CircMCTP2 通过调控 miR-99a-5p/FZD8 轴促进膀胱癌的进展。

IF 2.1 Q3 ONCOLOGY
Yan Liu, Kexin Zhang, Xianxu Yang
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引用次数: 0

摘要

背景:CircRNA和miRNA参与了肿瘤的进展。circMCTP2被认为是一种新型肿瘤启动子。然而,circMCTP2在膀胱癌中的确切功能仍不清楚。本研究旨在探索 circMCTP2 调节膀胱癌肿瘤发生的潜在机制:本研究为原创性研究。采用 RT-qPCR 方法测定了 39 例膀胱癌标本和细胞系中 circMCTP2 的水平。采用免疫印迹法检测了经 miR-99a-5p 模拟物处理的 T24 和 RT-4 细胞中 FZD8 的表达。此外,还通过 CCK8 和 Transwell 试验测定了转染细胞的增殖、迁移和侵袭能力。此外,还使用流式细胞术评估了转染细胞的凋亡情况。为了阐明 miR-99a-5p 与 circMCTP2/FZD8 之间的关系,还进行了双荧光素酶报告实验:结果:膀胱癌样本和细胞中的 circMCTP2 水平升高,这与生存率降低有关。下调 circMCTP2 可抑制细胞的生长和转移,同时提高细胞的凋亡率。下调 circMCTP2 后,miR-99a-5rp 水平升高。此外,在膀胱癌标本中,miR-99a-5p 和 circMCTP2 的表达呈反向相关。此外,FZD8 是 miR-99a-5p 的假定靶点,miR-99a-5p 的模拟物通过 FZD8/Wnt-b-catenin 轴抑制膀胱癌细胞的增殖、迁移和侵袭。此外,circMCTP2可能通过调节miR-99a-5p/FZD8/Wnt-b-catenin轴来调节膀胱癌细胞的生长和转移。总之,circMCTP2被认为是通过调节miR-99a-5p/FZD8/Wnt-b-catenin轴的致癌因子:结论:这种新的信号传导可调控膀胱癌细胞的生物学行为,这些发现凸显了circMCTP2是治疗膀胱癌的关键靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CircMCTP2 enhances the progression of bladder cancer by regulating the miR-99a-5p/FZD8 axis.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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来源期刊
CiteScore
3.50
自引率
0.00%
发文量
46
审稿时长
11 weeks
期刊介绍: As the official publication of the National Cancer Institute, Cairo University, the Journal of the Egyptian National Cancer Institute (JENCI) is an open access peer-reviewed journal that publishes on the latest innovations in oncology and thereby, providing academics and clinicians a leading research platform. JENCI welcomes submissions pertaining to all fields of basic, applied and clinical cancer research. Main topics of interest include: local and systemic anticancer therapy (with specific interest on applied cancer research from developing countries); experimental oncology; early cancer detection; randomized trials (including negatives ones); and key emerging fields of personalized medicine, such as molecular pathology, bioinformatics, and biotechnologies.
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