Abstract
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.
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All data generated or analyzed during this study are included in this published article and its supplementary information files.
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The authors thank AiMi Academic Services (www.aimieditor.com) for the English language editing and review services.
Funding
The present study received financial support from the Natural Science Foundation Project of Tianjin (grant no. 18PTLCSY00010), the Tianjin Urological Key Laboratory Foundation (grant no. 2017ZDSYS13 and 2018ZDSYS12), the Key Clinical Research Project of the Second Hospital of Tianjin Medical University (grant no. 2019LC04), and the Youth Fund of Tianjin Medical University Second Hospital (grant no. 2020ydey09).
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Zhi li, Zejin Wang, and Shaobo Yang performed the experiments and generated the data. Chong Shen, Yinglang Zhang, Runxue Jiang, and Zhe Zhang analyzed the data. Zhi li, Zejin Wang, and Shaobo Yang designed the experiments. Zhi li wrote the manuscript. Hailong Hu revised the manuscript. All authors contributed to the article. All authors read and approved the final manuscript.
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Participants were asked to sign informed consent before using clinical resources. The present study was approved by the Ethics Committee of the second Hospital of Tianjin Medical University (NO.KY2020K063).
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Highlights
hsa_circ_0001079 is downregulated in BCa and predicts higher likelihood of survival of bladder cancer.
hsa_circ_0001079 overexpression in BCa cells inhibits progression and metastasis of bladder cancer in vitro and in vivo.
hsa_circ_0001079 can regulate NR3C2 expression by competitively interacting with miR-135a-5p.
hsa_circ_0001079 inhibits the epithelial-mesenchymal transition signaling pathway, and it might be a novel therapeutic target for BCa.
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Li, Z., Wang, Z., Yang, S. et al. CircSTK39 suppresses the proliferation and invasion of bladder cancer by regulating the miR-135a-5p/NR3C2-mediated epithelial-mesenchymal transition signaling pathway. Cell Biol Toxicol 39, 1815–1834 (2023). https://doi.org/10.1007/s10565-022-09785-3
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DOI: https://doi.org/10.1007/s10565-022-09785-3