Aberrant DNA Methylation Patterns of Deleted in Liver Cancer 1 Isoforms in Hepatocellular Carcinoma
Abstract
Hepatocellular carcinoma (HCC), a common primary liver cancer, is the third leading cause of death worldwide. DNA methylation changes are common in HCC and have been studied to be associated with hepatocarcinogenesis. In our study, we used the MassARRAY® EpiTYPER technology to investigate the methylation differences of deleted in liver cancer 1 (DLC1) (isoform 1 and 3) promoter between HCC tissues and corresponding adjacent noncancerous tissues and the association between methylation levels and clinicopathological features. In addition, the modified CRISPR-Cas9 system and the DNA methyltransferase inhibitor (DNMTi) were utilized to explore the functional correlation of epigenetic modifications and DLC1 gene regulation. The methylation levels of the DLC1 isoforms in HCC samples were found significantly lower than those in the adjacent noncancerous tissues (all p < 0.0001). Also, we found that the expression of DLC1 could be bidirectionally regulated by the modified CRISPR-Cas9 system and the DNMTi. Moreover, the hypomethylation of DLC1 in HCC samples was connected with the presence of satellite lesions (p = 0.0305) and incomplete tumor capsule (p = 0.0204). Receiver operator characteristic curve analysis demonstrated that the methylation levels of DLC1 could be applied to discriminate HCC patients (area under the curve = 0.728, p < 0.0001). The hypomethylation status was a key regulatory mechanism of DLC1 expression and might serve as a potential biomarker for HCC.
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Copyright 2023, Mary Ann Liebert, Inc., publishers.
History
Published online: 13 March 2023
Published in print: March 2023
Accepted: 11 December 2022
Revision received: 11 November 2022
Received: 10 July 2022
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Authors' Contributions
J.P. and D.L. contributed equally to the conception of the study, the data analysis, and writing. X.F. and J.C. collected the samples and performed the bioinformatics analysis. S.J. and P.C. performed all biological experiments. H.L. and Y.L. contributed to the conceptualization and reviewed the article. All authors discussed the results and comments on the article.
Disclosure Statement
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.
Funding Information
This work was supported by National Natural Science Foundation of China (81872297, 81874059, and 82102105).
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