Yan Kun, Hu Chunyan, Cheng Yali, Zheng Lingzhi, Zeng Baojin, Zhao Sujun, Liu Chen
Department of Gynecology, Northwest Women's and Children's Hospital, Xi'an, 710016, China.
Department of Gynecology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Enze Hospital, Taizhou Enze Medical Center (Group), No. 1, Tongyang Road, Luqiao District, Taizhou, 318050, China.
Discov Oncol. 2024 Mar 27;15(1):88. doi: 10.1007/s12672-024-00933-1.
Deregulation of circular RNAs (circRNAs) is widely recognized in cancer progression. Our study aims to investigate the role of circ_0020460 in the development of cervical cancer (CC) and its potential mechanism of action. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays were used to detect the expression levels of circ_0020460, miR-485-3p and C-X-C motif chemokine ligand 1 (CXCL1). The roles of circ_0020460 on cell proliferation, cell migration, cell invasion, cell apoptosis, and angiogenesis were investigated using cell counting kit-8 (CCK-8) and Ethynyl deoxyuridine (Edu) assay, wound healing assay, transwell assay, flow cytometry assay, and tube formation assay, respectively. The putative relationship predicted by bioinformatics analysis was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft models were constructed to explore the role of circ_0020460 in vivo. The expression of circ_0020460 and CXCL1 expression were increased, while miR-485-3p expression was declined in CC tissues and cells. Circ_0020460 knockdown suppressed CC cell proliferation, cell migration, cell invasion, angiogenesis, and promoted cell apoptosis. Circ_0020460 functioned as a miR-485-3p sponge to inhibit miR-485-3p level, and the anti-cancer effects mediated by circ_0020460 knockdown were reversed by miR-485-3p inhibitor. MiR-485-3p bound to CXCL1 3' untranslated region (3'UTR) to degrade CXCL1 expression, and the anti-cancer effects of miR-485-3p restoration were impaired by CXCL1 overexpression. Circ_0020460 downregulation inhibited CC xenograft tumor growth. These results suggest that circ_0020460 promoted the malignant behavior of CC cells by modulating the miR-485-3p/CXCL1 axis.
环状RNA（circRNAs）的失调在癌症进展中已得到广泛认可。我们的研究旨在探讨circ_0020460在宫颈癌（CC）发生发展中的作用及其潜在作用机制。采用定量实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测circ_0020460、miR-485-3p和C-X-C基序趋化因子配体1（CXCL1）的表达水平。分别使用细胞计数试剂盒-8（CCK-8）和乙炔基脱氧尿苷（Edu）检测法、伤口愈合检测法、Transwell检测法、流式细胞术检测法和管腔形成检测法，研究circ_0020460对细胞增殖、细胞迁移、细胞侵袭、细胞凋亡和血管生成的作用。通过双荧光素酶报告基因检测法和RNA免疫沉淀（RIP）检测法验证了生物信息学分析预测的假定关系。构建异种移植模型以探究circ_0020460在体内的作用。在CC组织和细胞中，circ_0020460和CXCL水平升高，而miR-485-3p表达下降。敲低circ_0020460可抑制CC细胞增殖、迁移、侵袭和血管生成，并促进细胞凋亡。Circ_0020460作为miR-485-3p的海绵，抑制miR-485-3p水平，而miR-485-3p抑制剂可逆转circ_0020460敲低介导的抗癌作用。MiR-485-3p与CXCL1 3'非翻译区（3'UTR）结合，降低CXCL1表达，而CXCL1过表达则削弱了miR-485-3p恢复后的抗癌作用。下调circ_0020460可抑制CC异种移植瘤的生长。这些结果表明，circ_0020460通过调节miR-485-3p/CXCL1轴促进CC细胞的恶性行为。
