CircSTK39通过调节miR-135a-5p / NR3C2介导的上皮 - 间充质转化信号通路,抑制膀胱癌的增殖和侵袭。
CircSTK39 suppresses the proliferation and invasion of bladder cancer by regulating the miR-135a-5p/NR3C2-mediated epithelial-mesenchymal transition signaling pathway.
发表日期:2022 Dec 20
作者:
Zhi Li, Zejin Wang, Shaobo Yang, Chong Shen, Yinglang Zhang, Runxue Jiang, Zhe Zhang, Yu Zhang, Hailong Hu
来源:
CELL BIOLOGY AND TOXICOLOGY
摘要:
Circular RNAs(circRNA)是新型的非编码RNA,它们在肿瘤发展中起着关键作用,包括膀胱癌(BCa)。然而,circRNA在介导BCa上皮-间充质转化(EMT)过程的作用和潜在的分子机制尚未研究。在本研究中,我们首次发现一种新的circRNA,circSTK39(称为has_circ_0001079),它是基于高通量RNA测序结果得出的下调基因。随后,我们确定了BCa组织和其细胞系中circSTK39的表达显著降低。此外,较低的circSTK39表达与BCa患者的预后较差密切相关。接下来,我们通过体内和体外的失、增实验检测了circSTK39的生物学功能。circSTK39的异位表达降低了细胞增殖、集落形成和侵袭能力,而circSTK39的沉默则防止了上述表型。从机械上讲,circSTK39可以与miR-135a-5p结合,从而抑制NR3C2介导的BCa进程中的EMT过程。总之,我们的研究结果表明,circSTK39通过miR-135a-5p/NR3C2轴抑制BCa细胞的EMT,并可能成为BCa诊断的有前途的生物标志物或治疗靶点。© 2022。作者(们)在Springer Nature B.V.独家许可下发表。
Circular RNAs (circRNAs) serve as novel noncoding RNAs that have crucial functions in the development of tumors, including those from bladder cancer (BCa). However, the role and underlying molecular mechanism of circRNAs in mediating the epithelial-mesenchymal transition (EMT) processes in BCa have yet to be studied. In this research, we first found a novel circRNA, circSTK39 (termed as has_circ_0001079), which was a downregulated gene based on the results of high-throughput RNA sequencing. Subsequently, we determined that the expression of circSTK39 in BCa tissues and their cell lines was significantly reduced. In addition, lower circSTK39 expression was strongly related to a worse prognosis for BCa patients. Next, we detected the biological functions of circSTK39 by using loss and gain experiments in vitro and in vivo. Ectopic expression of circSTK39 decreased cell proliferation, colony formation, and invasion capacities, while circSTK39 knockdown prevented the above phenotypes. Mechanically, circSTK39 could sponge with miR-135a-5p, thus inhibiting NR3C2-mediated EMT processes in the BCa progression. In conclusion, our results revealed that circSTK39 inhibited EMT of BCa cells through the miR-135a-5p/NR3C2 axis and may provide promising biomarkers for the diagnosis or prospective therapeutic targets for BCa.© 2022. The Author(s), under exclusive licence to Springer Nature B.V.