Hu Fangfang, Bai Zhibin, Wang Yang, Tang Haodong, Zhou Jiahua
Department of Hepatobiliary and Pancreatic Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China.
Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China.
Oncol Res. 2025 Jun 26;33(7):1723-1737. doi: 10.32604/or.2025.059631. eCollection 2025.
Kinesin-14 family protein 1 (KIFC1) is abnormally overexpressed in various cancers, and the transcription factor ETS variant 1 (ETV1) is an oncogenic transcription factor in tumors. The potential binding sites on the KIFC1 promoter by ETV1 were observed; however, no evidence supports that ETV1 targets KIFC1. Aims: This study aimed to investigate the relationship between KIFC1 and ETV1, and their effects and mechanisms in pancreatic cancer.
Pan-cancer analysis of KIFC1 expression was performed in GEPIA2 database. KIFC1 expression levels were determined by immunohistochemistry (IHC) in our pancreatic cancer cohort. The correlation between KIFC1 expression and prognosis, tumor mutation burden, tumor purity, mismatch repair, and high-frequency tumor mutated genes was analyzed using a series of bioinformatic tools. ETV1 targeting of KIFC1 promoter transcription was determined using luciferase reporter assay. KIFC1 knockdown and ETV1 overexpression were used to determine the role of the ETV1/KIFC1 axis in cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells and tumor growth .
KIFC1 expression was increased in clinical specimens and pancreatic cancer cell lines and positively correlated with tumor mutation burden, tumor purity, mismatch repair, and KRAS and TP53 mutations. High KIFC1 expression was significantly associated with poor prognosis. Knockdown of KIFC1 suppressed the proliferation, migration, and invasion of pancreatic cancer cells and tumor growth. ETV1 overexpression increased KIFC1 expression and affected KIFC1 transcription. ETV1 overexpression reversed the role of KIFC1 knockdown in inhibiting cell proliferation, invasion, migration, and EMT, as validated .
KIFC1 serves as a tumor activator in pancreatic cancer by promoting proliferation, migration, invasion, and tumor growth, which may be partly manipulated by ETV1.
驱动蛋白-14家族蛋白1（KIFC1）在多种癌症中异常过表达，转录因子ETS变异体1（ETV1）是肿瘤中的一种致癌转录因子。观察到ETV1在KIFC1启动子上的潜在结合位点；然而，没有证据支持ETV1靶向KIFC1。目的：本研究旨在探讨KIFC1与ETV1之间的关系及其在胰腺癌中的作用和机制。
在GEPIA2数据库中对KIFC1表达进行泛癌分析。通过免疫组织化学（IHC）在我们的胰腺癌队列中测定KIFC1表达水平。使用一系列生物信息学工具分析KIFC1表达与预后、肿瘤突变负荷、肿瘤纯度、错配修复和高频肿瘤突变基因之间的相关性。使用荧光素酶报告基因测定法确定ETV1对KIFC1启动子转录的靶向作用。使用KIFC1敲低和ETV1过表达来确定ETV1/KIFC1轴在胰腺癌细胞的增殖、迁移、侵袭和上皮-间质转化（EMT）以及肿瘤生长中的作用。
KIFC1在临床标本和胰腺癌细胞系中表达增加，与肿瘤突变负荷、肿瘤纯度、错配修复以及KRAS和TP53突变呈正相关。高KIFC1表达与不良预后显著相关。敲低KIFC1可抑制胰腺癌细胞的增殖、迁移和侵袭以及肿瘤生长。ETV1过表达增加KIFC1表达并影响KIFC1转录。如验证所示，ETV1过表达逆转了KIFC1敲低在抑制细胞增殖、侵袭、迁移和EMT中的作用。
KIFC1通过促进增殖、迁移、侵袭和肿瘤生长在胰腺癌中充当肿瘤激活剂，这可能部分受ETV1调控。
