Abnormal 5-methylcytosine lncRNA methylome is involved in human high-grade serous ovarian cancer

Am J Transl Res. 2021 Dec 15;13(12):13625-13639. eCollection 2021.

Abstract

Methylcytosine (m5C) is an important posttranscriptional RNA methylation modification. Studies have reported that aberrant RNA methylation can regulate tumorigenesis and development, indicating the importance of exploring the distribution and biological functions of m5C modification in human high-grade serous ovarian cancer (HGSOC) lncRNAs. In the current study, we identified 2,050 dysregulated m5C peaks, 1,767 of which were significantly upregulated, while 283 were significantly downregulated by performing methylated RNA immunoprecipitation sequencing on 3 pairs of human HGSOC tissues and paired normal tissues. GO enrichment analysis showed that genes altered by the m5C peak played a key role in phylogeny, protein metabolism, and gene mismatch repair. KEGG pathway analysis revealed that these genes were enriched in some important pathways in cancer regulation, such as the PI3K-Akt signalling pathway, transcriptional dysregulation in cancer, and mismatch repair pathways. In addition, through joint analysis of MeRIP-seq and RNA-seq data, we identified 1671 differentially methylated m5C peaks and synchronous differentially expressed genes. These genes play a key role in cell growth or maintenance, RNA metabolism and material transport. We analyzed expression of the m5C modification regulatory gene collagen type IV alpha 3 chain (COL4A3) in 80 HGSOC tissue samples by immunohistochemistry and found that high expression of COL4A3 was significantly correlated with CA125 level (P=0.016), lymph node metastasis (P<0.001), degree of interstitial invasion (P<0.001) and FIGO staging (P<0.001) and indicated a poorer prognosis. Our results revealed the critical role of m5C methylation of lncRNAs in HGSOC, and provided a reference for the prognostic stratification and treatment strategy of HGSOC.

Keywords: 5-methylcytosine; MeRIP sequencing; high-grade serous cancer; lncRNA; prognosis.