Li Ping, Wang Liuhua, Li Pengfei, Hu Fangyong, Cao Yi, Tang Dong, Ye Gang, Li Hongbo, Wang Daorong
Department of Central Laboratory, Huaian Tumor Hospital & Huaian Hospital of Huaian City, Huaian, 223200, PR China.
Department of General Surgery, Huaian Tumor Hospital & Huaian Hospital of Huaian City, Huaian, 223200, PR China.
Cancer Gene Ther. 2021 Apr;28(3-4):307-320. doi: 10.1038/s41417-020-00220-5. Epub 2020 Nov 16.
Gastric cancer (GC) is a common cancer and a leading cause of cancer-related deaths worldwide. Recent studies have supported the important role of long non-coding RNAs (lncRNAs) in GC progression. This study identified functional significance of X inactive specific transcript (XIST) in GC. The expression of XIST and EPHA1 in GC tissues and cells was measured. Then, dual luciferase reporter gene assay, RNA immunoprecipitation (RIP) assay and Chromatin Immunoprecipitation (ChIP) assay were performed to explore the interaction among XIST, EPHA1 and HNF4A. The effects of XIST on GG progression were evaluated by determining expression of proliferation- and invasion-related proteins (Ki67, PCNA, MMP-2, and MMP-9). Further, the functional role of XIST in GC with the involvement of NFκB pathway was also analyzed. Subsequently, the tumor growth in nude mice was evaluated. High expression of XIST and EPHA1 was observed in GC. XIST elevated EPHA1 expression by recruiting HNF4A. In addition, silencing of XIST inhibited GC progression in vitro and in vivo. Overexpressed XIST and EPHA1 yielded a reversed effect on cell proliferation and invasion. SN50 treatment (inhibitor of NFκB pathway) counteracted the promotive effect on GC cell proliferation and invasion mediated by XIST. The present study unveils that XIST increases the enrichment of HNF4A in the promoter region of EPHA1, thus promoting the deterioration of GC.
胃癌（GC）是一种常见癌症，也是全球癌症相关死亡的主要原因。最近的研究支持了长链非编码RNA（lncRNAs）在胃癌进展中的重要作用。本研究确定了X染色体失活特异性转录本（XIST）在胃癌中的功能意义。检测了XIST和EPH A1在胃癌组织和细胞中的表达。然后，进行双荧光素酶报告基因检测、RNA免疫沉淀（RIP）检测和染色质免疫沉淀（ChIP）检测，以探讨XIST、EPH A1和肝细胞核因子4A（HNF4A）之间的相互作用。通过检测增殖和侵袭相关蛋白（Ki67、增殖细胞核抗原（PCNA）、基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9））的表达来评估XIST对胃癌进展的影响。此外，还分析了XIST在涉及核因子κB（NFκB）通路的胃癌中的功能作用。随后，评估了裸鼠体内的肿瘤生长情况。在胃癌中观察到XIST和EPH A1的高表达。XIST通过招募HNF4A提高EPH A1的表达。此外，沉默XIST在体外和体内均抑制胃癌进展。过表达XIST和EPH A1对细胞增殖和侵袭产生相反的作用。SN50处理（NFκB通路抑制剂）抵消了XIST介导的对胃癌细胞增殖和侵袭的促进作用。本研究揭示，XIST增加了HNF4A在EPH A1启动子区域的富集，从而促进胃癌的恶化。
