Inositol 1,4,5‑trisphosphate receptor type 3 is involved in resistance to apoptosis and maintenance of human hepatocellular carcinoma
| Autor: | Antônio Carlos Melo Lima Filho, Marcone Loiola dos Santos, Carlos Alberto Xavier Gonçalves, Rodrigo M. Florentino, Paula Vieira Teixeira Vidigal, Vitor Lima Coelho, Andressa França, M. Fatima Leite, Cristiano Xavier Lima, Paulo Henrique Costa Diniz, Giselle Foureaux, Michael H. Nathanson, Fernanda O. Lemos |
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| Rok vydání: | 2021 |
| Předmět: |
mitosis
Cancer Research Oncogene Cell apoptosis Cancer Articles Biology Cell cycle calcium signaling medicine.disease Molecular medicine digestive system diseases chronic diseases liver cancer chemistry.chemical_compound medicine.anatomical_structure Oncology chemistry Apoptosis Hepatocellular carcinoma medicine Cancer research Inositol |
| Zdroj: | Oncology Letters |
| ISSN: | 1792-1082 1792-1074 |
| Popis: | The expression of the inositol 1,4,5-trisphosphate receptor type 3 (ITRP3) in hepatocytes is a common event in the pathogenesis of hepatocellular carcinoma (HCC), regardless of the type of underlying liver disease. However, it is not known whether ITPR3 expression in hepatocytes is involved in tumor maintenance. The aim of the present study was to determine whether there is an association between ITPR3 expression and clinical and morphological parameters using HCC samples obtained from liver explants from patients (n=53) with different etiologies of underlying chronic liver disease (CLD). ITPR3 expression, mitosis and apoptosis were analyzed in human liver samples by immunohistochemistry. Clinical and event-free survival data were combined to assess the relationship between ITPR3 and liver cancer growth in patients. RNA sequencing analysis was performed to identify apoptotic genes altered by ITPR3 expression in a liver tumor cell line. ITPR3 was highly expressed in HCC tumor cells relative to adjacent CLD tissue and healthy livers. There was an inverse correlation between ITPR3 expression and mitotic and apoptotic indices in HCC, suggesting that ITPR3 contributed to the maintenance of HCC by promoting resistance to apoptosis. This was confirmed by the upregulation of CTSB, CHOP and GADD45, genes involved in the apoptotic pathway in HCC. The expression of ITPR3 in the liver may be a promising prognostic marker of HCC. |
| Databáze: | OpenAIRE |
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