lncRNA LINC00460 Silencing Represses EMT in Colon Cancer through Downregulation of ANXA2 via Upregulating miR-433-3p
lncRNA LINC00460 Silencing Represses EMT in Colon Cancer through Downregulation of ANXA2 via Upregulating miR-433-3p
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DOI：
10.1016/j.omtn.2019.12.006
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发表时间：
2020-03-06
影响因子：
8.8
通讯作者：
Zhang, Meng
中科院分区：
文献类型：
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作者：
Hong, Weiwen;Ying, Hongan;Zhang, Meng
结肠癌（CC）是肿瘤相关死亡的主要原因之一，通常表现为具有独特分化模式的异质细胞池。本研究探讨了 LINC00460 通过调节 microRNA-433-3p (miR-433-3p) 和膜联蛋白 A2 (ANXA2) 在 CC 中表现出的功能。 HCT-116 和 LOVO 细胞中 LINC00460 表达沉默或过表达，以探索 LINC00460 在 CC 中的功能作用。使用双荧光素酶报告基因测定、RNA 下拉和 RNA 免疫沉淀 (RIP) 测定分析 miR-433-3p 和 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，还使用 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中高表达。 LINC00460 的下调可抑制体外细胞侵袭和增殖，并抑制体内肿瘤生长。此外，LINC00460能够特异性结合miR-433-3p以增加ANXA2的表达。此外，LINC00460通过上调ANXA2下调E-钙粘蛋白表达并上调波形蛋白和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 发育中充当致癌长非编码 RNA (lncRNA)，并可作为 CC 的潜在生物标志物和治疗靶点进行探索。
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 Annexin A2 (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 RNA immunoprecipitation (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. Downregulation 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 downregulated the E-cadherin expression and upregulated the vimentin and N-cadherin expression by upregulating ANXA2, therefore inducing epithelial-mesenchymal transition. These findings suggested that LINC00460 might function as an oncogenic long non-coding RNA (lncRNA) in CC development and could be explored as a potential biomarker and therapeutic target for CC.