Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Kayisdagi Cad. 26 Agustos Yerlesimi, 34755, Atasehir, Istanbul, Turkey.
National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, USA.
Mol Cell Biochem. 2018 Jan;437(1-2):133-142. doi: 10.1007/s11010-017-3101-2. Epub 2017 Jun 15.
Cell proliferation and migration are crucial in many physiological processes including development, cancer, tissue repair, and wound healing. Cell migration is regulated by several signaling molecules. Identification of genes related to cell migration is required to understand molecular mechanism of non-healing chronic wounds which is a major concern in clinics. In the current study, the role of cytoglobin (CYGB) gene in fıbroblast cell migration and proliferation was described. L929 mouse fibroblast cells were transduced with lentiviral particles for CYGB and GFP, and analyzed for cell proliferation and migration ability. Fibroblast cells overexpressing CYGB displayed decreased cell proliferation, colony formation capacity, and cell migration. Phosphorylation levels of mTOR and two downstream effectors S6 and 4E-BP1 which take part in PI3K/AKT/mTOR signaling declined in CYGB-overexpressing cells. Microarray analysis indicated that CYGB overexpression leads to downregulation of cell proliferation, migration, and tumor growth associated genes in L929 cell line. This study demonstrated the role of CYGB in fibroblast cell motility and proliferation. CYGB could be a promising candidate for further studies as a potential target for diseases related to cell migration such as cancer and chronic wound treatment.
细胞增殖和迁移在许多生理过程中至关重要，包括发育、癌症、组织修复和伤口愈合。细胞迁移受几种信号分子的调节。鉴定与细胞迁移相关的基因对于理解非愈合性慢性伤口的分子机制是非常重要的，这是临床上的一个主要关注点。在本研究中，描述了细胞色素氧化酶亚基 G（CYGB）基因在成纤维细胞迁移和增殖中的作用。用慢病毒颗粒转导 L929 小鼠成纤维细胞以过表达 CYGB 和 GFP，并分析细胞增殖和迁移能力。过表达 CYGB 的成纤维细胞表现出细胞增殖、集落形成能力和细胞迁移能力下降。参与 PI3K/AKT/mTOR 信号通路的 mTOR 和两个下游效应物 S6 和 4E-BP1 的磷酸化水平在过表达 CYGB 的细胞中下降。微阵列分析表明，CYGB 过表达导致 L929 细胞系中与细胞增殖、迁移和肿瘤生长相关的基因下调。本研究证明了 CYGB 在成纤维细胞运动和增殖中的作用。CYGB 可能是进一步研究的有前途的候选物，因为它可能成为与细胞迁移相关的疾病（如癌症和慢性伤口治疗）的潜在靶点。
