Antisense Long Noncoding RNA HIF1A-AS2 Is Upregulated in Gastric Cancer and Associated with Poor Prognosis

Dig Dis Sci. 2015 Jun;60(6):1655-62. doi: 10.1007/s10620-015-3524-0. Epub 2015 Feb 17.


Background: Long noncoding RNAs (lncRNAs) have been recently shown to play important regulatory roles in fundamental biological processes, and many of them are deregulated in several human cancers. LncRNA hypoxia-inducible factor 1alpha antisense RNA-2 (HIF1A-AS2) is overexpressed in nonpapillary clear-cell renal carcinomas and involved in cancer progression.

Aim: This study was to evaluate the expression of HIF1A-AS2 in gastric cancer (GC) and further explore its biological function in GC cells.

Materials and methods: Quantitative real-time polymerase chain reaction was used to detect the expression level of HIF1A-AS2 in GC tissues. The correlation of its expression with clinicopathological features was analyzed. Area under receiver operating characteristic curve (ROC(AUC)) was constructed to evaluate the diagnostic value of HIF1A-AS2. Besides, tumor cell proliferation was assessed following knockdown of HIF1A-AS2, by MTT and colony formation assay in vitro, and tumor formation assay in a nude mouse model in vivo.

Results: The expression of HIF1A-AS2 was upregulated in GC tumorous tissues compared with the adjacent normal tissues (P < 0.001). Its overexpression was correlated with TNM stages (P = 0.008), tumor invasion (P = 0.016), lymph node metastasis (P = 0.042), and poor prognosis (P = 0.001). In addition, ROC(AUC) of HIF1A-AS2 was up to 0.673 (95 % CI 0.596-0.744, P < 0.001). Moreover, knockdown of HIF1A-AS2 expression by siRNA could inhibit cell proliferation in vitro and tumorigenesis in vivo.

Conclusions: HIF1A-AS2 is overexpressed in GC and may play a pivotal role in tumor cell proliferation. It can be used as a potential diagnostic and prognostic biomarker for GC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Prognosis
  • RNA / isolation & purification
  • RNA, Antisense / metabolism*
  • RNA, Long Noncoding / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • Survival Rate
  • Transfection
  • Up-Regulation


  • Biomarkers, Tumor
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Antisense
  • RNA, Long Noncoding
  • long noncoding RNA HIF1A-AS2, human
  • RNA