The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer.
The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer.
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lncRNA H19 在结直肠癌中充当 miRNA 海绵，促进上皮细胞向间质细胞的转变。
DOI：
10.18632/oncotarget.4154
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发表时间：
2015-09-08
期刊：
影响因子：
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通讯作者：
Waye MM
中科院分区：
文献类型：
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作者：
Liang WC;Fu WM;Wong CW;Wang Y;Wang WM;Hu GX;Zhang L;Xiao LJ;Wan DC;Zhang JF;Waye MM
最近，长链非编码RNA（lncRNA）H19已被鉴定为多种癌症类型中的致癌基因，并且H19的表达升高与肿瘤发生和癌症进展密切相关。然而，这一观察结果的分子基础尚未在结直肠癌（CRC）中得到表征，特别是在上皮向间质转化（EMT）进展期间。在我们的研究中，H19被表征为CRC中EMT的新调节剂。我们发现H19在间充质样癌细胞和原发性结直肠癌组织中高度表达。H19的稳定表达显著促进EMT进展并加速体内和体外肿瘤生长。此外，通过生物信息学研究和RNA免疫沉淀结合荧光素酶报告基因分析，我们证明H19作为miR-138和miR-200 a的竞争性内源性RNA（ceRNA），拮抗它们的功能并导致它们的内源性靶点Vimentin、ZEB 1和ZEB 2的去抑制，所有这些都是间充质细胞的核心标志基因。综上所述，这些观察结果表明，lncRNA H19通过作为竞争性内源性RNA调节参与EMT的多个基因的表达，这可能建立了调控miRNA网络和EMT进展之间缺失的环节。
Recently, the long non-coding RNA (lncRNA) H19 has been identified as an oncogenic gene in multiple cancer types and elevated expression of H19 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in colorectal cancer (CRC) especially during epithelial to mesenchymal transition (EMT) progression. In our studies, H19 was characterized as a novel regulator of EMT in CRC. We found that H19 was highly expressed in mesenchymal-like cancer cells and primary CRC tissues. Stable expression of H19 significantly promotes EMT progression and accelerates in vivo and in vitro tumor growth. Furthermore, by using bioinformatics study and RNA immunoprecipitation combined with luciferase reporter assays, we demonstrated that H19 functioned as a competing endogenous RNA (ceRNA) for miR-138 and miR-200a, antagonized their functions and led to the de-repression of their endogenous targets Vimentin, ZEB1, and ZEB2, all of which were core marker genes for mesenchymal cells. Taken together, these observations imply that the lncRNA H19 modulated the expression of multiple genes involved in EMT by acting as a competing endogenous RNA, which may build up the missing link between the regulatory miRNA network and EMT progression.