Comprehensive analysis of m6A-modified circRNAs in peritoneal metastasis of high grade serious carcinoma of ovary

PURPOSE: High-grade serous ovarian cancer (HGSOC) remains the most lethal female cancer due to metastasis. CircRNAs are recently identified to be modified by N6-methyladenosine (m(6)A) in many cells. However, the significance of m(6)A-modified circular RNAs (circRNAs) has not been elucidated in HGSOC peritoneal metastasis. Here, we aimed to investigate the participation and potential functions of m(6)A-modified circRNAs in HGSCO peritoneal metastasis. METHODS: Cancerous tissues were collected from the in situ and the peritoneal metastasis lesions of HGSCO patients. M(6)A-tagged circRNAs were identified by m(6)A-modified RNA immunoprecipitation sequencing (m(6)A-RIP-seq). Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the potential functions of the m(6)A-modified circRNAs. RESULTS: For the m(6)A-modified circRNAs, 259 were upregulated and 227 were downregulated in the peritoneal metastasis than in the situ lesions of HGSCO patients. For the m(6)A peaks, 1541 were upregulated and 1293 were downregulated in the peritoneal metastasis than in the in situ lesions of HGSCO patients. For the differential expressed circRNAs, 1911(19.6%) were upregulated and 2883(29.6%) were downregulated in the peritoneal metastasis than in the in situ lesions of HGSCO patients. The upregulated m(6)A-modified circRNAs were associated with the HIF-1 signaling. The downregulated m(6)A-modified circRNAs were associated with the MAPK signaling. CONCLUSIONS: This work firstly identified the transcriptome-wide map of m(6)A-modified circRNAs in peritoneal metastasis of HGSCO. Our findings provided novel evidences about the participation of m(6)A-modified circRNAs via HIF-1 and MAPK signaling and a new insight in molecular target of HGSCO peritoneal metastasis.