [2014CB542300]
- National Natural Science Foundation of China [81250044, 81101330, 31271378, 81401895, 81372838]
- Research Special Fund for Public Welfare Industry of Health [201302018]
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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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