Xie Juan, Wang Jing-Jing, Li Ya-Jun, Wu Jia, Gu Xiao-Jing, Yang Xiao-Rong
Department of Gastroenterology, General Hospital of Ningxia Medical University, Ningxia 750004, Yinchuan, China.
Evid Based Complement Alternat Med. 2022 Aug 24;2022:3298939. doi: 10.1155/2022/3298939. eCollection 2022.
GAS5 is abnormally high in colorectal cancer tissues, which is a specific expression of lncRNA in colorectal cancer (CRC). Nevertheless, its biological function in CRC has not been elucidated. The abnormal high expression of GAS5 in CRC is the specific expression of lncRNA in CRC. The purpose of our study is to explore the effect of GAS5 on CRC and its mechanism. The expression of GAS5 in 53 paired normal and colorectal cancer tissues and colorectal cancer cell lines was detected by real-time PCR. The biological effects of GAS5, miR-21, and LIFR were measured by functional assays, including wound healing, transwell assays, and in vivo assays. We ensured the carcinogenesis role of GAS5 in CRC in the xenograft nude model. The dual-luciferase reporter assay system and chromatin immunoprecipitation method were used for target evaluation and Western blot for verification. GAS5 was significantly decreased in tumor tissues and CRC cells, and the low expression of CAS5 in CRC promoted tumor metastasis and decreased the survival of patients. GAS5 knockdown increases the cell viability, inhibits apoptosis, and promotes migration. Xenografted tumors in nude mice studies showed that GAS5 knockdown promoted tumor growth and caused worse lesions in colorectal. Furthermore, GAS5 increases the expression level of target gene LIFR to promote the apoptosis of CRC cells by binding to miR-21. Our study revealed that a novel pathway about lncRNA GAS5 inhibited the proliferation and metastasis of CRC cells by targeting miR-21/LIFR which provides a new strategy to treat CRC.
GAS5在结直肠癌组织中异常高表达，这是lncRNA在结直肠癌（CRC）中的一种特异性表达。然而，其在CRC中的生物学功能尚未阐明。GAS5在CRC中的异常高表达是lncRNA在CRC中的特异性表达。我们研究的目的是探讨GAS5对CRC的影响及其机制。通过实时PCR检测53对正常和结直肠癌组织及结直肠癌细胞系中GAS5的表达。通过功能实验，包括伤口愈合实验、transwell实验和体内实验，来检测GAS5、miR-21和LIFR的生物学效应。我们在异种移植裸鼠模型中确定了GAS5在CRC中的致癌作用。采用双荧光素酶报告基因检测系统和染色质免疫沉淀法进行靶点评估，并用蛋白质免疫印迹法进行验证。GAS5在肿瘤组织和CRC细胞中显著降低，CRC中CAS5的低表达促进肿瘤转移并降低患者生存率。敲低GAS5可增加细胞活力、抑制细胞凋亡并促进细胞迁移。裸鼠异种移植瘤研究表明，敲低GAS5可促进肿瘤生长并导致结直肠病变更严重。此外，GAS5通过与miR-21结合增加靶基因LIFR的表达水平，从而促进CRC细胞凋亡。我们的研究揭示了一条关于lncRNA GAS5通过靶向miR-21/LIFR抑制CRC细胞增殖和转移的新途径，这为治疗CRC提供了一种新策略。
