Zhong Guang-Yu, Tan Jia-Nan, Huang Jing, Zhou Sheng-Ning, Yu Jin-Hao, Zhong Lin, Hou Dong, Zhi Shi-Lin, Zeng Jin-Tao, Li Hong-Ming, Zheng Chu-Lian, Yang Bin, Han Fang-Hai
Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510275, China.
Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu 610041, China.
Cancers (Basel). 2022 Oct 25;14(21):5237. doi: 10.3390/cancers14215237.
Many studies reported that long noncoding RNAs (lncRNAs) play a critical role in gastric cancer (GC) metastasis and tumorigenesis. However, the underlying mechanisms of lncRNAs in GC remain unexplored to a great extent. LINC01537 expression level was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Its biological roles in GC were then investigated using functional experiments. In order to investigate the underlying mechanism of LINC01537 in GC, RNA pull-down, RNA immunoprecipitation, and ubiquitination assays were performed. LINC01537 was significantly overexpressed in GC tissues and associated with a poor prognosis. Functional experimental results revealed that LINC01537 promoted the proliferation, invasion, and migration of GC cells. The animal experiments revealed that LINC01537 promoted tumorigenesis and metastasis in vivo. Mechanistically, LINC01537 stabilizes RIPK4 by reducing the binding of RIPK4 to TRIM25 and reducing its ubiquitination degradation, thereby promoting the expression of the NF-κB signaling pathway. According to our findings, the LINC01537-RIPK4-NF-κB axis promoted GC metastasis and tumorigenesis.
许多研究报道,长链非编码RNA(lncRNAs)在胃癌(GC)转移和肿瘤发生中起关键作用。然而,lncRNAs在GC中的潜在机制在很大程度上仍未被探索。使用定量逆转录-聚合酶链反应(qRT-PCR)和免疫组织化学(IHC)检测LINC01537的表达水平。然后通过功能实验研究其在GC中的生物学作用。为了研究LINC01537在GC中的潜在机制,进行了RNA下拉、RNA免疫沉淀和泛素化分析。LINC01537在GC组织中显著过表达,并与不良预后相关。功能实验结果表明,LINC01537促进了GC细胞的增殖、侵袭和迁移。动物实验表明,LINC01537在体内促进肿瘤发生和转移。机制上,LINC01537通过减少RIPK4与TRIM25的结合并降低其泛素化降解来稳定RIPK4,从而促进NF-κB信号通路的表达。根据我们的研究结果,LINC01537-RIPK4-NF-κB轴促进了GC转移和肿瘤发生。