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Article

The Relevance of SOCS1 Methylation and Epigenetic Therapy in Diverse Cell Populations of Hepatocellular Carcinoma

1
Fondazione Italiana Fegato ONLUS, AREA Science Park, Campus Basovizza, 34149 Trieste, Italy
2
Doctoral School in Molecular Biomedicine, University of Trieste, 34127 Trieste, Italy
3
Hepatology Society of the Philippines, Quezon City 1105, Philippines
4
Liver Unit, Clinical Department of Medical, Surgical and Health Sciences, Trieste University, 34127 Trieste, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Chia Yen Dai
Received: 26 August 2021 / Revised: 27 September 2021 / Accepted: 29 September 2021 / Published: 2 October 2021
(This article belongs to the Special Issue Biomarkers in Hepatocellular Carcinoma)
The suppressor of cytokine signaling 1 (SOCS1) is a tumor suppressor gene found to be hypermethylated in cancers. It is involved in the oncogenic transformation of cirrhotic liver tissues. Here, we investigated the clinical relevance of SOCS1 methylation and modulation upon epigenetic therapy in diverse cellular populations of hepatocellular carcinoma (HCC). HCC clinical specimens were evaluated for SOCS1 methylation and mRNA expression. The effect of 5-Azacytidine (5-AZA), a demethylation agent, was assessed in different subtypes of HCC cells. We demonstrated that the presence of SOCS1 methylation was significantly higher in HCC compared to peri-HCC and non-tumoral tissues (52% vs. 13% vs. 14%, respectively, p < 0.001). In vitro treatment with a non-toxic concentration of 5-AZA significantly reduced DNMT1 protein expression for stromal subtype lines (83%, 73%, and 79%, for HLE, HLF, and JHH6, respectively, p < 0.01) compared to cancer stem cell (CSC) lines (17% and 10%, for HepG2 and Huh7, respectively), with the strongest reduction in non-tumoral IHH cells (93%, p < 0.001). 5-AZA modulated the SOCS1 expression in different extents among the cells. It was restored in CSC HCC HepG2 and Huh7 more efficiently than sorafenib. This study indicated the relevance of SOCS1 methylation in HCC and how cellular heterogeneity influences the response to epigenetic therapy. View Full-Text
Keywords: hepatocellular carcinoma; SOCS1; epigenetic therapy; DNA methylation; tumor heterogeneity hepatocellular carcinoma; SOCS1; epigenetic therapy; DNA methylation; tumor heterogeneity
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MDPI and ACS Style

Cabral, L.K.D.; Reyes, P.A.C.; Crocè, L.S.; Tiribelli, C.; Sukowati, C.H.C. The Relevance of SOCS1 Methylation and Epigenetic Therapy in Diverse Cell Populations of Hepatocellular Carcinoma. Diagnostics 2021, 11, 1825. https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11101825

AMA Style

Cabral LKD, Reyes PAC, Crocè LS, Tiribelli C, Sukowati CHC. The Relevance of SOCS1 Methylation and Epigenetic Therapy in Diverse Cell Populations of Hepatocellular Carcinoma. Diagnostics. 2021; 11(10):1825. https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11101825

Chicago/Turabian Style

Cabral, Loraine K.D., Peter A.C. Reyes, Lory S. Crocè, Claudio Tiribelli, and Caecilia H.C. Sukowati 2021. "The Relevance of SOCS1 Methylation and Epigenetic Therapy in Diverse Cell Populations of Hepatocellular Carcinoma" Diagnostics 11, no. 10: 1825. https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11101825

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