Long noncoding RNA RP11-757G1.5 sponges miR-139-5p and upregulates YAP1 thereby promoting the proliferation and liver, spleen metastasis of colorectal cancer

Journal of Experimental & Clinical Cancer Research

Qilin Luo¹  Zhengming Zhu²  Jun Huang²  Jinfeng Zhu³  Chen Luo³  Fanqin Bu³  Kang Lin³  Ting Tan⁴  Xiaojian Zhu⁵ 

[1] Department of General Surgery, The Second Affiliated Hospital of Nanchang University, 330006, Nanchang, China;Department of General Surgery, The Second Affiliated Hospital of Nanchang University, 330006, Nanchang, China;Jiangxi Medical College of Nanchang University, Nanchang, China;Department of General Surgery, The Second Affiliated Hospital of Nanchang University, 330006, Nanchang, China;Jiangxi Medical College of Nanchang University, Nanchang, China;Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China;Department of General Surgery, The Second Affiliated Hospital of Nanchang University, 330006, Nanchang, China;Jiangxi Medical College of Nanchang University, Nanchang, China;Otolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China;The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China;Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China;

关键词: RP11-757G1.5;    LncRNAs;    miR-139-5p;    Proliferation;    ceRNA;    Colorectal cancer metastasis;   

DOI  :  10.1186/s13046-020-01717-5

来源: Springer

【 摘 要 】

BackgroundAccumulating evidence indicates that long non-coding RNAs (lncRNAs) acting as crucial regulators in tumorigenesis. However, its biological functions of lncRNAs in colorectal cancer (CRC) have not been systematically clarified.MethodsAn unbiased screening was performed to identify disregulated lncRNAs revealed to be implicated in CRC carcinogenesis according to an online-available data dataset. In situ hybridization (ISH), RT-qPCR and RNA fluorescence in situ hybridization (RNA-FISH) were applied to detect RP11-757G1.5 expression in CRC tissues and cell lines. The associations of RP11-757G1.5 with clinicopathological characteristics were analyzed. Their effects on prognosis were analyzed by the Kaplan-Meier analysis, Log-rank test, Univariate and Multivariate Cox regression analysis. The potential biological function of RP11-757G1.5 in CRC was investigated by Colony formation, Edu cell proliferation, Flow cytometry, Wound healing and Transwell assays. Bioinformatics binding site analysis, Luciferase reporter assay, Ago2 immunoprecipitation assays, RNA pull-down assay, RT-qPCR and Western blotting were utilized to demonstrate the mechanism of RP11-757G1.5 acts as a molecular sponge of miR-139-5p to regulate the expression of YAP1. Finally, we further explore the potential role of RP11-757G1.5 in CRC orthotopic xenografts in vivo.ResultsWe discovered a novel oncogenic lncRNA RP11-757G1.5, that was overexpressed in CRC tissues, especially in aggressive cases. Moreover, up-regulation of RP11-757G1.5 strongly correlated with poor clinical outcomes of patients with CRC. Functional analyses revealed that RP11-757G1.5 promoted cell proliferation in vitro and in vivo. Furthermore, RP11-757G1.5 stimulated cell migration and invasion in vitro and in vivo. Mechanistic studies illustrated that RP11-757G1.5 regulated the expression of YAP1 through sponging miR-139-5p and inhibiting its activity thereby promoting CRC progression and development.ConclusionsAltogether, these results reveal a novel RP11-757G1.5/miR-139-5p/YAP1 regulatory axis that participates in CRC carcinogenesis and progression.

【 授权许可】

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