title: Long noncoding RNA HOXA-AS2 promotes gastric cancer proliferation by epigenetically silencing P21/PLK3/DDIT3 expression.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Ya-nan
authors.initials: YN
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xia
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Yan-wen
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Pathology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Hong-wei
authors.initials: HW
authors.lastname: Ma
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Xue-zhi
authors.initials: XZ
authors.lastname: He
authors.affiliation: Department of Pathology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Zhi-hong
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Zhi-jun
authors.initials: ZJ
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Xiang-hua
authors.initials: XH
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: De
mesh_terms: D000368:Aged; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis* / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051742:Transcription Factor CHOP / Q000096:biosynthesis* / Q000235:genetics; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation; D000097868:Polo-like Kinases
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D017346:Protein Serine-Threonine Kinases; D062085:RNA, Long Noncoding; D051742:Transcription Factor CHOP; D025521:Tumor Suppressor Proteins; C493956:CDKN1A protein, human; C497249:DDIT3 protein, human; C486256:PLK3 protein, human; D000097868:Polo-like Kinases
keywords: HOXA-AS2; P21/PLK3/DDIT3; PRC2; gastric cancer; proliferation