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

Abstract

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.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0908-8) contains supplementary material, which is available to authorized users.

hsa_circRNA_100533 regulates GNAS by sponging hsa_miR_933 to prevent oral squamous cell carcinoma

“…circRNA is one kind of endogenous noncoding RNA, which can stably exist in mammals. circRNAs are recently found to be involve in the development of numerous diseases, especially cancers . It was showed that OSCC tissues have abundant circRNAs, and multiple circRNAs significantly differentially expressed.…”

“…circRNAs are recently found to be involve in the development of numerous diseases, especially cancers. 20,21 It was showed that OSCC tissues have abundant circRNAs, and multiple circRNAs significantly differentially expressed. It was reported that hsa_circ_0008309 and hsa_circ_001242 was significantly downregulated in OSCC tissues, correlated with pathological differentiation of OSCC, and may act as a potential novel biomarker for the diagnosis and treatment of OSCC.…”

Tumor‐suppressive circular RNAs: Mechanisms underlying their suppression of tumor occurrence and use as therapeutic targets

“…A study found that circFNDC3B is significantly downregulated in BCa tissues and is associated with pathological T staging, grading, lymphatic invasion, and overall patient survival . Mechanistically, circFNDC3B binds directly to miR‐1178‐3p, which targets oncogene G3BP stress granule assembly factor 2 (G3BP2) mRNA .…”

“…A study found that circFNDC3B is significantly downregulated in BCa tissues and is associated with pathological T staging, grading, lymphatic invasion, and overall patient survival . Mechanistically, circFNDC3B binds directly to miR‐1178‐3p, which targets oncogene G3BP stress granule assembly factor 2 (G3BP2) mRNA . Another BCa‐associated circRNA, circITCH was found to be reduced in BCa tissues and cell lines, and expression of P21 and phosphatase and tensin homolog (PTEN) was upregulated by sponging of miR‐17 and miR‐224 .…”

circRNAs expressed in human peripheral blood are associated with human aging phenotypes, cellular senescence and mouse lifespan

“…An average person may lose~20-40% of skeletal muscle mass as well as muscle strength from by the time they reach 80 years of age (Carmeli et al 2002;Doherty 2003) and decline in skeletal muscle strength is predictive of disability and mortality in humans (Giampaoli et al 1999;Rantanen et al 1999;Rantanen et al 2012). Circular RNAs originating from this gene have been reported previously, and suggested to possess tumour suppressor activity (Liu et al 2018).…”