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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2024

Open Access 01-12-2024 | Research

The epigenetic downregulation of LncGHRLOS mediated by RNA m6A methylase ZCCHC4 promotes colorectal cancer tumorigenesis

Authors: Ke Chen, Jingcheng Zhang, Lei Meng, Lingshang Kong, Ming Lu, Zhengguang Wang, Wenbin Wang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2024

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Abstract

Background

m6A modification is currently recognized as a major driver of RNA function that maintains cancer cell homeostasis. Long non-coding (Lnc) RNAs control cell proliferation and play an important role in the occurrence and progression of colorectal cancer (CRC). ZCCHC4 is a newly discovered m6A methyltransferase whose role and mechanism in tumors have not yet been elucidated.

Methods

The EpiQuik m6A RNA methylation kit was used to detect the level of total RNA m6A in six types of digestive tract tumors. The Kaplan-Meier method and receiver operating characteristic curve were used to evaluate the prognostic and diagnostic value of the newly discovered m6A methyltransferase, ZCCHC4, in CRC. The effects on CRC growth in vitro and in vivo were studied using gain- and loss-of-function experiments. The epigenetic mechanisms underlying ZCCHC4 upregulation in CRC were studied using RIP, MeRIP-seq, RNA pull-down, and animal experiments.

Results

We reported that the ZCCHC4-LncRNAGHRLOS-KDM5D axis regulates the growth of CRC in vitro and in vivo. We found that ZCCHC4 was upregulated in primary CRC samples and could predict adverse clinical outcomes in patients with CRC. Mechanistically, ZCCHC4 downregulated LncRNAGHRLOS to promote CRC tumorigenesis. As a downstream molecule of LncRNAGHRLOS, KDM5D directly controls CRC cell proliferation, migration, and invasion.

Conclusion

This study suggests that the ZCCHC4 axis contributes to the tumorigenesis and progression of CRC and that ZCCHC4 may be a potential biomarker for this malignancy.
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Metadata
Title
The epigenetic downregulation of LncGHRLOS mediated by RNA m6A methylase ZCCHC4 promotes colorectal cancer tumorigenesis
Authors
Ke Chen
Jingcheng Zhang
Lei Meng
Lingshang Kong
Ming Lu
Zhengguang Wang
Wenbin Wang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2024
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-024-02965-5

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