整合素亚基阿尔法 2 (ITGA2) 在胰腺癌进展中的作用

R. K. Alfardan, W. N. Alismaeel
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引用次数: 0

摘要

背景:胰腺癌是一种相对少见的癌症,但它通常具有很强的侵袭性,并高度转移到身体的其他部位。研究潜在的基因标记物或基因靶向治疗可改善患者的早期预后和/或治疗。研究目的在本研究中,我们将 Integrin Subunit Alpha 2 (ITGA2) 鉴定为抑制胰腺癌进展的潜在靶点。材料与方法:本研究采用细胞周期分析、基因表达水平和细胞增殖测定作为研究方法。研究组间的比较采用双尾学生 t 检验。结果对转化细胞系的细胞周期分析表明,在敲除 ITGA2 表达后,细胞的 G0/G1 期增加,并进入细胞周期停滞期(静止期)。另一方面,敲除 ITGA2 会抑制转移标志物波形蛋白的表达,从而影响细胞系的间质向上皮转化和迁移的可能性。此外,ITGA2 还能通过下调细胞外基质蛋白(ECM 蛋白)LAMB3 和 LAMC2 来操纵肿瘤微环境。结论ITGA2 下调可减少细胞增殖,诱导细胞周期停滞,降低胰腺癌转移的可能性。
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The Role of Integrin Subunit Alpha 2 (ITGA2) in Pancreatic Cancer Progression
Background: Pancreatic cancer is a relatively uncommon type of cancer, although it is often very aggressive and highly metastases to other parts of the body. Investigating a potential gene marker or gene targeted therapy can improve the patient’s early prognosis and/or treatment. Objectives: In this study, we identify Integrin Subunit Alpha 2 (ITGA2) as a potential target in inhibiting pancreatic cancer progression. Materials and Methods: Cell cycle analysis, gene expression level, and cell proliferation assay are implanted in this study as investigational methods. Two-tailed student's t test is used to compare between the studied groups. Results: Cell cycle analysis for the transformed cell lines revealed increasing in G0/G1 phase and entering the cells the cell cycle arrest (quiescence) after knocking down ITGA2 expression. On the other hand, knocking down the ITGA2 effect, the mesenchymal to epithelial transition and the migration possibility of the cell lines by inhibiting the expression of metastatic marker vimentin. Furthermore, ITGA2 can manipulate the tumor microenvironment by downregulating extracellular matrix proteins (ECM-proteins) LAMB3, and LAMC2. Conclusion: ITGA2 downregulation reduces the cell proliferation, induces the cell cycle arrest, and reduce the possibility of metastasis in pancreatic cancer.
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