Understanding The Regulatory Role of USP32 and SHMT2 in The Progression of Gastric Cancer

Document Type : Original Article


1 Department of Gastrointestinal Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China

2 Department of Emergency, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China

3 Department of Gastrointestinal Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China, 750001


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


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