Long non-coding RNA H19 promotes colorectal cancer metastasis via binding to hnRNPA2B1
Long non-coding RNA H19 promotes colorectal cancer metastasis via binding to hnRNPA2B1
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长非编码RNA H19通过结合hnRNPA2B1促进结直肠癌转移
DOI：
10.1186/s13046-020-01619-6
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发表时间：
2020-07-22
影响因子：
11.3
通讯作者：
Zhang, Changhua
中科院分区：
文献类型：
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作者：
Zhang, Yuhui;Huang, Weibin;Zhang, Changhua
研究背景长链非编码RNA H19与肿瘤转移密切相关。然而，H19在结直肠癌（colorectal cancer，CRC）转移中的具体功能及其机制尚不清楚。采用qRT-PCR方法检测H19在大肠癌临床标本中的表达。通过transwell、伤口愈合实验、CCK-8实验和动物实验研究H19对CRC细胞转移的影响。通过LC-MS鉴定与H19结合的潜在蛋白质，并通过RNA免疫沉淀（RIP）验证。结果发现lncRNA H19在大肠癌原发灶和转移灶中的表达均显著上调，与大肠癌预后不良相关。H19的异位表达促进了大肠癌细胞在体内外的转移，并诱导了上皮细胞向间质细胞转化（EMT）。在机制上，H19直接结合hnRNPA 2B 1。hnRNPA 2B 1的敲低减弱了H19诱导的CRC细胞的迁移和侵袭。结论H19/hnRNPA 2B 1/EMT轴在大肠癌转移中的作用，提示H19可能是一个潜在的预测大肠癌预后的生物标志物，也可能是一种治疗大肠癌的策略。
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.