Xue Pengfei, Zheng Juan, Li Rongrong, Yan Lili, Wang Zhaohao, Jia Qingbin, Zhang Lianqun, Li Xin
Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng, China.
Joint Laboratory for Translational Medicine Research, Liaocheng People's Hospital, Liaocheng, China.
J Korean Neurosurg Soc. 2024 May;67(3):364-375. doi: 10.3340/jkns.2023.0155. Epub 2024 May 1.
Kinesin family member C1 (KIFC1), a non-essential kinesin-like motor protein, has been found to serve a crucial role in supernumerary centrosome clustering and the progression of several human cancer types. However, the role of KIFC1 in glioma has been rarely reported. Thus, the present study aimed to investigate the role of KIFC1 in glioma progression.
Online bioinformatics analysis was performed to determine the association between KIFC1 expression and clinical outcomes in glioma. Immunohistochemical staining was conducted to analyze the expression levels of KIFC1 in glioma and normal brain tissues. Furthermore, KIFC1 expression was knocked in the glioma cell lines, U251 and U87MG, and the functional roles of KIFC1 in cell proliferation, invasion and migration were analyzed using cell multiplication, wound healing and Transwell invasion assays, respectively. The autophagic flux and expression levels matrix metalloproteinase-2 (MMP2) were also determined using imaging flow cytometry, western blotting and a gelation zymography assay.
The results revealed that KIFC1 expression levels were significantly upregulated in glioma tissues compared with normal brain tissues, and the expression levels were positively associated with tumor grade. Patients with glioma with low KIFC1 expression levels had a more favorable prognosis compared with patients with high KIFC1 expression levels. In vitro, KIFC1 knockdown not only inhibited the proliferation, migration and invasion of glioma cells, but also increased the autophagic flux and downregulated the expression levels of MMP2.
Upregulation of KIFC1 expression may promote glioma progression and KIFC1 may serve as a potential prognostic biomarker and possible therapeutic target for glioma.
驱动蛋白家族成员C1（KIFC1）是一种非必需的类驱动蛋白运动蛋白，已发现在多余中心体聚集和多种人类癌症类型进展中起关键作用。然而，KIFC1在胶质瘤中的作用鲜有报道。因此，本研究旨在探讨KIFC1在胶质瘤进展中的作用。
进行在线生物信息学分析以确定KIFC1表达与胶质瘤临床结局之间的关联。进行免疫组织化学染色以分析KIFC1在胶质瘤和正常脑组织中的表达水平。此外，在胶质瘤细胞系U251和U87MG中敲入KIFC1表达，并分别使用细胞增殖、伤口愈合和Transwell侵袭试验分析KIFC1在细胞增殖、侵袭和迁移中的功能作用。还使用成像流式细胞术、蛋白质印迹和凝胶酶谱分析确定自噬通量和基质金属蛋白酶-2（MMP2）的表达水平。
结果显示，与正常脑组织相比，胶质瘤组织中KIFC1表达水平显著上调，且表达水平与肿瘤分级呈正相关。KIFC1表达水平低的胶质瘤患者预后优于KIFC1表达水平高的患者。在体外，KIFC1敲低不仅抑制了胶质瘤细胞的增殖、迁移和侵袭，还增加了自噬通量并下调了MMP2的表达水平。
KIFC1表达上调可能促进胶质瘤进展，KIFC1可能作为胶质瘤潜在的预后生物标志物和可能的治疗靶点。
