Tian Qing, Yan Xiaodong, Yang Long, Liu Zirong, Yuan Zheyue, Shen Zhongyang, Zhang Yamin
Department of Hepatobiliary Surgery, Tianjin First Central Hospital Tianjin 300192, P. R. China.
Tianjin Key Laboratory for Transplantation, Tianjin First Central Hospital Tianjin 300192, P. R. China.
Am J Transl Res. 2020 May 15;12(5):2257-2266. eCollection 2020.
Non-coding RNA has been reported to be crucial regulator for cancer progression. This work was aimed to investigate the roles and associated mechanisms of non-coding RNA activated by DNA damage (NORAD) in hepatocellular carcinoma (HCC) progression. In this work, we explored the expression of NORAD, microRNA-144-3p (miR-144-3p), and septin 2 (SEPT2) in HCC tissues and cells. Effects of knockdown of ectopic of NORAD on HCC cell proliferation, colony formation, and apoptosis were explored. Rescue experiments were conducted to explore whether NORAD regulates HCC cell behaviors via the miR-144-3p/SEPT2 axis. Moreover, the effect of NORAD on HCC tumor progression was analyzed. We showed NORAD expression was elevated in both HCC tissues and cells. NORAD knockdown inhibits HCC cell growth but promotes apoptosis, while the overexpression of NORAD has opposite effects. Besides that, we found knockdown of NPRAD inhibits tumor growth. Moreover, we showed miR-144-3p expression was inversely correlated with NORAD and SEPT2, while NORAD and SEPT2 was positively correlated in HCC tissues. Functional assays showed NORAD functions as ceRNA through binding with miR-144-3p to regulate SEPT2 expression in HCC. Collectively, we showed NORAD serves as an oncogenic lncRNA to promote HCC progression via the miR-144-3p/SEPT2 axis.
据报道，非编码RNA是癌症进展的关键调节因子。这项工作旨在研究DNA损伤激活的非编码RNA（NORAD）在肝细胞癌（HCC）进展中的作用及相关机制。在这项研究中，我们探究了NORAD、微小RNA-144-3p（miR-144-3p）和septin 2（SEPT2）在HCC组织和细胞中的表达。探讨了敲低或异位表达NORAD对HCC细胞增殖、集落形成和凋亡的影响。进行了挽救实验以探究NORAD是否通过miR-144-3p/SEPT2轴调节HCC细胞行为。此外，分析了NORAD对HCC肿瘤进展的影响。我们发现NORAD在HCC组织和细胞中表达均升高。敲低NORAD可抑制HCC细胞生长但促进凋亡，而NORAD过表达则有相反作用。除此之外，我们发现敲低NORAD可抑制肿瘤生长。此外，我们发现miR-144-3p的表达与NORAD和SEPT2呈负相关，而在HCC组织中NORAD和SEPT2呈正相关。功能分析表明，NORAD作为竞争性内源RNA（ceRNA），通过与miR-144-3p结合来调节HCC中SEPT2的表达。总的来说，我们表明NORAD作为一种致癌长链非编码RNA，通过miR-144-3p/SEPT2轴促进HCC进展。
