Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis.
Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis.
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环状RNA circSDHC作为miR-127-3p的海绵通过CDKN3/E2F1轴促进肾细胞癌的增殖和转移
DOI：
10.1186/s12943-021-01314-w
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发表时间：
2021-01-20
期刊：
影响因子：
37.3
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Cen J;Liang Y;Huang Y;Pan Y;Shu G;Zheng Z;Liao X;Zhou M;Chen D;Fang Y;Chen W;Luo J;Zhang J
背景越来越多的证据表明，circular RNA（circular RNA）在肿瘤的发生、发展中具有重要的调控作用，然而，circular RNA在肾细胞癌（renal cell carcinoma，RCC）中的表达模式和生物学功能尚不清楚。对在线circRNA微阵列数据集和我们自己的患者队列的分析表明，circSDHC（hsa_circ_0015004）在RCC中具有潜在的致癌作用。随后，通过qPCR测定法测量RCC组织和细胞系中的circSDHC表达，并评估circSDHC的预后价值。此外，进行了一系列功能性体外和体内实验以评估circSDHC对RCC增殖和转移的影响。采用RNA pull-down法、荧光素酶报告基因法和荧光原位杂交法检测circSDHC、miR-127- 3 p及其靶基因之间的相互作用。此外，circSDHC在体内和体外均促进肿瘤细胞增殖和侵袭。对circSDHC在RCC中作用的潜在机制的分析表明，它与miR-127- 3 p竞争性结合，并阻止其对下游基因CDKN 3和E2 F1通路的抑制，从而导致RCC恶性进展。此外，敲低circSDHC导致CDKN 3表达和E2 F1通路抑制减少，这可以通过治疗与miR-127- 3 p inhibitor.ConclusionOur data indicates，for the first time，a essential role for the circSDHC/miR-127- 3 p/CDKN 3/E2 F1 axis in RCC progression.因此，circSDHC有可能成为RCC患者的新治疗靶点。
BackgroundThere is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive.MethodBioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes.ResultsClinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene,CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor.ConclusionOur data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.
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