Chen Wen-Ming, Huang Ming-de, Kong Rong, Xu Tong-Peng, Zhang Er-Bao, Xia Rui, Sun Ming, De Wei, Shu Yong-Qian
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, Jiangsu Province, China,
Dig Dis Sci. 2015 Jun;60(6):1655-62. doi: 10.1007/s10620-015-3524-0. Epub 2015 Feb 17.
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.
This study was to evaluate the expression of HIF1A-AS2 in gastric cancer (GC) and further explore its biological function in GC cells.
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.
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.
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.
长链非编码RNA（lncRNAs）最近被证明在基本生物学过程中发挥重要调节作用，并且其中许多在几种人类癌症中表达失调。长链非编码RNA缺氧诱导因子1α反义RNA-2（HIF1A-AS2）在非乳头状透明细胞肾癌中过表达，并参与癌症进展。
本研究旨在评估HIF1A-AS2在胃癌（GC）中的表达，并进一步探讨其在GC细胞中的生物学功能。
采用定量实时聚合酶链反应检测GC组织中HIF1A-AS2的表达水平。分析其表达与临床病理特征的相关性。构建受试者操作特征曲线下面积（ROC（AUC））以评估HIF1A-AS2的诊断价值。此外，在敲低HIF1A-AS2后，通过体外MTT和集落形成试验以及体内裸鼠模型中的肿瘤形成试验评估肿瘤细胞增殖。
与相邻正常组织相比，GC肿瘤组织中HIF1A-AS2的表达上调（P < 0.001）。其过表达与TNM分期（P = 0.008）、肿瘤侵袭（P = 0.016）、淋巴结转移（P = 0.042）和预后不良（P = 0.001）相关。此外，HIF1A-AS2的ROC（AUC）高达0.673（95%CI 0.596 - 0.744，P < 0.001）。此外，通过siRNA敲低HIF1A-AS2表达可抑制体外细胞增殖和体内肿瘤发生。
HIF1A-AS2在GC中过表达，可能在肿瘤细胞增殖中起关键作用。它可作为GC的潜在诊断和预后生物标志物。
