Shang Li, Yan Ruchun, Wang Heng, Li Zhuyan
Department of Obstetrics and Gynecology, People's Hospital affiliated to Hubei University of Medicine, Hubei, China.
Department of Dermatology, Taihe Hospital affiliated to Hubei University of Medicine, Hubei, China.
Cancer Biomark. 2025 Jun;42(6):18758592251341157. doi: 10.1177/18758592251341157. Epub 2025 Jun 19.
BackgroundConsidering the significance of circRNA-miRNA network underlying cervical cancer (CC) development, this investigation was devised to explore whether and how 6-methyladinosinek (mA)-adjusted hsa_circ_0101308/miR-224 axis participated in altering chemo-resistance in CC.MethodsForty-nine pairs of CC tissues and para-cancerous normal tissues were gathered, and CC cell lines, comprising HeLa, HeLa/DDP, HeLa/ADM and HeLa/TAX cell lines, were pre-prepared. Expressions of circRNAs, miRNAs and mRNAs were determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and mA-modification of hsa_circ_0101308 was verified based on methylated RNA immunoprecipitation sequencing (MeRIP-Seq) assay. Among CC cell lines, their chemo-resistance was evaluated through CCK8 assay, and their viability was assessed via MTT assay.ResultsHsa_circ_0101308 expression markedly dwindled, accompanied by notably elevated expression of miR-224, within CC tissues, when compared with para-cancerous normal tissues ( < 0.05). Hsa_circ_0101308 sponed miR-224 and suppressed its expression in HeLa cell line ( < 0.05), and either under-expressed mA-adjusted hsa_circ_0101308 or over-expressed miR-224 strengthened viability of HeLa, HeLa/DDP, HeLa/ADM and HeLa/TAX cell lines ( < 0.05). Additionally, miR-224 targeted CADM1 and down-regulated its mRNA level ( < 0.05), which influenced p-PI3K/PI3K or p-Akt/Akt ratio ( < 0.05).ConclusionThe network combined by mA-adjusted hsa_circ_0101308 and miR-224 interfered with chemo-resistance in CC via acting upon CADM1 and PI3K/AKT pathway, which was conducive to optimizing CC treatment.
背景
考虑到环状RNA-微小RNA（circRNA-miRNA）网络在宫颈癌（CC）发生发展中的重要性，本研究旨在探讨6-甲基腺嘌呤（mA）修饰的hsa_circ_0101308/miR-224轴是否以及如何参与改变CC的化疗耐药性。
方法
收集49对CC组织和癌旁正常组织，并预先准备好包括HeLa、HeLa/DDP、HeLa/ADM和HeLa/TAX细胞系在内的CC细胞系。使用定量逆转录-聚合酶链反应（qRT-PCR）测定circRNA、miRNA和mRNA的表达，并基于甲基化RNA免疫沉淀测序（MeRIP-Seq）分析验证hsa_circ_0101308的mA修饰。在CC细胞系中，通过CCK8试验评估其化疗耐药性，并通过MTT试验评估其活力。
结果
与癌旁正常组织相比，CC组织中hsa_circ_0101308表达明显减少，同时miR-224表达显著升高（<0.05）。Hsa_circ_0101308在HeLa细胞系中靶向miR-224并抑制其表达（<0.05），低表达mA修饰的hsa_circ_0101308或过表达miR-224均增强了HeLa、HeLa/DDP、HeLa/ADM和HeLa/TAX细胞系的活力（<0.05）。此外，miR-224靶向细胞粘附分子1（CADM1）并下调其mRNA水平（<0.05），这影响了p-PI3K/PI3K或p-Akt/Akt比值（<0.05）。
结论
由mA修饰的hsa_circ_0101308和miR-224组成的网络通过作用于CADM1和PI3K/AKT途径干扰CC的化疗耐药性，这有助于优化CC的治疗。
