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Understanding The Regulatory Role of USP32 and SHMT2 in The Progression of Gastric Cancer
OBJECTIVE: Gastric cancer is the fifth most common neoplasm and the fourth reason for mortality globally. Incidence rates are highly variable and dependent on risk factors, epidemiologic and carcinogenesis patterns. Previous studies reported that Helicobacter pylori (H. pylori) infection is one the...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Royan Institute
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10201363/ https://www.ncbi.nlm.nih.gov/pubmed/37210642 http://dx.doi.org/10.22074/CELLJ.2022.557384.1046 |
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author | Li, Jun Bo, Yafei Ding, Bo Wang, Lei |
author_facet | Li, Jun Bo, Yafei Ding, Bo Wang, Lei |
author_sort | Li, Jun |
collection | PubMed |
description | OBJECTIVE: Gastric cancer is the fifth most common neoplasm and the fourth reason for mortality globally. Incidence rates are highly variable and dependent on risk factors, epidemiologic and carcinogenesis patterns. Previous studies reported that Helicobacter pylori (H. pylori) infection is one the strongest known risk factor for gastric cancer. USP32 is a deubiquitinating enzyme identified as a potential factor associated with tumor progression and a key player in cancer development. On the other hand, SHMT2 is involved in serine-glycine metabolism to support cancer cell proliferation. Both USP32 and SHMT2 are reported to be upregulated in many cancer types, including gastric cancer, but its complete mechanism is not fully explored yet. The present study explored possible mechanism of action of USP32 and SHMT2 in the progression of gastric cancer. MATERIALS AND METHODS: In this experimental study, Capsaicin (0.3 g/kg/day) and H. pylori infection combination was used to successfully initiate gastric cancer conditions in mice. It was followed by 40 and 70 days of treatment to establish initial and advanced conditions of gastric cancer. RESULTS: Histopathology confirmed formation of signet ring cell and initiation of cellular proliferation in the initial gastric cancer. More proliferative cells were also observed. In addition, tissue hardening was confirmed in the advanced stage of gastric cancer. USP32 and SHMT2 showed progressive upregulated expression, as gastric cancer progress. Immunohistologically, it showed signals in abnormal cells and high-intensity signals in the advanced stage of cancer. In USP32 silenced tissue, expression of SHMT2 was completely blocked and reverted cancer development as evident with less abnormal cell in initial gastric cancer. Reduction of SHMT2 level to one-fourth was observed in the advanced gastric cancer stages of USP32 silenced tissue. CONCLUSION: USP32 had a direct role in regulating SHMT2 expression, which attracted therapeutic target for future treatment. |
format | Online Article Text |
id | pubmed-10201363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Royan Institute |
record_format | MEDLINE/PubMed |
spelling | pubmed-102013632023-05-23 Understanding The Regulatory Role of USP32 and SHMT2 in The Progression of Gastric Cancer Li, Jun Bo, Yafei Ding, Bo Wang, Lei Cell J Original Article OBJECTIVE: Gastric cancer is the fifth most common neoplasm and the fourth reason for mortality globally. Incidence rates are highly variable and dependent on risk factors, epidemiologic and carcinogenesis patterns. Previous studies reported that Helicobacter pylori (H. pylori) infection is one the strongest known risk factor for gastric cancer. USP32 is a deubiquitinating enzyme identified as a potential factor associated with tumor progression and a key player in cancer development. On the other hand, SHMT2 is involved in serine-glycine metabolism to support cancer cell proliferation. Both USP32 and SHMT2 are reported to be upregulated in many cancer types, including gastric cancer, but its complete mechanism is not fully explored yet. The present study explored possible mechanism of action of USP32 and SHMT2 in the progression of gastric cancer. MATERIALS AND METHODS: In this experimental study, Capsaicin (0.3 g/kg/day) and H. pylori infection combination was used to successfully initiate gastric cancer conditions in mice. It was followed by 40 and 70 days of treatment to establish initial and advanced conditions of gastric cancer. RESULTS: Histopathology confirmed formation of signet ring cell and initiation of cellular proliferation in the initial gastric cancer. More proliferative cells were also observed. In addition, tissue hardening was confirmed in the advanced stage of gastric cancer. USP32 and SHMT2 showed progressive upregulated expression, as gastric cancer progress. Immunohistologically, it showed signals in abnormal cells and high-intensity signals in the advanced stage of cancer. In USP32 silenced tissue, expression of SHMT2 was completely blocked and reverted cancer development as evident with less abnormal cell in initial gastric cancer. Reduction of SHMT2 level to one-fourth was observed in the advanced gastric cancer stages of USP32 silenced tissue. CONCLUSION: USP32 had a direct role in regulating SHMT2 expression, which attracted therapeutic target for future treatment. Royan Institute 2023-04 2023-04-01 /pmc/articles/PMC10201363/ /pubmed/37210642 http://dx.doi.org/10.22074/CELLJ.2022.557384.1046 Text en Any use, distribution, reproduction or abstract of this publication in any medium, with the exception of commercial purposes, is permitted provided the original work is properly cited. https://creativecommons.org/licenses/by-nc/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial 3.0 (CC BY-NC 3.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Li, Jun Bo, Yafei Ding, Bo Wang, Lei Understanding The Regulatory Role of USP32 and SHMT2 in The Progression of Gastric Cancer |
title | Understanding The Regulatory Role of USP32 and SHMT2 in The
Progression of Gastric Cancer |
title_full | Understanding The Regulatory Role of USP32 and SHMT2 in The
Progression of Gastric Cancer |
title_fullStr | Understanding The Regulatory Role of USP32 and SHMT2 in The
Progression of Gastric Cancer |
title_full_unstemmed | Understanding The Regulatory Role of USP32 and SHMT2 in The
Progression of Gastric Cancer |
title_short | Understanding The Regulatory Role of USP32 and SHMT2 in The
Progression of Gastric Cancer |
title_sort | understanding the regulatory role of usp32 and shmt2 in the
progression of gastric cancer |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10201363/ https://www.ncbi.nlm.nih.gov/pubmed/37210642 http://dx.doi.org/10.22074/CELLJ.2022.557384.1046 |
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