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lncRNA LINC00460 Silencing Represses EMT in Colon Cancer through Downregulation of ANXA2 via Upregulating miR-433-3p.
Molecular Therapy - Nucleic Acids ( IF 8.8 ) Pub Date : 2019-12-18 , DOI: 10.1016/j.omtn.2019.12.006
Weiwen Hong 1 , Hongan Ying 2 , Feng Lin 3 , Ruliang Ding 1 , Weiya Wang 1 , Meng Zhang 3
Affiliation  

Colon cancer (CC), one of the major causes of tumor-associated death, is often presented with a heterogenic pool of cells with unique differentiation patterns. This study explored the functions that LINC00460 displayed in CC by regulating microRNA-433-3p (miR-433-3p) and ANXA2. LINC00460 expression was either silenced or overexpressed in HCT-116 and LOVO cells to explore the functional roles of LINC00460 in CC. The relationship between miR-433-3p and LINC00460/ANXA2 was analyzed using dual-luciferase reporter assay, RNA-pull down, and RIP assays. Cell proliferation, metastasis, invasion, and apoptosis were examined in vitro, and tumorigenicity was evaluated in vivo following LINC00460 silencing. Additionally, the regulatory mechanisms were investigated using LINC00460 and ANXA2 gain- or loss-of-function experiments. We found that LINC00460 was expressed highly in CC. Down-regulation of LINC00460 inhibited cell invasion and proliferation in vitro and restrained tumor growth in vivo. Moreover, LINC00460 was able to specifically bind to miR-433-3p to increase the expression of ANXA2. Furthermore, LINC00460 upregulated the E-cadherin expression and downregulated the vimentin and N-cadherin expression by upregulating ANXA2, therefore inducing epithelial-mesenchymal transition. These findings suggested that LINC00460 might function as an oncogenic lncRNA in CC development and could be explored as a potential biomarker and therapeutic target for CC.



中文翻译:

lncRNA LINC00460沉默通过上调miR-433-3p来下调ANXA2,从而抑制结肠癌中的EMT。

结肠癌(CC)是肿瘤相关死亡的主要原因之一,经常表现为具有独特分化模式的异质细胞池。这项研究探索了LINC00460通过调控microRNA-433-3p(miR-433-3p)和ANXA2在CC中显示的功能。LINC00460表达在HCT-116和LOVO细胞中沉默或过表达,以探索LINC00460在CC中的功能。使用双荧光素酶报告基因分析,RNA下拉和RIP分析分析了miR-433-3p与LINC00460 / ANXA2之间的关系。在体外检查细胞增殖,转移,侵袭和凋亡,并在LINC00460沉默后在体内评估致瘤性。此外,使用LINC00460和ANXA2功能获得或丧失实验研究了调节机制。我们发现LINC00460在CC中得到了高度表达。LINC00460的下调在体外抑制细胞侵袭和增殖,并在体内抑制肿瘤的生长。此外,LINC00460能够与miR-433-3p特异性结合,从而增加ANXA2的表达。此外,LINC00460通过上调ANXA2上调E-钙粘蛋白表达,并下调波形蛋白和N-钙粘蛋白表达,从而诱导上皮-间质转化。这些发现表明,LINC00460可能在CC的发展中起致癌作用的lncRNA的作用,并可能被探索为CC的潜在生物标志物和治疗靶标。LINC00460能够与miR-433-3p特异性结合,从而增加ANXA2的表达。此外,LINC00460通过上调ANXA2上调E-钙粘蛋白表达,并下调波形蛋白和N-钙粘蛋白表达,从而诱导上皮-间质转化。这些发现表明,LINC00460可能在CC的发展中起着致癌作用的lncRNA的作用,并有望作为CC的潜在生物标志物和治疗靶点进行探索。LINC00460能够与miR-433-3p特异性结合,从而增加ANXA2的表达。此外,LINC00460通过上调ANXA2上调E-钙粘蛋白表达,并下调波形蛋白和N-钙粘蛋白表达,从而诱导上皮-间质转化。这些发现表明,LINC00460可能在CC的发展中起着致癌作用的lncRNA的作用,并有望作为CC的潜在生物标志物和治疗靶点进行探索。

更新日期:2019-12-18
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