Long non-coding RNA H19 promotes colorectal cancer metastasis via binding to hnRNPA2B1

Journal of Experimental & Clinical Cancer Research

Jing Wu¹  Changhua Zhang¹  Jin Li¹  Zhewei Wei²  Yuhui Zhang²  Jie Yu²  Yujie Yuan²  Weibin Huang²  Yulong He³ 

[1] Center for Digestive Disease, the Seventh Affiliated Hospital of Sun Yat-sen University, 628 Zhenyuan Road, 518000, Shenzhen, Guangdong, China;Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, 510080, Guangzhou, Guangdong, China;Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, 510080, Guangzhou, Guangdong, China;Center for Digestive Disease, the Seventh Affiliated Hospital of Sun Yat-sen University, 628 Zhenyuan Road, 518000, Shenzhen, Guangdong, China;

关键词: Colorectal cancer;    Metastasis;    H19;    hnRNPA2B1;    EMT;   

DOI  :  10.1186/s13046-020-01619-6

来源: Springer

【 摘 要 】

BackgroundLong non-coding RNA H19 was demonstrated to be significantly correlated with tumor metastasis. However, the specific functions of H19 in colorectal cancer (CRC) metastasis and the underlying mechanism are still largely unclear.MethodsUse public database to screen the potential lncRNA crucial for metastasis in colorectal cancer. The expression of H19 in clinical CRC specimens was detected by qRT-PCR. The effect of H19 on the metastasis of CRC cells was investigated by transwell, wound healing assays, CCK-8 assays and animal studies. The potential proteins binding to H19 were identified by LC-MS and verified by RNA immunoprecipitation (RIP). The expression of indicated RNA and proteins were measured by qRT-PCR or western blot.ResultsWe found the expression of lncRNA H19 was significantly upregulated in primary tumor and metastatic tissues, correlated with poor prognosis in CRC. Ectopic H19 expression promoted the metastasis of colorectal cancer cells in vitro and in vivo, and induced epithelial-to-mesenchymal transition (EMT). Mechanistically, H19 directly bound to hnRNPA2B1. Knockdown of hnRNPA2B1 attenuated the H19-induce migration and invasion in CRC cells. Furthermore, H19 stabilized and upregulated the expression of Raf-1 by facilitated the interaction between hnRNPA2B1 and Raf-1 mRNA, resulting in activation of Raf-ERK signaling.ConclusionsOur findings demonstrate the role of H19/hnRNPA2B1/EMT axis in regulation CRC metastasis, suggested H19 could be a potential biomarker to predict prognosis as well as a therapeutic strategy for CRC.

【 授权许可】

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