Department of Gastrointestinal Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Department of Colorectal Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Cell Cycle. 2023 Jul-Aug;22(14-16):1743-1758. doi: 10.1080/15384101.2023.2225923. Epub 2023 Jul 9.
Colorectal cancer (CRC) is a prevalent gastrointestinal tumor globally. Circular RNAs (circRNAs) have been identified as regulatory players in the pathogenesis of CRC. However, it is unclear whether hsa_circ_0050102 (circPGPEP1) affects the malignant progression and immune escape in CRC.
Bioinformatics analysis and circRNA in vivo precipitation experiments were performed to analyze and identify circRNAs that mediate immune escape in CRC. Using luciferase reporter assay, RIP, RNA pull-down assay, and FISH, the interaction between circPGPEP1, miR-515-5p, and nuclear factor of activated T-cell 5 (NFAT5) was identified. The functional role of circPGPEP1/miR-515-5p/NFAT5 axis in CRC anti-tumor immunity was investigated by co-culture assay, CFSE assay, and flow cytometry of CRC cells and T cells.
circPGPEP1 was a stable circRNA that was highly expressed in CRC. Functionally, circPGPEP1 silencing not only effectively inhibited CRC cell proliferation, migration, EMT, and immune escape and promoted apoptosis in vitro, but also inhibited CRC tumor growth and immune escape in vivo. In terms of the regulatory mechanism, circIGF2BP3 competitively upregulated NFAT5 expression by sponging miR-515-5p. Furthermore, functional rescue experiments showed that circPGPEP1 acted in CRC by regulating the miR-515-5p/NFAT5 axis.
Collectively, circPGPEP1 exerts an oncogene role in CRC by regulating the miR-515-5p/NFAT5 axis.
结直肠癌（CRC）是全球普遍存在的胃肠道肿瘤。环状 RNA（circRNAs）已被确定为 CRC 发病机制中的调节因子。然而，hsa_circ_0050102（circPGPEP1）是否影响 CRC 的恶性进展和免疫逃逸尚不清楚。
通过生物信息学分析和 circRNA 体内沉淀实验，分析和鉴定介导 CRC 免疫逃逸的 circRNAs。利用荧光素酶报告基因检测、RIP、RNA 下拉实验和 FISH 实验，鉴定 circPGPEP1 与 miR-515-5p 和激活 T 细胞核因子 5（NFAT5）之间的相互作用。通过共培养实验、CFSE 实验和 CRC 细胞和 T 细胞的流式细胞术，研究 circPGPEP1/miR-515-5p/NFAT5 轴在 CRC 抗肿瘤免疫中的功能作用。
circPGPEP1 是一种稳定的 circRNA，在 CRC 中高度表达。功能上，circPGPEP1 沉默不仅能有效抑制 CRC 细胞的增殖、迁移、上皮间质转化和免疫逃逸，还能促进体外细胞凋亡，并能抑制体内 CRC 肿瘤生长和免疫逃逸。在调控机制方面，circIGF2BP3 通过海绵吸附 miR-515-5p 竞争性地上调 NFAT5 的表达。此外，功能恢复实验表明，circPGPEP1 通过调节 miR-515-5p/NFAT5 轴在 CRC 中发挥作用。
总之，circPGPEP1 通过调节 miR-515-5p/NFAT5 轴在 CRC 中发挥致癌作用。
