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 (mA) in many cells. However, the significance of mA-modified circular RNAs (circRNAs) has not been elucidated in HGSOC peritoneal metastasis. Here, we aimed to investigate the participation and potential functions of mA-modified circRNAs in HGSCO peritoneal metastasis.

METHODS

Cancerous tissues were collected from the and the peritoneal metastasis lesions of HGSCO patients. MA-tagged circRNAs were identified by mA-modified RNA immunoprecipitation sequencing (mA-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 mA-modified circRNAs.

RESULTS

For the mA-modified circRNAs, 259 were upregulated and 227 were downregulated in the peritoneal metastasis than in the situ lesions of HGSCO patients. For the mA peaks, 1541 were upregulated and 1293 were downregulated in the peritoneal metastasis than in the 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 lesions of HGSCO patients. The upregulated mA-modified circRNAs were associated with the HIF-1 signaling. The downregulated mA-modified circRNAs were associated with the MAPK signaling.

CONCLUSIONS

This work firstly identified the transcriptome-wide map of mA-modified circRNAs in peritoneal metastasis of HGSCO. Our findings provided novel evidences about the participation of mA-modified circRNAs HIF-1 and MAPK signaling and a new insight in molecular target of HGSCO peritoneal metastasis.