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A pan-cancer analysis of RNASEH1, a potential regulator of the tumor microenvironment

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Abstract

Background

RNASEH1 (Ribonuclease H1) encodes an endonuclease that specifically degrades the RNA of RNA–DNA hybrids and acts in DNA replication and repair. Although there are many studies on RNASEH1, the research of RNASEH1 in cancers is still insufficient. Therefore, in order to clarify the physiological mechanism of RNASEH1 in tumor cells, we evaluated the role of RNASEH1 by combining The Cancer Genome Atlas (TCGA) pan-cancer data and Genotype-Tissue Expression (GTEx) normal tissue data.

Methods

RNASEH1 expression was analyzed by using RNAseq data from TCGA and the GTEx database. The Human Protein Atlas (HPA), GeneCards and STRING database were used to explore the protein information of RNASEH1. The prognostic value of RNASEH1 was analyzed by using the clinical survival data from TCGA. Differential analysis of RNASEH1 in different cancers was performed by using R package “DESeq2”, and enrichment analysis of RNASEH1 was conducted by using R package “clusterProfiler”. We downloaded the immune cell infiltration score of TCGA samples from published articles and online databases, and the correlation analysis between immune cell infiltration levels and RNASEH1 expression was performed. Not only that, we further evaluated the association of RNASEH1 with immune activating genes, immunosuppressive genes, chemokines and chemokine receptors. At the end of the article, the differential expression of RNASEH1 in pan-cancer was validated by using GSE54129, GSE40595, GSE90627, GSE106937, GSE145976 and GSE18672, and qRT-PCR was also performed for verification.

Findings

RNASEH1 was significantly overexpressed in 19 cancers and the overexpression was closely correlated with poor prognosis. Moreover, the expression of RNASEH1 was significantly correlated with the regulation of the tumor microenvironment. In addition, RNASEH1 expression was closely associated with immune cell infiltration, immune checkpoints, immune activators, immunosuppressive factors, chemokines and chemokine receptors. Finally, RNASEH1 also was closely associated with DNA-related physiological activities and mitochondrial-related physiological activities.

Interpretation

Our studying suggests that RNASEH1 is a potential cancer biomarker. And RNASEH1 may be able to regulate the tumor microenvironment by regulating the relevant physiological activities of mitochondrial and thereby regulating the occurrence and development of tumors. Thus, it could be used to develop new-targeted drugs of tumor therapy.

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Data availability

The data used to support this study is available from the corresponding author upon request.

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Acknowledgements

We gratefully acknowledge the financial supports from the PhD fellowship of Nanchang Hangkong University (EA202008259), Natural Science Foundation of Hubei Province (2019CFB391).

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Author notes

  1. Chen Yi and Jun Yang contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Nondestructive Testing, Ministry of Education, Nanchang Hangkong University, Jiangxi, 330063, China

    Chen Yi & Jun Yang

  2. Department of Biomedical Engineering, Nanchang Hangkong University, Jiangxi, 330063, China

    Chen Yi, Jun Yang, Ting Zhang, Shien Xie & Wentao Li

  3. Department of Laboratory Medicine, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, China

    Liu Qin & Dongjuan Chen

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  1. Chen Yi
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Correspondence to Dongjuan Chen.

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The study was approved by the Committee on Human Research of Maternal and Child Health Hospital of Hubei Province (2020IECXM045). All research was performed in accordance with relevant guidelines and regulations.

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Yi, C., Yang, J., Zhang, T. et al. A pan-cancer analysis of RNASEH1, a potential regulator of the tumor microenvironment. Clin Transl Oncol 25, 2569–2586 (2023). https://doi.org/10.1007/s12094-023-03142-4

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