了解USP32和SHMT2在胃癌进展中的调控作用。
Understanding The Regulatory Role of USP32 and SHMT2 in The Progression of Gastric Cancer.
作者信息
Li Jun, Bo Yafei, Ding Bo, Wang Lei
机构信息
Department of Gastrointestinal Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.
Department of Emergency, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.
出版信息
Cell J. 2023 Apr 1;25(4):222-228. doi: 10.22074/cellj.2022.557384.1046.
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 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 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.
目的
胃癌是全球第五大常见肿瘤，也是第四大致死原因。发病率差异很大，取决于风险因素、流行病学和致癌模式。既往研究报道，感染是已知最强的胃癌风险因素之一。USP32是一种去泛素化酶，被确定为与肿瘤进展相关的潜在因素以及癌症发展的关键因素。另一方面，SHMT2参与丝氨酸 - 甘氨酸代谢以支持癌细胞增殖。据报道，USP32和SHMT2在包括胃癌在内的许多癌症类型中均上调，但其完整机制尚未完全阐明。本研究探讨了USP32和SHMT2在胃癌进展中的可能作用机制。
材料与方法
在本实验研究中，使用辣椒素（0.3 g/kg/天）与感染联合，成功诱导小鼠发生胃癌。随后进行40天和70天的治疗，以建立胃癌的初始和进展期状态。
结果
组织病理学证实初始胃癌中出现印戒细胞并启动细胞增殖。还观察到更多增殖细胞。此外，在胃癌进展期证实有组织硬化。随着胃癌进展，USP32和SHMT2表达呈进行性上调。免疫组织化学显示，其在异常细胞中有信号，在癌症进展期有高强度信号。在USP32沉默组织中，SHMT2表达完全被阻断，胃癌发展逆转，初始胃癌中异常细胞减少。在USP32沉默组织的晚期胃癌阶段，观察到SHMT2水平降低至四分之一。
结论
USP32在调节SHMT2表达中起直接作用，这为未来治疗提供了治疗靶点。
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