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.
Highlights
Gastric cancer (GC) is the fourth most commonly diagnosed cancer and the second leading cause of cancer death [1]
We analyzed the expression levels of HOXA-AS2 in human GC tissues by using raw microarray data downloaded from Gene Expression Omnibus (GEO) (GSE50710) [9], and found that HOXA-AS2 expression levels were upregulated in gastric cancerous tissues compared with noncancerous www.impactjournals.com/oncotarget tissues (Figure 1A)
More evidence have emerged that dysregulation of many long noncoding RNAs (lncRNAs) in GC could be considered as one of the leading forces during GC tumorigenesis, as exemplified by GAS5 in our previous study [27]
Summary
Gastric cancer (GC) is the fourth most commonly diagnosed cancer and the second leading cause of cancer death [1]. Better understanding of the mechanism of gastric carcinogenesis is essential for GC diagnosis and therapy. With the advance of high-resolution microarray and massively parallel sequencing technology, it has been gradually verified that only 2% of the genome sequences encode proteins, while the remainder is transcribed into noncoding RNAs (ncRNAs) [4, 5]. According to their size, ncRNAs can be extensively divided into two groups: short ncRNAs (200nt) [6]. Aberrant expressions of lncRNAs may potentially alter basic cellular biological processes and contribute to tumorigenesis [8]. A plenty of evidence have demonstrated that lncRNAs act www.impactjournals.com/oncotarget
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