Cui Yan, Yi Lei, Zhao Ji-Zong, Jiang Yu-Gang
1 Department of Neurosurgery, The Second Xiangya Hospital of Central South University , Chang Sha, China .
2 Department of Neurosurgery, Tiantan Hospital, Capital Medical University , Beijing, China .
DNA Cell Biol. 2017 Oct;36(10):822-828. doi: 10.1089/dna.2017.3805. Epub 2017 Aug 23.
Long noncoding RNAs (lncRNAs) have been proved as important regulators in many diseases, including cancers. HOXA11 antisense 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 upregulated in glioma tissue and cell lines compared with the adjacent normal tissue and cells. Moreover, patients with high HOXA11-AS expression had a shorter survival 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. Taken together, the 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高表达患者的生存期短于低表达患者,预后较差。功能丧失实验表明,敲低HOXA11-AS可抑制增殖,诱导细胞周期停滞于G0/G1期,并增强细胞凋亡。生物信息学预测表明,miR-140-5p在3'-UTR直接靶向HOXA11-AS,荧光素酶报告基因实验证实了这一点。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、细胞周期停滞和细胞凋亡的作用。综上所述,本研究表明HOXA11-AS sponge miR-140-5p通路可能在胶质瘤的发生发展中起重要调控作用。