Hsa_circ_0101308 adjusted by N6-methyladenosine (m 6 A) impacts chemo-resistance in cervical cancer via sponging miR-224
Background
Considering the significance of circRNA-miRNA network underlying cervical cancer (CC) development, this investigation was devised to explore whether and how 6-methyladinosinek (m 6 A)-adjusted hsa_circ_0101308/miR-224 axis participated in altering chemo-resistance in CC.
Methods
Forty-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 m 6 A-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.
Results
Hsa_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 m 6 A-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).
Conclusion
The network combined by m 6 A-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.