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

作者:Chen, Wen-ming; Huang, Ming-de; Kong, Rong; Xu, Tong-peng; Zhang, Er-bao; Xia, Rui; Sun, Ming; De, Wei; Shu, Yong-qian*
来源:Digestive Diseases and Sciences, 2015, 60(6): 1655-1662.
DOI:10.1007/s10620-015-3524-0

摘要

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 (ROCAUC) 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, ROCAUC 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.