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Hsa_circ_0087862/miR-149-5p/TRAF6调控轴在结直肠癌进展中的作用

The Role of Hsa_circ_0087862/miR-149-5p/TRAF6 Regulatory Axis in Colorectal Cancer Progression.

作者信息

Xu Qiu, Xu Yi, Yang Tianyao, Tang Yan, Yang Qiong

机构信息

Department of Thyroid and Breast Surgery, Nanyang First People's Hospital, Nanyang, 473004, China.

Nanyang Key Laboratory of Thyroid Tumor Prevention and Treatment, Nanyang First People's Hospital, Nanyang, 473004, China.

出版信息

Appl Biochem Biotechnol. 2025 May 14. doi: 10.1007/s12010-025-05283-4.

DOI:10.1007/s12010-025-05283-4
PMID:40366539
Abstract

Circular RNAs (circRNAs) have been reported to be associated with the progression of various tumors including colorectal cancer (CRC). However, the role and underlying mechanism of hsa_circ_0087862 in CRC remains unclear. Hsa_circ_0087862 expression in CRC tissues was analyzed using two GEO datasets (GSE138589 and GSE126094). Expression of hsa_circ_0087862, miR-149-5p and tumor necrosis factor receptor-associated factor 6 (TRAF6) in CRC cells was detected. The subcellular distribution of hsa_circ_0087862 was analyzed using a Cytoplasmic & Nuclear RNA Purification Kit. The function of hsa_circ_0087862 in CRC cells was detected using CCK-8, Transwell invasion assay, flow cytometry analysis, and Caspase-3 activity assay. The relationships between hsa_circ_0087862, miR-149-5p and TRAF6 were detected using luciferase reporter assay, RIP, or biotinylated RNA pull-down assay. Hsa_circ_0087862 was upregulated in CRC tissues and cells. Hsa_circ_0087862 is resistant to RNase R digestion and predominantly localized in the cytoplasm. Interference with hsa_circ_0087862 inhibited the malignant phenotypes of CRC cells by reducing cell proliferation and invasive abilities and triggering apoptosis. Hsa_circ_0087862 silencing inhibited TRAF6 expression by sponging miR-149-5p in CRC cells. Inhibition of miR-149-5p attenuated the effects of hsa_circ_0087862 on the malignant phenotypes of CRC cells. TRAF6 overexpression abolished the effects of miR-149-5p on cell growth, invasion and apoptosis in CRC cells. In conclusion, hsa_circ_0087862 silencing inhibited the malignant behaviors of CRC cells through inhibiting TRAF6 expression by sponging miR-149-5p.

摘要

据报道,环状RNA(circRNAs)与包括结直肠癌(CRC)在内的多种肿瘤进展相关。然而,hsa_circ_0087862在CRC中的作用及潜在机制仍不清楚。利用两个基因表达综合数据库(GSE138589和GSE126094)分析了hsa_circ_0087862在CRC组织中的表达。检测了CRC细胞中hsa_circ_0087862、miR-149-5p和肿瘤坏死因子受体相关因子6(TRAF6)的表达。使用细胞质和细胞核RNA纯化试剂盒分析hsa_circ_0087862的亚细胞分布。使用CCK-8、Transwell侵袭试验、流式细胞术分析和Caspase-3活性试验检测hsa_circ_0087862在CRC细胞中的功能。使用荧光素酶报告基因试验、RNA免疫沉淀(RIP)或生物素化RNA下拉试验检测hsa_circ_0087862、miR-149-5p和TRAF6之间的关系。hsa_circ_0087862在CRC组织和细胞中上调。hsa_circ_0087862对核糖核酸酶R消化具有抗性,主要定位于细胞质中。干扰hsa_circ_0087862可通过降低细胞增殖和侵袭能力并触发凋亡来抑制CRC细胞的恶性表型。在CRC细胞中,hsa_circ_0087862沉默通过海绵化miR-149-5p抑制TRAF6表达。抑制miR-149-5p可减弱hsa_circ_0087862对CRC细胞恶性表型的影响。TRAF6过表达消除了miR-149-5p对CRC细胞生长、侵袭和凋亡的影响。总之,hsa_circ_0087862沉默通过海绵化miR-149-5p抑制TRAF6表达,从而抑制CRC细胞的恶性行为。

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