Hypoxia regulates tumour characteristic RNA modifications in ovarian cancers

Abstract

Analysis of ovarian cancer tissue and normal ovarian tissue revealed 31 RNA modifications with significant differences observed in cancer tissue compared with normal tissue. Moreover, we found Im and chm5U as characteristic RNA modifications in advanced and platinum‐resistant ovarian cancers, respectively. Considering that these differences in RNA modifications may be due to the intra‐tumour microenvironment, we xenografted the ovarian cancer cell line RMG‐1 to create RMG‐1 tumours and compared them with original RMG‐1 cells. As a result, 14 of the 31 RNA modifications showed marked variations during tumorigenesis. Eight RNA modifications (m2,2G, t6A, m7G, m5U, m1G, i6A, m6t6A and m1A), which were upregulated in ovarian cancer tissues and in RMG‐1‐xenografted tumour, were also upregulated under hypoxic conditions. RNAseq analysis, using the matched RNA samples analysed for RNA modifications, showed that 2137 genes were highly expressed in ovarian cancer tissues compared with those in normal ovarian tissues. Of these, 134 genes, which were enriched in a gene set belonging to the hypoxia signalling pathway, were positively correlated with the above eight RNA modifications. These results suggest that the tumour microenvironment, including hypoxia, is important for cancer characteristic RNA modifications.

Insights into the regulatory role of RNA methylation modifications in glioma

“…M7G Currently, METTL1 is the most well-recognized m7G regulator, which binds with its cofactor, WD repeat domain 4 (WDR4), to catalyze m7G modifications in tRNA, miRNA, and mRNA [134]. m7G has a pivotal role in several types of tumors, including gliomas, ovarian cancers, certain sarcomas, breast cancers and so on [9,[135][136][137]. Li et al [138] found that METTL1 may promote the malignant behavior of glioma cells through the MAPK signaling pathway.…”