环状 RNA AGFG1 通过调节 YY1/CTNNB1 促进结直肠癌转移和干性。
CircAGFG1 drives metastasis and stemness in colorectal cancer by modulating YY1/CTNNB1.
机构信息
School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou, 310023, Zhejiang, China.
Department of Neurosurgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China.
出版信息
Cell Death Dis. 2020 Jul 17;11(7):542. doi: 10.1038/s41419-020-2707-6.
Colorectal cancer (CRC) is a common malignancy with high occurrence and mortality worldwide. In recent years, the overall survival rate of CRC patients has been improved because of the advances in early diagnosis and therapy. However, the prognosis of CRC patients at the advanced stage is still poor due to high recurrence rate and metastasis. The function of circular RNA (circRNA) ArfGAP with FG repeats 1 (circAGFG1) has been explored in non-small-cell lung cancer and triple-negative breast cancer. Nevertheless, its role in CRC is not clear. In this study, circAGFG1 was upregulated in CRC cell lines. CircAGFG1 silencing significantly suppressed cell proliferation, migration, invasion, and stemness, while promoted cell apoptosis in CRC. Meanwhile, we found that circAGFG1 also accelerated CRC tumor growth and metastasis in vivo. Importantly, circAGFG1 activated Wnt/β-catenin pathway through regulating CTNNB1. Afterwards, YY1 was found to transcriptionally activate CTNNB1. Furthermore, circAGFG1 directly sponged miR-4262 and miR-185-5p to upregulate YY1 expression. Eventually, rescue assays demonstrated that the effect of circAGFG1 silencing on CRC cell functions was observably reversed by upregulating YY1 or CTNNB1. In brief, our findings uncovered that circAGFG1 modulated YY1/CTNNB1 axis to drive metastasis and stemness in CRC by sponging miR-4262 and miR-185-5p.
结直肠癌(CRC)是一种常见的恶性肿瘤,全球发病率和死亡率均较高。近年来,由于早期诊断和治疗的进展,CRC 患者的总体生存率有所提高。然而,由于高复发率和转移率,CRC 晚期患者的预后仍然较差。环状 RNA(circRNA)ArfGAP 与 FG 重复 1(circAGFG1)在非小细胞肺癌和三阴性乳腺癌中的作用已经得到了探索。然而,其在 CRC 中的作用尚不清楚。在本研究中,CRC 细胞系中 circAGFG1 上调。circAGFG1 沉默显著抑制 CRC 细胞的增殖、迁移、侵袭和干性,同时促进细胞凋亡。同时,我们发现 circAGFG1 还能在体内加速 CRC 肿瘤的生长和转移。重要的是,circAGFG1 通过调节 CTNNB1 激活 Wnt/β-catenin 通路。随后,发现 YY1 转录激活 CTNNB1。此外,circAGFG1 直接吸附 miR-4262 和 miR-185-5p 来上调 YY1 表达。最终,挽救实验表明,circAGFG1 沉默对 CRC 细胞功能的影响可以通过上调 YY1 或 CTNNB1 而明显逆转。总之,我们的研究结果揭示了 circAGFG1 通过吸附 miR-4262 和 miR-185-5p 来调节 YY1/CTNNB1 轴,从而驱动 CRC 的转移和干性。
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