The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, Guangdong, People's Republic of China.
Aging (Albany NY). 2021 May 17;13(10):14088-14108. doi: 10.18632/aging.203028.
Caspase1 (CASP1) is a gene that encodes multiple proteins related to cell death. Nevertheless, the function of CASP1 in the pathogenesis of AML is still unclear. In the present study, a detailed analysis of cancer versus normal samples was performed to explore the relationship between CASP1 and leukemia. We used sequencing data from multiple cancer gene databases to analyze the gene expression and regulatory network of CASP1 in leukemia. We discovered that mRNA expression levels of CASP1 are increased in leukemia cell lines, especially in acute myelocytic leukemia (AML). Then, we verified the mRNA expression of CASP1 in AML clinical samples and observed significantly higher expression of CASP1 in relapsed AML patients. High CASP1 expression was associated with poor prognosis and CASP1 inhibition could impair the proliferation of AML cells. Related functional network identification suggests that CASP1 regulates apoptosis, immune and inflammatory response via pathways involving LYN, LCK, and the E2F family. These findings suggest that CASP1 probably contributes to the pathogenesis, and identify CASP1 as a factor for predicting the prognosis and as a therapeutic target of AML patients.
Caspase1（CASP1）是一种编码与细胞死亡相关的多种蛋白质的基因。然而，CASP1 在 AML 的发病机制中的作用仍不清楚。在本研究中，对癌症与正常样本进行了详细分析，以探讨 CASP1 与白血病之间的关系。我们使用来自多个癌症基因数据库的测序数据来分析 CASP1 在白血病中的基因表达和调控网络。我们发现，CASP1 的 mRNA 表达水平在白血病细胞系中升高，尤其是在急性髓细胞白血病（AML）中。然后，我们验证了 AML 临床样本中 CASP1 的 mRNA 表达，发现复发 AML 患者中 CASP1 的表达明显升高。高 CASP1 表达与预后不良相关，抑制 CASP1 可损害 AML 细胞的增殖。相关功能网络鉴定表明，CASP1 通过涉及 LYN、LCK 和 E2F 家族的途径调节细胞凋亡、免疫和炎症反应。这些发现表明 CASP1 可能有助于发病机制，并将 CASP1 鉴定为预测 AML 患者预后的因素和治疗靶点。
