AUTHOR=Guo Lin , Xu Nini , Qiu Daner , Yang Xiaozhe , Zhao Shasha , Zhao Hongxi 

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

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.988578

DOI=10.3389/fonc.2022.988578

ISSN=2234-943X

ABSTRACT=<sec><title>Purpose</title><p>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<sup>6</sup>A) in many cells. However, the significance of m<sup>6</sup>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<sup>6</sup>A-modified circRNAs in HGSCO peritoneal metastasis.</p></sec><sec><title>Methods</title><p>Cancerous tissues were collected from the <italic>in situ</italic> and the peritoneal metastasis lesions of HGSCO patients. M<sup>6</sup>A-tagged circRNAs were identified by m<sup>6</sup>A-modified RNA immunoprecipitation sequencing (m<sup>6</sup>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<sup>6</sup>A-modified circRNAs.</p></sec><sec><title>Results</title><p>For the m<sup>6</sup>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<sup>6</sup>A peaks, 1541 were upregulated and 1293 were downregulated in the peritoneal metastasis than in the <italic>in situ</italic> 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 <italic>in situ</italic> lesions of HGSCO patients. The upregulated m<sup>6</sup>A-modified circRNAs were associated with the HIF-1 signaling. The downregulated m<sup>6</sup>A-modified circRNAs were associated with the MAPK signaling.</p></sec><sec><title>Conclusions</title><p>This work firstly identified the transcriptome-wide map of m<sup>6</sup>A-modified circRNAs in peritoneal metastasis of HGSCO. Our findings provided novel evidences about the participation of m<sup>6</sup>A-modified circRNAs <italic>via</italic> HIF-1 and MAPK signaling and a new insight in molecular target of HGSCO peritoneal metastasis.</p></sec>