Invasion-related circular RNA circFNDC3B inhibits bladder cancer progression through the miR-1178-3p/G3BP2/SRC/FAK axis.
Invasion-related circular RNA circFNDC3B inhibits bladder cancer progression through the miR-1178-3p/G3BP2/SRC/FAK axis.
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侵袭相关环状RNA circFNDC3B通过miR-1178-3p/G3BP2/SRC/FAK轴抑制膀胱癌进展
DOI：
10.1186/s12943-018-0908-8
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发表时间：
2018-11-20
期刊：
影响因子：
37.3
通讯作者：
Huang J
中科院分区：
文献类型：
--
作者：
Liu H;Bi J;Dong W;Yang M;Shi J;Jiang N;Lin T;Huang J
研究背景越来越多的证据表明，环状RNA（circular RNA，circRNA）在肿瘤生物学中起着重要作用.然而，circFNDC 3B在膀胱癌（BC）中的作用和潜在的调控机制仍然未知。MethodsA细胞侵袭模型建立了重复transwell检测，并通过入侵模型，入侵相关的circRNA在BC中进行了鉴定。采用实时荧光定量PCR检测82例乳腺癌组织和细胞系中circFNDC 3B的表达。进行功能测定以评估circFNDC 3B对体外增殖、迁移和侵袭以及对体内肿瘤发生和转移的影响。通过荧光原位杂交、pull-down实验和荧光素酶报告基因实验证实了circFNDC 3B和miR-1178- 3 p之间的关系。我们发现circFNDC 3B在BC组织中显著下调，并且与病理T分期、分级、淋巴结浸润和患者的总生存率相关。在功能上，过表达circFNDC 3B在体外和体内均显著抑制增殖、迁移和侵袭。从机制上讲，circFNDC 3B可以直接结合miR-1178- 3 p，其靶向癌基因G3 BP 2的5′UTR。结论CircFNDC 3B可能是一种新的肿瘤抑制因子，有望成为治疗乳腺癌的新靶点。
BackgroundIncreasing evidence has revealed that circular RNAs (circRNAs) play crucial roles in cancer biology. However, the role and underlying regulatory mechanisms of circFNDC3B in bladder cancer (BC) remain unknown.MethodsA cell invasion model was established by repeated transwell assays, and invasion-related circRNAs in BC were identified through an invasion model. The expression of circFNDC3B was detected in 82 BC tissues and cell lines by quantitative real-time PCR. Functional assays were performed to evaluate the effects of circFNDC3B on proliferation, migration and invasion in vitro-, and on tumorigenesis and metastasis in vivo. The relationship between circFNDC3B and miR-1178-3p was confirmed by fluorescence in situ hybridization, pull-down assay and luciferase reporter assay.ResultsIn the present study, we identified a novel circRNA (circFNDC3B) through our established BC cell invasion model. We found that circFNDC3B was dramatically downregulated in BC tissues and correlated with pathological T stage, grade, lymphatic invasion and patients’ overall survival rate. Functionally, overexpression of circFNDC3B significantly inhibited proliferation, migration and invasion both in vitro and in vivo. Mechanistically, circFNDC3B could directly bind to miR-1178-3p, which targeted the 5′UTR of the oncogene G3BP2. Moreover, circFNDC3B acted as a miR-1178-3p sponge to suppress G3BP2, thereby inhibiting the downstream SRC/FAK signaling pathway.ConclusionsCircFNDC3B may serve as a novel tumor suppressive factor and potential target for new therapies in human BC.
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