Cui Yan, Yi Lei, Zhang Ming-Ming, Zhou Yu, Tan Zhi-Gang, Huang Tao, Jiang Yu-Gang
Department of Neurosurgery, the Second Xiangya Hospital of Central South University, Renmin Road, Chang Sha, Hunan Province,410011, China.
Oncol Res. 2017 Jun 12. doi: 10.3727/096504017X14972669062547.
Long non-coding RNAs (lncRNAs) are proved as important regulators in many diseases, including multiple cancers. HOXA11antisense RNA (HOXA11-AS) is a novel identified lncRNA associated with cancer progression. However, the role of HOXA11-AS in glioma remains poorly understood and needs to be elucidated. The purpose of this study is to investigate the role and regulating mechanism of HOXA11-AS on gliomagenesis. Expression of HOXA11-AS was significantly up-regulated in glioma tissue and cell lines compared to the adjacent normal tissue and cells. Moreover, patients with high HOXA11-AS expression had a shorter survival time and poorer prognosis than that of lower expression. Loss-of-function experiments revealed that HOXA11-AS knockdown inhibited the proliferation, induced cell cycle arrest at G0/G1 phase and enhanced the apoptosis. Bioinformatics prediction forecast that miR-140-5p directly targeted HOXA11-AS at 3'-UTR, which was confirmed by luciferase reporter assay. In vitro rescue experiment assays, miR-140-5p inhibitor transfection could reverse the function of HOXA11-AS knockdown on the proliferation, cell cycle arrest and apoptosis. Together, present study illustrates that the pathway of HOXA11-AS sponging miR-140-5p might play a vital regulating role in the development and progression of glioma.
长链非编码RNA（lncRNAs）已被证明是包括多种癌症在内的许多疾病中的重要调节因子。HOXA11反义RNA（HOXA11-AS）是一种新发现的与癌症进展相关的lncRNA。然而，HOXA11-AS在胶质瘤中的作用仍知之甚少，需要进一步阐明。本研究的目的是探讨HOXA11-AS在胶质瘤发生中的作用及其调控机制。与邻近正常组织和细胞相比，HOXA11-AS在胶质瘤组织和细胞系中的表达显著上调。此外，HOXA11-AS高表达的患者比低表达患者的生存时间更短，预后更差。功能丧失实验表明，敲低HOXA11-AS可抑制增殖，诱导细胞周期停滞在G0/G1期并增强凋亡。生物信息学预测表明miR-140-5p在3'-UTR直接靶向HOXA11-AS，荧光素酶报告基因检测证实了这一点。在体外挽救实验中，转染miR-140-5p抑制剂可逆转敲低HOXA11-AS对增殖、细胞周期停滞和凋亡的作用。总之，本研究表明HOXA11-AS海绵化miR-140-5p的途径可能在胶质瘤的发生和发展中起重要调节作用。
