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

Min Xie1, Ming Sun1, Ya-nan Zhu1

  • 1Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.

Oncotarget
|September 19, 2015
PubMed

Insights

HOXA-AS2, a long noncoding RNA (lncRNA), is upregulated in gastric cancer (GC) and promotes tumor growth. It acts as an oncogene by epigenetically silencing tumor suppressor genes, suggesting its potential as a GC biomarker and therapeutic target.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • Long noncoding RNAs (lncRNAs) are increasingly recognized as critical regulators in human cancer development.
  • Gastric cancer (GC) pathogenesis involves complex molecular alterations, including the dysregulation of lncRNAs.

Purpose of the Study:

  • To investigate the role of HOXA cluster antisense RNA2 (HOXA-AS2) in gastric cancer.
  • To elucidate the molecular mechanisms underlying HOXA-AS2's function in GC progression.

Main Methods:

  • Quantitative real-time PCR to assess HOXA-AS2 expression levels in GC tissues and cell lines.
  • Cell proliferation assays, cell cycle analysis, and apoptosis assays to evaluate the functional impact of HOXA-AS2.
  • Chromatin immunoprecipitation (ChIP) assays and Western blotting to investigate the interaction between HOXA-AS2, EZH2, and target gene promoters.

Main Results:

  • HOXA-AS2 expression was significantly upregulated in GC tissues and correlated with advanced tumor size, higher clinical stage, and poorer patient prognosis.
  • HOXA-AS2 knockdown inhibited GC cell proliferation by inducing G1 arrest and apoptosis, while its overexpression promoted cell growth.
  • HOXA-AS2 epigenetically repressed the expression of P21, PLK3, and DDIT3 by recruiting EZH2 to their promoter regions, leading to H3K27 trimethylation.

Conclusions:

  • HOXA-AS2 functions as an oncogene in gastric cancer, partly by suppressing the expression of P21, PLK3, and DDIT3.
  • HOXA-AS2 represents a potential prognostic biomarker and a promising therapeutic target for gastric cancer.
Keywords:
HOXA-AS2P21/PLK3/DDIT3PRC2gastric cancerproliferation

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