circFBLIM1 act as a ceRNA to promote hepatocellular cancer progression by sponging miR-346.
circFBLIM1 act as a ceRNA to promote hepatocellular cancer progression by sponging miR-346.
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DOI：
10.1186/s13046-018-0838-8
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发表时间：
2018-07-27
期刊：
影响因子：
--
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Bai N;Peng E;Qiu X;Lyu N;Zhang Z;Tao Y;Li X;Wang Z
越来越多的证据表明，环状RNA（circular RNA，circRNA）作为一类非编码RNA，在肿瘤的发生发展中起着重要作用。然而，circRNA在肝细胞癌（HCC）中的功能在很大程度上尚不清楚。我们使用circRNA微阵列来鉴定在HCC组织中异常表达的circRNA。通过定量实时PCR（qRT-PCR）检测HCC细胞系和组织中显著上调的circRNA（circFBLM 1）的表达水平。然后，我们通过细胞增殖、凋亡、侵袭和小鼠异种移植实验来检测circFBLM 1在肝癌中的功能。另外，采用荧光素酶法和RNA免疫沉淀法（RIP）检测circFBLIM 1在肝癌中的miRNA海绵功能。微阵列分析和qRT-PCR验证了在HCC组织和细胞系中上调的称为circFBLIM 1的circRNA。敲低circFBLIM 1可抑制肝癌细胞的增殖、侵袭并促进凋亡。通过荧光素酶报告基因测定，观察到circFBLM 1和FBLM 1直接结合miR-346。随后的实验表明，circFBLIM 1和FBLIM 1通过海绵状的miR-346来调节彼此的表达。综上所述，我们得出结论，circFBLIM 1可能作为竞争性内源性RNA（ceRNA）通过海绵状miR-346发挥HCC中的调节功能来调节FBLIM 1的表达。circFBLIM 1可能是一种诊断性生物标志物和潜在的肝癌治疗靶点。
Accumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in hepatocellular cancer (HCC) is largely unknown. We performed circRNA microarrays to identify circRNAs that are aberrantly expressed in HCC tissues. Expression levels of a significantly upregulated circRNA, circFBLIM1, was detected by quantitative real-time PCR (qRT-PCR) in HCC cell lines and tissues. Then, we examined the functions of circFBLIM1 in HCC by cell proliferation, apoptosis, invasion and mouse xenograft assay. In addition, luciferase assay and RNA immunoprecipitation (RIP) assay were used to explore the miRNA sponge function of circFBLIM1 in HCC. Microarray analysis and qRT-PCR verified a circRNA termed circFBLIM1 that was upregulated in HCC tissues and cell lines. Knockdown of circFBLIM1 inhibited proliferation, invasion and promoted apoptosis in HCC. Via luciferase reporter assays, circFBLIM1 and FBLIM1 were observed to directly bind to miR-346. Subsequent experiments showed that circFBLIM1 and FBLIM1 regulated the expression of each other by sponging miR-346. Taken together, we conclude that circFBLIM1 may function as a competing endogenous RNA (ceRNA) to regulate FBLIM1 expression through sponging miR-346 to exert regulatory functions in HCC. circFBLIM1 may be a diagnostic biomarker and potential target for HCC therapy.
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