Long non-coding RNA H19 promotes colorectal cancer metastasis via binding to hnRNPA2B1
Authors: Jie Yu
Jing Wu
Yujie Yuan
Jin Li
Yulong He
Weibin Huang
Changhua Zhang
Yuhui Zhang
Zhewei Wei
Journal: Journal of Experimental & Clinical Cancer Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: Colorectal cancer; EMT; H19; Metastasis; hnRNPA2B1.
Affiliations: Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China., Center for Digestive Disease, the Seventh Affiliated Hospital of Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, 518000, Guangdong, China., Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China. ., Center for Digestive Disease, the Seventh Affiliated Hospital of Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, 518000, Guangdong, China. .

Abstract:  Background: Long 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. Methods: Use 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. Results: We 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. Conclusions: Our 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. 

Retracted: No

PubPeer comments:
 Two images in Figure 2d appear to overlap, after rotation. This type of issue is sometimes seen in papers that have been outsourced. *** ![file] *** Funding. This study was supported by Science and Technology Project of Guangzhou (No. 201803040019), National Natural Science Foundation of China (No. 81702325) and Natural Science Foundation of Guangdong Province (No. 2017A030310565 and 2016A020213002). , 
 Two images in Figure 5 appear to be the same, but are described differently. *** ![file] , 
 #1 This issue was corrected in March 2021. Following publication of the original article [1], the authors identified minor errors in image-typesetting in Fig. 2; specifically the migration transwell assay of sh-H19u20132 DLD1 cells group displayed in Fig. 2d. ![file] , 
 Dear Actinopolyspora, Thanks very much for your valuable comments on our published manuscript. We have checked the raw data carefully and found that these two duplicated pictures were misplaced during the picture assembling. According to the raw data, the picture of trnaswell assay in Figure 5e was right, while the picture in Figure 5b was mistakenly used. The picture after correction is showed below. Sincerely apologized for our carelessness to neglect this mistake in the correction one year ago. This correction won t influence the interpretation of the results and conclusions in this manuscript. We will contact the editorial office. Sorry for our mistakes in this matter. Best wished Yuhui Zhang ![file] ,