Department of Urinary Surgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, 121000, China.
J Egypt Natl Canc Inst. 2024 Mar 18;36(1):8. doi: 10.1186/s43046-024-00206-6.
CircRNAs and miRNAs are involved in the progression of tumor. CircMCTP2 is considered as a novel tumor promoter. However, the exact functions of circMCTP2 in bladder cancer are still unclear. This study was designed to explore the underlying mechanisms of circMCTP2-modulated tumor development in bladder cancer.
The present study is an original research. The levels of circMCTP2 in a total of 39 bladder cancer specimens and cell lines were determined by RT-qPCR. The expression of FZD8 in T24 and RT-4 cells treated with miR-99a-5p mimics were examined using western blotting. In addition, the proliferative, migrative and invasive abilities of transfected cells were determined by CCK8 and Transwell assays. Furthermore, the apoptosis of transfected cells was evaluated using flow cytometry. Dual luciferase reporter assay was performed to elucidate the relationship between miR-99a-5p and circMCTP2/FZD8.
The levels of circMCTP2 were elevated in bladder cancer samples and cells, and this was related to worse survival rate. Downregulation of circMCTP2 suppressed growth and metastasis of cells, whereas the apoptotic rate of cells was enhanced. The levels of miR-99a-5rp was elevated after the downregulation of circMCTP2. Moreover, reverse correlation between the expression of miR-99a-5p and circMCTP2 was revealed in bladder cancer specimens. Additionally, FZD8 was the putative target of miR-99a-5p and the mimics of miR-99a-5p inhibited the proliferation, migration and invasion of bladder cancer cells via the FZD8/Wnt-b-catenin axis. Moreover, circMCTP2 regulated the growth and metastasis of bladder cancer cells potentially through regulating the miR-99a-5p/FZD8/Wnt-b-catenin axis. In summary, circMCTP2 was considered as an oncogenic factor through regulating the miR-99a-5p/FZD8/Wnt-b-catenin axis.
This novel signaling could regulate the biological behaviours of bladder cancer cells, and these findings highlighted circMCTP2 as a critical target for treating bladder cancer.
circRNAs 和 miRNAs 参与肿瘤的进展。CircMCTP2 被认为是一种新型的肿瘤促进物。然而，circMCTP2 在膀胱癌中的确切功能仍不清楚。本研究旨在探讨 circMCTP2 调节膀胱癌肿瘤发展的潜在机制。
本研究为原创研究。通过 RT-qPCR 测定了 39 例膀胱癌标本和细胞系中的 circMCTP2 水平。用 miR-99a-5p 模拟物处理 T24 和 RT-4 细胞后，用 Western blot 检测 FZD8 的表达。此外，通过 CCK8 和 Transwell 测定转染细胞的增殖、迁移和侵袭能力。此外，通过流式细胞术评估转染细胞的凋亡。双荧光素酶报告基因检测阐明了 miR-99a-5p 与 circMCTP2/FZD8 之间的关系。
circMCTP2 在膀胱癌样本和细胞中上调，与生存率较差有关。下调 circMCTP2 抑制细胞生长和转移，而细胞凋亡率增加。circMCTP2 下调后 miR-99a-5p 的水平升高。此外，在膀胱癌标本中揭示了 miR-99a-5p 表达与 circMCTP2 之间的反向相关性。此外，FZD8 是 miR-99a-5p 的假定靶点，miR-99a-5p 的模拟物通过 FZD8/Wnt-β-catenin 轴抑制膀胱癌细胞的增殖、迁移和侵袭。此外，circMCTP2 通过调节 miR-99a-5p/FZD8/Wnt-β-catenin 轴潜在调节膀胱癌细胞的生长和转移。总之，circMCTP2 通过调节 miR-99a-5p/FZD8/Wnt-β-catenin 轴被认为是一种致癌因子。
该新信号通路可调节膀胱癌细胞的生物学行为，这些发现凸显了 circMCTP2 作为治疗膀胱癌的关键靶点。
