Oncotarget

Research Papers:

Long noncoding RNA HOXA-AS2 promotes gastric cancer proliferation by epigenetically silencing P21/PLK3/DDIT3 expression

Min Xie, Ming Sun, Ya-nan Zhu, Rui Xia, Yan-wen Liu, Jie Ding, Hong-wei Ma, Xue-zhi He, Zhi-hong Zhang, Zhi-jun Liu, Xiang-hua Liu and Wei De _

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Oncotarget. 2015; 6:33587-33601. https://doi.org/10.18632/oncotarget.5599

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Abstract

Min Xie1,*, Ming Sun1,*, Ya-nan Zhu1,*, Rui Xia1, Yan-wen Liu1, Jie Ding2, Hong-wei Ma3, Xue-zhi He1, Zhi-hong Zhang3, Zhi-jun Liu1, Xiang-hua Liu1 and Wei De1

1 Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People’s Republic of China

2 Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China

3 Department of Pathology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China

* These authors have contributed equally to this work

Correspondence to:

Wei De, email:

Keywords: gastric cancer; HOXA-AS2; proliferation; PRC2; P21/PLK3/DDIT3

Received: March 10, 2015 Accepted: August 26, 2015 Published: September 10, 2015

Abstract

Current evidence suggests that long noncoding RNAs (lncRNAs) may be an important class of functional regulators involved in human cancers development, including gastric cancer (GC). Here, we reported that HOXA cluster antisense RNA2 (HOXA-AS2), a 1048bp RNA, was upregulated in GC. Increased HOXA-AS2 expression in GC was associated with larger tumor size and higher clinical stage; patients with higher levels of HOXA-AS2 expression had a relatively poor prognosis. Further experiments revealed that HOXA-AS2 knockdown significantly inhibited GC cells proliferation by causing G1 arrest and promoting apoptosis, whereas HOXA-AS2 overexpression promoted cell growth. Furthermore, HOXA-AS2 could epigenetically repress the expression of P21, PLK3, and DDIT3 via binding with EZH2 (enhaner of zeste homolog 2), a key component of PRC2; ChIP assays demonstrated that EZH2 could directly bind to the promoter of P21, PLK3 and DDIT3, inducing H3K27 trimethylated. In conclusion, these data suggest that HOXA-AS2 could be an oncogene for GC partly through suppressing P21, PLK3, and DDIT3 expression; HOXA-AS2 may be served as a candidate prognostic biomarker and target for new therapies in human GC.


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