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Updated: Aug 20, 2025

Analysis of Global RNA Synthesis at the Single Cell Level following Hypoxia
Published on: May 13, 2014
Hypoxia regulates tumour characteristic RNA modifications in ovarian cancers
Yuya Monoe1, Shunsuke Miyamoto2,3, Kentaro Jingushi1
1Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
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
Ovarian cancer exhibits distinct RNA modifications, with hypoxia and the tumor microenvironment driving these changes. Understanding these RNA alterations offers new insights into cancer development and potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ovarian cancer tissue shows significant differences in RNA modifications compared to normal tissue.
- Specific RNA modifications, N6-isopentenyladenosine (Im) and 5-hydroxymethyluridine (chm5U), characterize advanced and platinum-resistant ovarian cancers, respectively.
Purpose of the Study:
- To investigate the role of the intra-tumour microenvironment, particularly hypoxia, in driving characteristic RNA modifications in ovarian cancer.
- To identify specific RNA modifications associated with tumorigenesis and their correlation with gene expression pathways.
Main Methods:
- Comparative analysis of RNA modifications in ovarian cancer and normal ovarian tissues.
- Xenograft model using the RMG-1 ovarian cancer cell line to study tumorigenesis.
- RNA sequencing (RNAseq) to analyze gene expression and its correlation with RNA modifications.
- Assessment of RNA modifications under hypoxic conditions.
Main Results:
- 31 RNA modifications differed significantly between ovarian cancer and normal tissues.
- 14 RNA modifications varied during tumorigenesis in the xenograft model.
- Eight specific RNA modifications (m2,2G, t6A, m7G, m5U, m1G, i6A, m6t6A, and m1A) were upregulated in cancer tissues, xenografts, and under hypoxic conditions.
- RNAseq revealed 2137 highly expressed genes in ovarian cancer, with 134 genes enriched in the hypoxia signaling pathway and positively correlated with the eight upregulated RNA modifications.
Conclusions:
- The tumor microenvironment, including hypoxia, significantly influences characteristic RNA modifications in ovarian cancer.
- These findings highlight the importance of hypoxia-driven RNA modifications in ovarian cancer development.
- The identified RNA modifications and associated genes may serve as potential biomarkers or therapeutic targets.
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