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Invasion-related circular RNA circFNDC3B inhibits bladder cancer progression through the miR-1178-3p/G3BP2/SRC/FAK axis.

ABSTRACT: BACKGROUND:Increasing 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. METHODS:A 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. RESULTS:In 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. CONCLUSIONS:CircFNDC3B may serve as a novel tumor suppressive factor and potential target for new therapies in human BC.

SUBMITTER: Liu H

PROVIDER: S-EPMC6245936 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Invasion-related circular RNA circFNDC3B inhibits bladder cancer progression through the miR-1178-3p/G3BP2/SRC/FAK axis.

Liu Hongwei H Bi Junming J Dong Wei W Yang Meihua M Shi Juanyi J Jiang Ning N Lin Tianxin T Huang Jian J

Molecular cancer 20181120 1

<h4>Background</h4>Increasing 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.<h4>Methods</h4>A 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. Funct ...[more]

PMID: 30458784

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Project description:BackgroundIncreasing evidence has suggested that dysregulation of certain microRNAs (miRNAs) may contribute to human disease including carcinogenesis and tumor metastasis in human. miR-124-3p is down-regulated in various cancers, and modulates proliferation and aggressiveness of cancer cells. However, the roles of miR-124-3p in human bladder cancer are elusive. Thus, this study was conducted to investigate the biological functions and its molecular mechanisms of miR-124-3p in human bladder cancer cell lines, discussing whether it has a potential to be a therapeutic biomarker of bladder cancer.MethodsThree human bladder cancer cell lines and samples from ten patients with bladder cancer were analyzed for the expression of miR-124-3p by quantitative RT--PCR. Exogenetic overexpression of miR-124-3p was established by transfecting mimics into T24, UM-UC-3 and J82 cells, after that cell proliferation and cell cycle were assessed by MTT assay, flow cytometry and Colony-forming assay. Cell motility and invasion ability were evaluated by wound healing assay and transwell assay. Tissue microarray, and immunohistochemistry with antibodies against ROCK1, MMP2 and MMP9 was performed using the peroxidase and DAB methods. The target gene of miR-124-3p was determined by luciferase assays, quantitative RT--PCR and western blot. The regulation of epithelial-to-mesenchymal transition by miR-124-3p was analyzed by western blot.ResultsmiR-124-3p is frequently down-regulated in bladder cancer both in three bladder cancer cell lines, T24, UM-UC-3, J82 and clinical samples. Overexpression of miR-124-3p induced G1-phase arrest in T24, UM-UC-3 and J82 cell lines and suppressed cell growth in colony-forming assay. miR-124-3p significantly repressed the capability of migration and invasion of bladder cancer cells. In addition, ROCK1 was identified as a new target of miR-124-3p. ROCK1, MMP2, MMP9 were up-regulated in bladder cancer tissues. Furthermore, we demonstrated miR-124-3p could inhibit bladder cancer cell epithelial mesenchymal transfer, and regulated the expression of c-Met, MMP2, MMP9.ConclusionsmiR-124-3p can repress the migration and invasion of bladder cancer cells via regulating ROCK1. Our data indicate that miR-124-3p could be a tumor suppressor and may have a potential to be a diagnostics or predictive biomarker in bladder cancer.

Dataset Information

Invasion-related circular RNA circFNDC3B inhibits bladder cancer progression through the miR-1178-3p/G3BP2/SRC/FAK axis.

Publications

Invasion-related circular RNA circFNDC3B inhibits bladder cancer progression through the miR-1178-3p/G3BP2/SRC/FAK axis.

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