CircSETD3 (Hsa_circ_0000567) acts as a sponge for microRNA-421 inhibiting hepatocellular carcinoma growth
CircSETD3 (Hsa_circ_0000567) acts as a sponge for microRNA-421 inhibiting hepatocellular carcinoma growth
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CircSETD3 (Hsa_circ_0000567) 作为 microRNA-421 的海绵抑制肝细胞癌生长
DOI：
10.1186/s13046-019-1041-2
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发表时间：
2019-02-22
影响因子：
11.3
通讯作者：
Xu, Mingqing
中科院分区：
文献类型：
--
作者：
Xu, Liangliang;Feng, Xinfu;Xu, Mingqing
研究背景环状RNA（CircRNA）在肿瘤的发生、发展中起重要作用。然而，circRNA在肝细胞癌（HCC）中的表达谱和功能在很大程度上是不清楚的。使用Kaplan-Meier方法绘制生存曲线，并使用对数秩检验进行比较。通过桑格测序、趋异引物PCR和RNase R处理确认候选circRNA的环状结构。在体外和体内评价HCC细胞的增殖。结果肝癌组织和肝癌细胞系中CircSETD 3（hsa_circRNA_0000567/hsa_circRNA_101436）表达显著下调，与对照组相比差异有统计学意义（P < 0. 05）。circSETD 3在HCC组织中的低表达显著预测不良预后，并且与患者中较大的肿瘤大小和低分化HCC相关。体外实验表明，circSETD 3能抑制肝癌细胞的增殖，并诱导肝癌细胞发生G1/S期阻滞。体内研究表明，circSETD 3在异种移植小鼠模型中稳定过表达，并抑制HCC的生长。结论CircSETD 3是一种新的肝癌肿瘤抑制因子，是一种有价值的预后生物标志物。此外，circSETD 3抑制HCC的生长部分通过circSETD 3/miR-421/MAPK 14途径。
BackgroundCircular RNAs (circRNAs) play important roles in tumourigenesis and tumour progression. However, the expression profiles and functions of circRNAs in hepatocellular carcinoma (HCC) are largely unclear.MethodsThe expression profiles of circRNAs in HCC were identified through microarray analysis and were validated through quantitative reverse transcription polymerase chain reaction (qRT-PCR). Survival curves were plotted using the Kaplan-Meier method and compared using the log-rank test. The circular structure of candidate circRNA was confirmed through Sanger sequencing, divergent primer PCR, and RNase R treatments. Proliferation of HCC cells was evaluated in vitro and in vivo. The microRNA (miRNA) sponge mechanism of circRNAs was demonstrated using dual-luciferase reporter and RNA immunoprecipitation assays.ResultsCircSETD3 (hsa_circRNA_0000567/hsa_circRNA_101436) was significantly downregulated in HCC tissues and cell lines. Low expression of circSETD3 in HCC tissues significantly predicted an unfavourable prognosis and was correlated with larger tumour size and poor differentiation of HCC in patients. In vitro experiments showed that circSETD3 inhibited the proliferation of HCC cells and induced G1/S arrest in HCC cells. In vivo studies revealed that circSETD3 was stably overexpressed in a xenograft mouse model and inhibited the growth of HCC. Furthermore, we demonstrated that circSETD3 acts as a sponge for miR-421 and verified that mitogen-activated protein kinase (MAPK)14 is a novel target of miR-421.ConclusionCircSETD3 is a novel tumour suppressor of HCC and is a valuable prognostic biomarker. Moreover, circSETD3 inhibits the growth of HCC partly through the circSETD3/miR-421/MAPK14 pathway.