FSCN1/METTL3/TLN1 axis promotes the malignant progression in bladder carcinoma

Abstract

Background The RNA-binding protein (RBP) played an important role in tumors. FSCN1 functioned as an oncogene in bladder carcinoma (BLCA). FSCN1 has not been reported as an RBP in BLCA. The mechanism by which FSCN1 promoted BLCA invasion and metastasis has remained unclear. Methods The FSCN1-bound RNAs in BLCA cell lines were identified using RIP-sequencing. The regulatory relationship between FSCN1 and METTL3 or TLN1 was verified by RNA immunoprecipitation (RIP), RNA pulldown assay, co-immunoprecipitation (Co-IP), western blotting, quantitative real-time PCR (qRT-PCR) and immunofluorescence. The metastatic abilities of the BCLA cells were evaluated by in vitro wound healing and transwell assays, as well as in vivo models. Results TLN1 protein levels were higher in BLCA tissues compared to the paired para-tumor tissues, whereas its mRNA expression was lower in the tumors. Mechanistically, FSCN1 bound to and upregulated METTL3, which in turn repressed TLN1 mRNA expression through the latter’s 3'UTR. In addition, FSCN1 bound to the CDS region of TLN1 mRNA and promoted its translation. Knocking down FSCN1, METTL3 and TLN1 individually had an inhibitory effect on the proliferation, invasion, migration and metastasis of BLCA cells. Conclusions FSCN1 functions as an RBP to promote proliferation, invasion and migration of BLCA cells. The FSCN1/METTL3/TLN1 axis is a potential therapeutic target for BLCA.