研究动态
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CircZFR 通过稳定 BCLAF1 和调节 miR-3127-5p/RTKN2 轴促进结直肠癌进展。

CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis.

发表日期:2024 May 24
作者: Jiaxin Chen, Huijuan Wang, Jianbin Xu, Engeng Chen, Qing Meng, Jiawei Wang, Haoyi Xiang, Wei Zhou, Ge Shan, Zhenyu Ju, Zhangfa Song
来源: Disease Models & Mechanisms

摘要:

环状 RNA (circRNA) 的异常表达通常与结直肠癌 (CRC) 有关。在这里,我们确定 circZFR 是一种有前途的 CRC 诊断和预后生物标志物。 CircZFR 在 CRC 组织和血清外泌体中表达上调,其水平与癌症发病率、晚期阶段和转移有关。在体外和体内环境中,circZFR 促进了 CRC 的生长和扩散,同时抑制了细胞凋亡。 circZFR过表达的外泌体促进共培养的CRC细胞的增殖和迁移。从机制上讲,CRC 细胞中的上皮剪接调节蛋白 1 (ESRP1) 可能会增强 circZFR 的产生。 BCL2 相关转录因子 1 (BCLAF1) 与 circZFR 结合,从而阻止其泛素化降解。此外,circZFR 吸收 miR-3127-5p 来增强 rhotekin 2 (RTKN2) 的表达。我们的 TCP1-CD-QDs 纳米载体能够携带并递送 circZFR siRNA (si-circZFR) 至 CRC 组织和细胞的脉管系统,从而抑制患者来源的异种移植 (PDX) 模型中肿瘤的生长。综上所述,我们的结果表明,circZFR 是一种致癌 circRNA,它以 BCLAF1 和 miR-3127-5p 依赖性方式促进 CRC 的发展和传播。 CircZFR 是一种可能的用于诊断的血清活检标志物,也是进一步治疗 CRC 的理想靶标。© 2024。中国科学出版社。
Aberrant expression of circular RNAs (circRNAs) is frequently linked to colorectal cancer (CRC). Here, we identified circZFR as a promising biomarker for CRC diagnosis and prognosis. CircZFR was upregulated in CRC tissues and serum exosomes and its level was linked to cancer incidence, advanced-stages, and metastasis. In both in vitro and in vivo settings, circZFR promoted the growth and spread while suppressing apoptosis of CRC. Exosomes with circZFR overexpression promoted the proliferation and migration of cocultured CRC cells. Mechanistically, epithelial splicing regulatory protein 1 (ESRP1) in CRC cells may enhance the production of circZFR. BCL2-associated transcription factor 1 (BCLAF1) bound to circZFR, which prevented its ubiquitinated degradation. Additionally, circZFR sponged miR-3127-5p to boost rhotekin 2 (RTKN2) expression. Our TCP1-CD-QDs nanocarrier was able to carry and deliver circZFR siRNA (si-circZFR) to the vasculature of CRC tissues and cells, which inhibited the growth of tumors in patient-derived xenograft (PDX) models. Taken together, our results show that circZFR is an oncogenic circRNA, which promotes the development and spread of CRC in a BCLAF1 and miR-3127-5p-dependent manner. CircZFR is a possible serum biopsy marker for the diagnosis and a desirable target for further treatment of CRC.© 2024. Science China Press.