Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related death around the world, becoming a severe public health problem. Mounting evidence has proven that circRNAs act as pivotal modulators in the initiation and development of CRC. Although the function of circTADA2A has been explored in osteosarcoma and breast cancer, the specific role of circTADA2A in CRC remains unknown.
Methods: Bioinformatics analysis based on GEO datasets was used to evaluate the dysregulated circRNAs in CRC. CCK-8 and transwell assays were used to detect the functions of CRC cells. qRT-PCR and Western blot were performed to evaluate the expression of RNAs and proteins. Luciferase assay and RNA pull down experiment were carried out to verify the interaction between miR and its targets.
Results: CircTADA2A was downregulated in CRC tissues compared with normal samples. CircTADA2A exhibited greater stability than its linear form when exposed to RNase R and actinomycin D treatment. qRT-PCR analysis validated the lower expression level of circTADA2A in CRC. The loss-of-function and gain-of-function assays indicated that circTADA2A exerted the inhibitory role in CRC cell proliferation and migration. Mechanistically, circTADA2A functioned as a sponge of miR-1229. Further experiments manifested that circTADA2A regulated BCL2L10 expression via competitively binding to miR-1229. More importantly, the tumor suppressor role of circTADA2A in the malignant behaviors of CRC cells was mediated by BCL2L10.
Conclusion: circTADA2A suppressed cell proliferation and migration in CRC through regulation of miR-1229/BCL2L10 axis, which suggested that circTADA2A might represent a novel potential target for the treatment of CRC.



中文翻译：

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circTADA2A 通过调节 miR-1229/BCL2L10 信号轴延缓结直肠癌的进展

背景：结直肠癌（CRC）是全球癌症相关死亡的主要原因之一，已成为严重的公共卫生问题。越来越多的证据证明，circRNA 在 CRC 的发生和发展中是关键的调节剂。尽管 circTADA2A 在骨肉瘤和乳​​腺癌中的作用已被探索，但 circTADA2A 在 CRC 中的具体作用仍然未知。
方法：基于 GEO 数据集的生物信息学分析用于评估 CRC 中失调的 circRNA。CCK-8和transwell检测用于检测CRC细胞的功能。进行 qRT-PCR 和蛋白质印迹以评估 RNA 和蛋白质的表达。进行荧光素酶测定和RNA下拉实验以验证miR与其靶标之间的相互作用。
结果：与正常样本相比，CRC 组织中的 CircTADA2A 下调。当暴露于 RNase R 和放线菌素 D 处理时，CircTADA2A 表现出比其线性形式更大的稳定性。qRT-PCR 分析验证了 CRC 中 circTADA2A 的较低表达水平。功能丧失和功能获得测定表明，circTADA2A 在 CRC 细胞增殖和迁移中发挥抑制作用。从机制上讲，circTADA2A 充当 miR-1229 的海绵。进一步的实验表明，circTADA2A 通过与 miR-1229 竞争性结合来调节 BCL2L10 的表达。更重要的是，circTADA2A在CRC细胞恶性行为中的抑癌作用是由BCL2L10介导的。
结论：circTADA2A 通过调节 miR-1229/BCL2L10 轴抑制 CRC 中的细胞增殖和迁移，这表明 circTADA2A 可能代表治疗 CRC 的新潜在靶点。