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首页> 外文期刊>EBioMedicine >Circular RNA circPICALM sponges miR-1265 to inhibit bladder cancer metastasis and influence FAK phosphorylation
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Circular RNA circPICALM sponges miR-1265 to inhibit bladder cancer metastasis and influence FAK phosphorylation

机译:环状RNA circPICALM海绵miR-1265抑制膀胱癌转移并影响FAK磷酸化

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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. Fund This research was supported by National Natural Science Foundation of China, No.81772728, National Natural Science Foundation of China, No.81772719, National Natural Science Foundation of China No.81572514.
机译:背景转移是治疗膀胱癌(BC)的主要障碍。环状RNA在癌症的侵略性生物学行为中发挥多种功能。在这项研究中,我们旨在阐明circPICALM如何影响BC转移。方法采用实时荧光定量PCR分析circPICALM的表达。使用体外迁移,侵袭和伤口愈合测定以及体内足垫模型评估BC细胞的致瘤性。 circPICALM和miR-1265之间的相互作用已通过下拉和双荧光素酶报告基因检测以及生物素标记的miRNA捕获得到证实。通过共免疫沉淀证实了STEAP4和粘着斑激酶(FAK)的相互作用。结果发现BC组织中CircPICALM被下调,而circPICALM的低表达与晚期T期,高分期,淋巴结阳性和较差的总生存率有关。 circPICALM的过表达抑制了BC细胞的转移,而DHX9负调控circPICALM的水平。 CircPICALM与miR-1265共定位,并充当该miRNA的海绵,而circPICALM过表达消除了miR-1265的前侵袭作用。靶向miR-1265的STEAP4可抑制转移。它与FAK结合以防止Y397处的自磷酸化,并影响BC细胞中的EMT。解释CircPICALM可抑制BC转移并与miR-1265结合以阻断其促侵袭活性。 STEAP4是miR-1265的靶标,与FAK磷酸化和EMT有关。基金资助:国家自然科学基金:81772728,国家自然科学基金:81772719,国家自然科学基金:81572514。

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