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环状 RNA TP53 通过作为 miR-876-3p 的海绵来增加周期蛋白依赖性激酶样 3 的表达,从而促进结直肠癌的发生。

CircTP53 promotes colorectal cancer by acting as a miR-876-3p sponge to increase cyclin-dependent kinase-like 3 expression.

机构信息

College of Basic Medicine, The Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China.

Departments of General Surgery, The Affliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China.

出版信息

Cell Signal. 2021 Feb;78:109845. doi: 10.1016/j.cellsig.2020.109845. Epub 2020 Nov 21.

Abstract

According to ceRNA theory, circular RNAs could regulate certain protein expression through targeting corresponding microRNAs to affect the progression of multiple diseases, including colorectal cancer. CircTP53 (hsa_circ_0107702), highly expressed in thyroid cancer tissues, could promote the proliferation of thyroid cancer. However, the function of circTP53 in colorectal cancer is still unclear. In our study, we found circTP53 was significantly up-regulated in colorectal cancer tissues from patients and in colorectal cell lines. Next, using colorectal cell lines, we confirmed that circTP53 promoted the proliferation, migration and invasion, and reduced the apoptotic rate. Furthermore, through bioinformatics analysis and experimental confirmation, we found circTP53 functioned as the sponge of miR-876-3p, and miR-876-3p reversed the phenotype of circTP53 on the facilitation of colorectal cancer. Additionally, we found circTP53 promoted the progression of colorectal cancer by elevating the expression of CDKL3. At last, we suggested that circTP53 knockdown could inhibit colorectal cancer progression in vivo. In conclusion, circTP53 was highly expressed in colorectal cancer tissues, and promoted colorectal cancer progression via modulating miR-876-3p/CDKL3 axis.

摘要

根据 ceRNA 理论,环状 RNA 可以通过靶向相应的 microRNA 来调节某些蛋白质的表达,从而影响包括结直肠癌在内的多种疾病的进展。CircTP53(hsa_circ_0107702)在甲状腺癌组织中高表达,可促进甲状腺癌细胞的增殖。然而,circTP53 在结直肠癌中的功能尚不清楚。在我们的研究中,我们发现 circTP53 在患者的结直肠癌组织和结直肠细胞系中显著上调。接下来,我们使用结直肠细胞系证实 circTP53 促进了增殖、迁移和侵袭,并降低了细胞凋亡率。此外,通过生物信息学分析和实验验证,我们发现 circTP53 作为 miR-876-3p 的海绵发挥作用,而 miR-876-3p 逆转了 circTP53 对促进结直肠癌的表型。此外,我们发现 circTP53 通过上调 CDKL3 的表达促进了结直肠癌的进展。最后,我们提出 circTP53 的敲低可以抑制体内结直肠癌的进展。总之,circTP53 在结直肠癌组织中高表达,并通过调节 miR-876-3p/CDKL3 轴促进结直肠癌的进展。

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