Kim Wootae, Pyo Jaehyuk, Noh Byeong-Joo, Jeong Joo-Won, Lee Juhie, Kim Ja-Eun
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
Department of Pathology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Oncotarget. 2017 Dec 13;9(1):1143-1155. doi: 10.18632/oncotarget.23199. eCollection 2018 Jan 2.
Cell cycle and apoptosis regulator 2 (CCAR2) is a multifaceted protein that controls diverse cellular functions; however, its function in cancer is unclear. To better understand its potential role in cancer, we examined gene expression patterns regulated by CCAR2 in cervical cancer cells. Cytokine and chemokine production by CCAR2-deficient cells increased under oxidative conditions. In particular, HO-treated CCAR2-depleted cells showed a significant increase in interleukin-8 (IL-8) production, indicating a negative regulation of IL-8 by CCAR2. Upregulation of IL-8 expression in CCAR2-deficient cells occurred via activation of transcription factor AP-1. The negative correlation between CCAR2 and IL-8 expression was confirmed by examining mRNA and protein levels in tissues from cervical cancer patients. Furthermore, CCAR2-regulated IL-8 expression is associated with a shorter survival of cervical cancer patients. Overall, the data suggest that CCAR2 plays a critical role in controlling both the cancer secretome and cancer progression.
细胞周期与凋亡调节因子2（CCAR2）是一种具有多种功能的蛋白质，可控制多种细胞功能；然而，其在癌症中的作用尚不清楚。为了更好地了解其在癌症中的潜在作用，我们研究了CCAR2在宫颈癌细胞中调控的基因表达模式。在氧化条件下，CCAR2缺陷细胞产生的细胞因子和趋化因子增加。特别是，经过氧化氢（HO）处理的CCAR2缺失细胞中白细胞介素-8（IL-8）的产生显著增加，表明CCAR2对IL-8具有负调控作用。CCAR2缺陷细胞中IL-8表达的上调是通过转录因子AP-1的激活实现的。通过检测宫颈癌患者组织中的mRNA和蛋白质水平，证实了CCAR2与IL-8表达之间呈负相关。此外，CCAR2调控的IL-8表达与宫颈癌患者较短的生存期相关。总体而言，数据表明CCAR2在控制癌症分泌组和癌症进展中起着关键作用。
