title: MicroRNA-3196 is inhibited by H2AX phosphorylation and attenuates lung cancer cell apoptosis by downregulating PUMA.
abstract: Histone H2AX is a tumor suppressor protein that plays an important role in apoptosis. However, the mechanism underlying the association of H2AX with apoptosis in cancer cells remains elusive. Here, we showed that H2AX knockdown in lung cancer A549 cells affected the expression of 16 microRNAs (miRNAs), resulting in the downregulation of 1 and the upregulation of 15 miRNAs. MicroRNA-3196 (miR-3196) was identified as a target of H2AX and shown to inhibit apoptosis in lung cancer cells by targeting p53 upregulated modulator of apoptosis (PUMA). Phosphorylated H2AX (γH2AX) was shown to bind to the promoter of miR-3196 and regulate its expression. In addition, H2AX phosphorylation increased H3K27 trimethylation in the promoter region of miR-3196 and inhibited the binding of RNA polymerase II to the promoter of miR-3196, leading to the inhibition of miR-3196 transcription. Taken together, these results indicated that H2AX phosphorylation regulates apoptosis in lung cancer cells via the miR-3196/PUMA pathway.
authors: Aviation Medicine Research Laboratory, Air Force General Hospital, PLA, Beijing 100142, China.|Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Chengshan
authors: C
authors: Xu
authors: Aviation Medicine Research Laboratory, Air Force General Hospital, PLA, Beijing 100142, China.
authors: Ling
authors: L
authors: Zhang
authors: Aviation Medicine Research Laboratory, Air Force General Hospital, PLA, Beijing 100142, China.
authors: Lianning
authors: L
authors: Duan
authors: Aviation Medicine Research Laboratory, Air Force General Hospital, PLA, Beijing 100142, China.
authors: Chengrong
authors: C
authors: Lu
mesh_terms: D000072283:A549 Cells; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C468783:H2AX protein, human; D006657:Histones; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins
keywords: PUMA; apoptosis; histone H2AX; lung cancer; miR-3196