Inositol 1,4,5‑trisphosphate receptor type 3 is involved in resistance to apoptosis and maintenance of human hepatocellular carcinoma

Dos Santos,Marcone Loiola; França,Andressa; Lima Filho,Antônio Carlos Melo; Florentino,Rodrigo M.; Diniz,Paulo Henrique; Lemos,Fernanda Oliveira; Gonçalves,Carlos Alberto Xavier; Coelho,Vitor Lima; Lima,Cristiano Xavier; Foureaux,Giselle; Nathanson,Michael H.; Vidigal,Paula Vieira Teixeira; Leite,M. Fátima

doi:10.3892/ol.2021.13150

January-2022 Volume 23 Issue 1

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January-2022 Volume 23 Issue 1

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Article Open Access

Inositol 1,4,5‑trisphosphate receptor type 3 is involved in resistance to apoptosis and maintenance of human hepatocellular carcinoma

Authors:
- Marcone Loiola Dos Santos
- Andressa França
- Antônio Carlos Melo Lima Filho
- Rodrigo M. Florentino
- Paulo Henrique Diniz
- Fernanda Oliveira Lemos
- Carlos Alberto Xavier Gonçalves
- Vitor Lima Coelho
- Cristiano Xavier Lima
- Giselle Foureaux
- Michael H. Nathanson
- Paula Vieira Teixeira Vidigal
- M. Fátima Leite
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Affiliations: Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais 31270‑901, Brazil, Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais 31270‑901, Brazil, Department of Internal Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais 31270‑901, Brazil, Coordination of Biotechnology, SENAI's Innovation Institute for Biosynthetics and Fibers, SENAI CETIQT, Rio de Janeiro 20961‑020, Brazil, Department of Surgery, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais 30 130‑100, Brazil, Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520‑8056, USA, Department of Pathological Anatomy and Forensic Medicine of Hospital das Clínicas, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais 30 130‑100, Brazil

Copyright: © Dos Santos et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 32
|
Published online on: November 25, 2021

https://doi.org/10.3892/ol.2021.13150
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Abstract

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.

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