Lian Yifan, Li Zhaohua, Fan Yanyun, Huang Qingwen, Chen Jianmin, Liu Wenming, Xiao Chuanxing, Xu Hongzhi
Department of Gastroenterology, Zhongshan Hospital, Xiamen UniversityXiamen, People's Republic of China.
Institute for Microbial Ecology, Xiamen UniversityXiamen, People's Republic of China.
Am J Transl Res. 2017 Dec 15;9(12):5496-5506. eCollection 2017.
Emerging evidence have indicated that long non-coding RNAs (lncRNAs) play crucial roles in cancer development and progression. Previous studies have suggested that lncRNA-HOXA cluster antisense RNA 2 (HOXA-AS2) is involved in tumorigenesis of several cancers. However, little is known about the alteration and biological functions of HOXA-AS2 in pancreatic cancer (PC). The purpose of this study is to identify the role of HOXA-AS2 in PC. Here, we provided evidence that lncRNA HOXA-AS2 was up-regulated in PC tissues. In addition, Loss-of-function experiments revealed that HOXA-AS2 knockdown effectively suppressed proliferation by blocking the cell cycle transition and caused apoptosis of PC cells in vitro and in vivo. Mechanistically, we found that HOXA-AS2 directly interacted with enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1), which promoted PC cell growth ability. Collectively, our findings demonstrated that lncRNA-HOXA-AS2/EZH2/LSD1 complex may function as an oncogene in PC cell proliferation, and also provides a potential therapy target for PC.
新出现的证据表明,长链非编码RNA(lncRNA)在癌症的发生和发展中起着关键作用。先前的研究表明,lncRNA-HOXA簇反义RNA 2(HOXA-AS2)参与了多种癌症的肿瘤发生过程。然而,关于HOXA-AS2在胰腺癌(PC)中的改变及其生物学功能知之甚少。本研究的目的是确定HOXA-AS2在PC中的作用。在此,我们提供证据表明lncRNA HOXA-AS2在PC组织中上调。此外,功能丧失实验表明,敲低HOXA-AS2可通过阻断细胞周期转换有效抑制增殖,并在体外和体内诱导PC细胞凋亡。机制上,我们发现HOXA-AS2直接与zeste同源物2(EZH2)增强子和赖氨酸特异性去甲基化酶1(LSD1)相互作用,从而促进PC细胞的生长能力。总的来说,我们的研究结果表明lncRNA-HOXA-AS2/EZH2/LSD1复合物可能作为一种癌基因在PC细胞增殖中发挥作用,也为PC提供了一个潜在的治疗靶点。