The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China.
Department of Cell Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
J Cell Biochem. 2020 Nov;121(11):4680-4689. doi: 10.1002/jcb.29693. Epub 2020 Mar 11.
The Iroquois homeobox gene 5 (IRX5), one of the members of the Iroquois homeobox family, has been identified to correlate with worse prognosis in many cancers, including colorectal cancer (CRC). In this study, upregulation of IRX5 revealed a great reduction in the proliferation of CRC colorectal cancer cell line SW480 and DLD-1, which was accompanied by G1/S arrest, increased expression in cyclin E1, P21, and P53 and a decrease in cyclin A2, B1, and D1. Furthermore, IRX5-mediated an increase expression of RH2A protein, the biomarker of DNA damage. Consequently, the SA-β-gal level is higher in IRX5-overexpression cells compared to control ones, which showed elevated DNA damage triggered cellular senescence. Recapitulating the above findings, IRX5 exhibited higher levels of genomic instability. IRX5 may be a perspective target for cancer therapy and it deserves further investigation.
同源异形盒基因 5（IRX5）是同源异形盒家族的成员之一，已被确定与许多癌症（包括结直肠癌）的预后不良相关。在这项研究中，IRX5 的上调显示出结直肠癌细胞系 SW480 和 DLD-1 的增殖大大减少，这伴随着 G1/S 期阻滞，细胞周期蛋白 E1、P21 和 P53 的表达增加，细胞周期蛋白 A2、B1 和 D1 的表达减少。此外，IRX5 介导 RH2A 蛋白的表达增加，该蛋白是 DNA 损伤的生物标志物。因此，与对照细胞相比，IRX5 过表达细胞中的 SA-β-gal 水平更高，这表明触发细胞衰老的 DNA 损伤增加。重现上述发现，IRX5 表现出更高水平的基因组不稳定性。IRX5 可能是癌症治疗的有前途的靶点，值得进一步研究。
