Circular RNA circPICALM sponges miR-1265 to inhibit bladder cancer metastasis and influence FAK phosphorylation
Circular RNA circPICALM sponges miR-1265 to inhibit bladder cancer metastasis and influence FAK phosphorylation
复制标题
环状RNA circPICALM海绵miR-1265抑制膀胱癌转移并影响FAK磷酸化
DOI：
10.1016/j.ebiom.2019.08.074
复制
发表时间：
2019-10-01
期刊：
影响因子：
11.1
通讯作者：
Huang, Jian
中科院分区：
文献类型：
--
作者：
Yan, Dong;Dong, Wei;Huang, Jian
Background: Metastasis is a major obstacle in the treatment of bladder cancer (BC). Circular RNAs exert various functions in the aggressive biological behaviour of cancers. In this study, we aimed to elucidate how circPICALM influences BC metastasis.Methods: The expression of circPICALM was analysed by real-time PCR. The tumourigenic properties of BC cells were evaluated using in vitro migration, invasion, and wound healing assays and an in vivo footpad model. The interaction between circPICALM and miR-1265 was confirmed by pull-down and dual-luciferase reporter assays and biotin-labelled miRNA capture. The interaction of STEAP4 and focal adhesion kinase (FAK) was confirmed by co-immunoprecipitation.Findings: CircPICALM was downregulated in BC tissues, and low circPICALM expression was related to advanced T stage, high grade, lymph node positivity and poor overall survival. Overexpression of circPICALM inhibited the metastasis of BC cells, and DHX9 negatively regulated circPICALM levels. CircPICALM colocalized with miR-1265 and acted as a sponge for this miRNA, and the pro-invasion effect of miR-1265 was abolished by circPICALM overexpression. STEAP4, a target of miR-1265, suppressed metastasis; it bound to FAK to prevent autophosphorylation at Y397 and influenced EMT in BC cells.Interpretation: CircPICALM can inhibit BC metastasis and bind to miR-1265 to block its pro-invasion activity. STEAP4 is a target of miR-1265 and is related to FAK phosphorylation and EMT. (C) 2019 The Authors. Published by Elsevier B.V.
