Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong, China.
Department of Infectious Disease, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong, China.
Aging (Albany NY). 2022 Jan 6;14(1):368-388. doi: 10.18632/aging.203813.
Hepatocellular carcinoma (HCC) is one of the most death-related cancers worldwide. Identifying cancer-associated genes and uncovering the vital molecular mechanisms of HCC progression contribute greatly to the prognosis and novel therapeutic strategies for HCC patients. Although lncRNAs have been proved to be critical modulators of various cellular processes, the functions of lncRNAs in HCC progression are just emerging. Here, we found that a long non-coding RNA (lncRNA) named , whose biological effects have yet been unveiled in cancers, was associated with a better prognosis in patients with HCC. Gain-of-function analyses showed that inhibited the survival, migration, invasion and epithelial-to-mesenchymal transition (EMT) of HCC cells. Moreover, was enriched as a target of , which functioned as a sponge to regulate the endogenous levels of . Furthermore, we confirmed that served as a downstream target gene which was negatively controlled by . Importantly, a series of rescue experiments indicated that the tumor-suppressive effects of were achieved through the modulation of the / axis. In summary, we identified as a candidate tumor-inhibitory lncRNA that might serve as a biomarker for the prognosis of HCC and a promising therapeutic agent for patients with HCC.
肝细胞癌(HCC)是全球致死相关癌症之一。鉴定癌症相关基因和揭示 HCC 进展的重要分子机制,对 HCC 患者的预后和新的治疗策略有重大贡献。尽管 lncRNA 已被证明是各种细胞过程的关键调节剂,但 lncRNA 在 HCC 进展中的功能才刚刚开始显现。在这里,我们发现了一个长非编码 RNA(lncRNA),名为 ,其在癌症中的生物学作用尚未被揭示,与 HCC 患者的更好预后相关。功能获得分析表明, 抑制 HCC 细胞的存活、迁移、侵袭和上皮间质转化(EMT)。此外, 被富集为 的靶标,后者作为海绵调节 的内源性水平。此外,我们证实 作为一个下游靶基因,受 负调控。重要的是,一系列挽救实验表明, 通过调节 / 轴实现了 的肿瘤抑制作用。总之,我们将 鉴定为候选肿瘤抑制性 lncRNA,它可能作为 HCC 预后的生物标志物和 HCC 患者有前途的治疗剂。