Hsa_circ_0101308 adjusted by N6-methyladenosine (m6A) impacts chemo-resistance in cervical cancer via sponging miR-224.

Abstract

BackgroundConsidering the significance of circRNA-miRNA network underlying cervical cancer (CC) development, this investigation was devised to explore whether and how 6-methyladinosinek (m⁶A)-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 m⁶A-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 (P < 0.05). Hsa_circ_0101308 sponed miR-224 and suppressed its expression in HeLa cell line (P < 0.05), and either under-expressed m⁶A-adjusted hsa_circ_0101308 or over-expressed miR-224 strengthened viability of HeLa, HeLa/DDP, HeLa/ADM and HeLa/TAX cell lines (P < 0.05). Additionally, miR-224 targeted CADM1 and down-regulated its mRNA level (P < 0.05), which influenced p-PI3K/PI3K or p-Akt/Akt ratio (P < 0.05).ConclusionThe network combined by m⁶A-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.