Fujian Provincial Key Laboratory of Transplant Biology, Department of Urology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou 350025, Fujian, P.R. China.
Office of Science Education, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou 350025, Fujian, P.R. China.
Aging (Albany NY). 2020 Apr 9;12(7):5992-6017. doi: 10.18632/aging.102991.
KIAA0101, previously identified as PCNA-associated factor, is overexpressed among almost majority of human cancers and has emerged as an important regulator of cancer progression; however, its function in human nasopharyngeal carcinoma (NPC) remain unknown. Integrated bioinformatics approaches were employed to determine the KIAA0101 expressions in the NPC samples. Lentiviral vectors carrying KIAA0101 shRNA were constructed and stable transfected cells were validated by qRT-PCR and western blot. Cellular functions were then evaluated by MTT, colony formation, Brdu staining, and flow cytometry. Mechanistic studies were systematically investigated by UCSC Genome Browser, GEO, UALCAN, QIAGEN, PROMO and JASPAR, ChIP, and the cBioPortal, et al. The results showed that KIAA0101 ranked top overexpressed gene lists in GSE6631 dataset. KIAA0101 was highly expressed in NPC tissues and cell lines. Furthermore, knockdown of KIAA0101 significantly inhibited cell proliferation and DNA replication, promoted apoptosis and cell cycle arrest in vitro. Meanwhile, the mechanistic study revealed that MAP kinase phosphorylation-dependent activation of ELK1 may enhance neighbor gene expressions of KIAA0101 and TRIP4 by binding both promotor regions in the NPC cells. Taken together, our findings indicate that overexpression of KIAA0101 activated by MAP kinase phosphorylation-dependent activation of ELK1 may play an important role in NPC progression.
KIAA0101,以前被鉴定为 PCNA 相关因子,在几乎大多数人类癌症中过表达,已成为癌症进展的重要调节因子;然而,其在人鼻咽癌(NPC)中的功能尚不清楚。采用整合生物信息学方法来确定 NPC 样本中的 KIAA0101 表达。构建了携带 KIAA0101 shRNA 的慢病毒载体,并通过 qRT-PCR 和 Western blot 验证了稳定转染的细胞。然后通过 MTT、集落形成、Brdu 染色和流式细胞术评估细胞功能。通过 UCSC Genome Browser、GEO、UALCAN、QIAGEN、PROMO 和 JASPAR、ChIP 和 cBioPortal 等系统地研究了机制研究。结果表明,KIAA0101 在 GSE6631 数据集的高表达基因列表中排名第一。KIAA0101 在 NPC 组织和细胞系中高表达。此外,下调 KIAA0101 显著抑制细胞增殖和 DNA 复制,促进体外细胞凋亡和细胞周期停滞。同时,机制研究表明,MAP 激酶磷酸化依赖性 ELK1 的激活可能通过结合 NPC 细胞中两个启动子区域来增强 KIAA0101 和 TRIP4 的邻近基因表达。总之,我们的研究结果表明,MAP 激酶磷酸化依赖性 ELK1 的激活导致的 KIAA0101 的过表达可能在 NPC 进展中发挥重要作用。