Circ-AKT3 inhibits clear cell renal cell carcinoma metastasis via altering miR-296-3p/E-cadherin signals
Circ-AKT3 inhibits clear cell renal cell carcinoma metastasis via altering miR-296-3p/E-cadherin signals
复制标题
Circ-AKT3 通过改变 miR-296-3p/E-cadherin 信号抑制透明细胞肾细胞癌转移
DOI：
10.1186/s12943-019-1072-5
复制
发表时间：
2019-11-01
期刊：
影响因子：
37.3
通讯作者：
Xia, Liqun
中科院分区：
文献类型：
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作者：
Xue, Dingwei;Wang, Huan;Xia, Liqun
研究背景环状RNA（circRNA）是一类通过特殊选择性剪接产生的环状内源RNA，参与多种疾病的进展。然而，circRNA在透明细胞肾细胞癌（ccRCC）中的作用仍鲜有报道。方法我们使用环状RNA微阵列检测ccRCC中较低的circ-AKT3表达。然后，应用qPCR阵列验证60个ccRCC组织和邻近正常组织以及ccRCC细胞系和人正常肾细胞（HK-2）之间circ-AKT3的表达。我们在体外和体内研究了circ-AKT3在ccRCC中的功能，并通过Western blotting、生物信息学分析、RNA Pull-down实验和荧光素酶报告基因实验检测了其潜在机制。结果证实Circ-AKT3在ccRCC中显着下调。 circ-AKT3的敲低促进ccRCC迁移和侵袭，而circ-AKT3的过表达抑制ccRCC转移。此外，circ-AKT3/miR-296-3p/E-cadherin 轴被证明负责 circ-AKT3 抑制 ccRCC 转移。 结论 Circ-AKT3 通过竞争性结合 miR-296-3p 强制 E-cadherin 表达来抑制 ccRCC 转移。因此，Circ-AKT3 可能作为一种新的治疗方法来更好地抑制 ccRCC 转移。
BackgroundCircular RNA (circRNA) is a type of circular endogenous RNA produced by special selective splicing and participates in progression of diverse diseases. However, the role of circRNA in clear cell renal cell carcinoma (ccRCC) is still rarely reported.MethodsWe detected lower circ-AKT3 expression in ccRCC using the circular RNA microarray. Then, qPCR array was applied to verify the expression of circ-AKT3 in between 60 ccRCC tissues and adjacent normal tissues, as well as ccRCC cell lines and human normal kidney cell (HK-2). We investigated the function of circ-AKT3 in ccRCC in vitro and in vivo and detected underlying mechanisms by Western blotting, bioinformatic analysis, RNA pull-down assay and luciferase reporter assay.ResultsCirc-AKT3 was verified significantly downregulated in ccRCC. Knockdown of circ-AKT3 promoted ccRCC migration and invasion, while overexpression of circ-AKT3 suppressed ccRCC metastasis. Further, circ-AKT3/miR-296-3p/E-cadherin axis was shown responsible for circ-AKT3 inhibiting ccRCC metastasis.ConclusionCirc-AKT3 suppresses ccRCC metastasis by enforcing E-cadherin expression through competitively binding miR-296-3p. Circ-AKT3 may therefore serve as a novel therapeutic to better suppress ccRCC metastasis.