Research Papers:

MicroRNA-3196 is inhibited by H2AX phosphorylation and attenuates lung cancer cell apoptosis by downregulating PUMA

Chengshan Xu, Ling Zhang, Lianning Duan and Chengrong Lu _

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Oncotarget. 2016; 7:77764-77776. https://doi.org/10.18632/oncotarget.12794

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Chengshan Xu1,2, Ling Zhang1, Lianning Duan1, Chengrong Lu1

1Aviation Medicine Research Laboratory, Air Force General Hospital, PLA, Beijing 100142, China

2Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China

Correspondence to:

Chengrong Lu, email: [email protected]

Keywords: lung cancer, histone H2AX, miR-3196, PUMA, apoptosis

Received: June 01, 2016     Accepted: October 14, 2016     Published: October 21, 2016


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.

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