Tang Yan, Zhou Lei, Liu Lili
Department of Gynecology and Obstetrics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou City, Liaoning Province, PR China.
Allergy and Clinical Immunology Research Centre, First Affiliated Hospital of Jinzhou Medical University, Jinzhou City, Liaoning Province, PR China.
Histol Histopathol. 2023 May;38(5):571-584. doi: 10.14670/HH-18-541. Epub 2022 Oct 27.
Circular RNAs (circRNAs) play crucial regulatory roles in cancer progression and the development of radio-resistance. Here, we intended to explore the role of circ_0085616 in cervical cancer progression and its associated mechanism.
Colony formation assay was employed to analyze the radio-resistance and proliferation of cervical cancer cells. Cell proliferation ability was also assessed by 5-ethynyl-2'-deoxyuridine (EdU) assay. Cell apoptosis was analyzed by flow cytometry. Tube formation assay was performed to analyze cell angiogenesis ability. Transwell assays were conducted to measure cell migration and invasion abilities. Dual-luciferase reporter assay was utilized to verify the target relationships. Xenograft mice model was used to analyze the role of circ_0085616 in tumor growth in vivo.
Circ_0085616 expression was elevated in cervical cancer tissues and cell lines. Circ_0085616 interference suppressed the radio-resistance, proliferation, tube formation, migration, and invasion and elevated the apoptosis rate of cervical cancer cells. Circ_0085616 acted as a sponge for microRNA-541-3p (miR-541-3p), and miR-541-3p was negatively regulated by circ_0085616 in cervical cancer cells. Circ_0085616 absence-induced changes in the behaviors of cervical cancer cells were largely overturned by anti-miR-541-3p. miR-541-3p negatively regulated ADP ribosylation factor like GTPase 2 (ARL2) expression by binding to its 3' untranslated region (3'UTR). miR-541-3p mimic-induced effects were largely reversed by pcDNA-ARL2 in cervical cancer cells. Circ_0085616 positively regulated ARL2 expression by sequestering miR-541-3p. Circ_0085616 absence significantly inhibited the tumor growth in vivo.
Circ_0085616 contributed to the radio-resistance and progression of cervical cancer partly through mediating the miR-541-3p/ARL2 axis.
环状RNA（circRNAs）在癌症进展和放射抗性发展中发挥关键调节作用。在此，我们旨在探讨circ_0085616在宫颈癌进展中的作用及其相关机制。
采用集落形成试验分析宫颈癌细胞的放射抗性和增殖能力。细胞增殖能力也通过5-乙炔基-2'-脱氧尿苷（EdU）试验进行评估。通过流式细胞术分析细胞凋亡。进行管形成试验以分析细胞血管生成能力。采用Transwell试验测量细胞迁移和侵袭能力。利用双荧光素酶报告基因试验验证靶标关系。使用异种移植小鼠模型分析circ_0085616在体内肿瘤生长中的作用。
circ_0085616在宫颈癌组织和细胞系中表达升高。circ_0085616干扰抑制了宫颈癌细胞的放射抗性、增殖、管形成、迁移和侵袭，并提高了细胞凋亡率。circ_0085616作为微小RNA-541-3p（miR-541-3p）的海绵，在宫颈癌细胞中circ_0085616对miR-541-3p起负调节作用。circ_0085616缺失诱导的宫颈癌细胞行为变化在很大程度上被抗miR-541-3p所逆转。miR-541-3p通过与其3'非翻译区（3'UTR）结合对ADP核糖基化因子样GTP酶2（ARL2）表达起负调节作用。在宫颈癌细胞中，pcDNA-ARL2在很大程度上逆转了miR-541-3p模拟物诱导的效应。circ_0085616通过隔离miR-541-3p对ARL2表达起正调节作用。circ_0085616缺失显著抑制了体内肿瘤生长。
circ_0085616部分通过介导miR-541-3p/ARL2轴促进宫颈癌的放射抗性和进展。
