Cell Journal (Apr 2023)
Understanding The Regulatory Role of USP32 and SHMT2 in The Progression of Gastric Cancer
Abstract
Objective: Gastric cancer is the fifth most common neoplasm and the fourth reason for mortality globally. Incidencerates are highly variable and dependent on risk factors, epidemiologic and carcinogenesis patterns. Previous studiesreported that Helicobacter pylori (H. pylori) infection is one the strongest known risk factor for gastric cancer. USP32 isa deubiquitinating enzyme identified as a potential factor associated with tumor progression and a key player in cancerdevelopment. 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 completemechanism is not fully explored yet. The present study explored possible mechanism of action of USP32 and SHMT2in the progression of gastric cancer.Materials and Methods: In this experimental study, Capsaicin (0.3 g/kg/day) and H. pylori infection combination wasused to successfully initiate gastric cancer conditions in mice. It was followed by 40 and 70 days of treatment toestablish initial and advanced conditions of gastric cancer.Results: Histopathology confirmed formation of signet ring cell and initiation of cellular proliferation in the initial gastriccancer. More proliferative cells were also observed. In addition, tissue hardening was confirmed in the advancedstage 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 evidentwith less abnormal cell in initial gastric cancer. Reduction of SHMT2 level to one-fourth was observed in the advancedgastric cancer stages of USP32 silenced tissue.Conclusion: USP32 had a direct role in regulating SHMT2 expression, which attracted therapeutic target for futuretreatment.
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