Gao Qizhong, Cheng Xiaowei, Gao Xiang
Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
Internal Medicine Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
Physiol Rep. 2024 Nov;12(23):e70137. doi: 10.14814/phy2.70137.
Circular RNAs have been implicated as critical regulators in the initiation and progression of colorectal cancer (CRC). This study was intended to elucidate the functional significance of the circ_0089761/miR-27b-3p/programmed cell death ligand 1 (PD-L1) axis in CRC. Our findings indicated that circ_0089761 expression was significantly elevated in CRC tissues and cell lines. Furthermore, the high expression of circ_0089761 was correlated with TNM stage and tumor size. Silencing circ_0089761 inhibited CRC cell proliferation, migration, and invasion, and increased apoptosis. Mechanistically, circ_0089761 facilitated its biological function by binding to miR-27b-3p to upregulate PD-L1 expression in CRC. Coculture experiments confirmed that low expression of circ_0089761 impeded CD8 + T cell apoptosis and depletion, activated CD8 + T cell function, and increased secretion of the immune effector cytokines IFN-γ, TNF-α, perforin, and granzyme-B. MiR-27b-3p inhibition or PD-L1 overexpression partially impeded CD8 + T cell function. The circ_0089761/miR-27b-3p/PD-L1 axis is postulated to exert pivotal functions in the mechanistic progression of CRC. Furthermore, it holds promising prospects as a feasible biomarker and therapeutic target for CRC.
环状RNA已被认为是结直肠癌（CRC）起始和进展中的关键调节因子。本研究旨在阐明circ_0089761/miR-27b-3p/程序性细胞死亡配体1（PD-L1）轴在CRC中的功能意义。我们的研究结果表明，circ_0089761在CRC组织和细胞系中的表达显著升高。此外，circ_0089761的高表达与TNM分期和肿瘤大小相关。沉默circ_0089761可抑制CRC细胞的增殖、迁移和侵袭，并增加细胞凋亡。机制上，circ_0089761通过与miR-27b-3p结合来上调CRC中PD-L1的表达，从而促进其生物学功能。共培养实验证实，circ_0089761的低表达可阻碍CD8 + T细胞的凋亡和耗竭，激活CD8 + T细胞功能，并增加免疫效应细胞因子IFN-γ、TNF-α、穿孔素和颗粒酶B的分泌。抑制miR-27b-3p或过表达PD-L1可部分阻碍CD8 + T细胞功能。推测circ_0089761/miR-27b-3p/PD-L1轴在CRC的机制进展中发挥关键作用。此外，它作为CRC的可行生物标志物和治疗靶点具有广阔的前景。
