Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Genes (Basel). 2023 Apr 27;14(5):995. doi: 10.3390/genes14050995.
Coronin proteins are actin-related proteins containing WD repeat domains encoded by seven genes (, , , , , , and ) in the human genome. Analysis of large cohort data from The Cancer Genome Atlas revealed that expression of , , , , and was significantly upregulated in pancreatic ductal adenocarcinoma (PDAC) tissues ( < 0.05). Moreover, high expression of and significantly predicted the 5 year survival rate of patients with PDAC ( = 0.0071 and = 0.0389, respectively). In this study, we focused on and investigated its functional significance and epigenetic regulation in PDAC cells. Knockdown assays using siRNAs targeting were performed in PDAC cells. Aggressive cancer cell phenotypes, especially cancer cell migration and invasion, were inhibited by knockdown. The involvement of microRNAs (miRNAs) is a molecular mechanism underlying the aberrant expression of cancer-related genes in cancer cells. Our analysis revealed that five miRNAs (, , , , and ) are putative candidate miRNAs regulating expression in PDAC cells. Importantly, all five miRNAs exhibited tumor-suppressive functions and four miRNAs except negatively regulated expression in PDAC cells. and its downstream signaling molecules are potential therapeutic targets in PDAC.
冠状蛋白是肌动蛋白相关蛋白,含有 WD 重复结构域,由人类基因组中的七个基因(、、、、、和)编码。对来自癌症基因组图谱的大型队列数据的分析显示,在胰腺导管腺癌(PDAC)组织中,、、、和的表达显著上调(<0.05)。此外,高表达和显著预测了 PDAC 患者的 5 年生存率(=0.0071 和=0.0389,分别)。在本研究中,我们专注于并研究了其在 PDAC 细胞中的功能意义和表观遗传调控。在 PDAC 细胞中用靶向的 siRNAs 进行了敲低实验。通过敲低抑制了侵袭性癌细胞表型,特别是癌细胞迁移和侵袭。miRNAs(miRNAs)的参与是癌细胞中癌症相关基因异常表达的分子机制。我们的分析表明,五种 miRNAs(、、、、和)是调节 PDAC 细胞中表达的潜在候选 miRNAs。重要的是,所有五种 miRNAs 都表现出肿瘤抑制功能,除了外的四种 miRNAs 负调控 PDAC 细胞中的表达。和其下游信号分子是 PDAC 的潜在治疗靶点。