Zhu Xiaojian, Zhu Jinfeng, Tan Ting, Bu Fanqin, Zhao Jiefeng, Luo Chen, Luo Hongliang
Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Jiangxi Medical College of Nanchang University, Nanchang, China.
Carcinogenesis. 2021 Jul 16;42(7):984-994. doi: 10.1093/carcin/bgab044.
Long non-coding RNAs (lncRNAs) have been characterized by playing a crucial role in tumorigenesis. However, the detail biological function and clinical importance of lncRNAs in colorectal cancer (CRC) are unclear and have attracted different levels of in-depth research. In this context, we explored the differentially expressed profiles of lncRNAs in six CRC tissues and three adjacent non-tumor tissues from RNA-sequencing (RNA-seq) study and noted a lncRNA, RP11-51O6.1, which is markedly overexpressed in CRC tissues, particularly in aggressive cases. Impressively, an elevated RP11-51O6.1 level was highly correlated with poor prognosis in clinical patients. Functional analyses revealed that RP11-51O6.1 could promote cell proliferation in vitro and in vivo. Furthermore, we reported that RP11-51O6.1 enhances cell migration and invasion in vitro. Mechanistic studies (Bioinformatics binding site analyses, the Luciferase reporter, Ago2 immunoprecipitation, the RNA pull-down, immunofluorescence colocalization, rescued assays and western blotting) implicated that RP11-51O6.1 could regulate YAP1 expression by competitively sponging miR-206 and blocking its activity in promoting CRC progression. Conclusively, our findings identify a novel RP11-51O6.1/miR-206/YAP1 regulatory axis that participates in CRC progression and development, suggesting RP11-51O6.1 is an exploitable biomarker and appealing therapeutic target in treating CRC.
长链非编码RNA（lncRNAs）在肿瘤发生过程中发挥着关键作用。然而，lncRNAs在结直肠癌（CRC）中的具体生物学功能和临床重要性尚不清楚，已引起不同层面的深入研究。在此背景下，我们通过RNA测序（RNA-seq）研究，探索了6例CRC组织和3例相邻非肿瘤组织中lncRNAs的差异表达谱，发现了一种lncRNA，即RP11-51O6.1，其在CRC组织中显著过表达，尤其是在侵袭性病例中。令人印象深刻的是，临床患者中RP11-51O6.1水平升高与预后不良高度相关。功能分析表明，RP11-51O6.1在体外和体内均可促进细胞增殖。此外，我们报道RP11-51O6.1在体外可增强细胞迁移和侵袭。机制研究（生物信息学结合位点分析、荧光素酶报告基因检测、AGO2免疫沉淀、RNA下拉实验、免疫荧光共定位、挽救实验和蛋白质印迹法）表明，RP11-51O6.1可通过竞争性结合miR-206并阻断其促进CRC进展的活性来调节YAP1表达。总之，我们的研究结果确定了一种新的RP11-51O6.1/miR-206/YAP1调控轴，其参与CRC的进展和发展，提示RP11-51O6.1是一种可开发的生物标志物，也是治疗CRC的有吸引力的治疗靶点。
