Liu Junhui, Gao Lun, Liao Jianmin, Yang Ji'an, Yuan Fan'en, Chen Qianxue
Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.
Ann Transl Med. 2021 Feb;9(3):260. doi: 10.21037/atm-20-3219.
Kiaa0101, a regulator of cell proliferation, is overexpressed in many malignant tumors. However, its role in promoting invasion of glioma is poorly understood. Here, we investigated the effects of Kiaa0101 on glioma invasion and elucidated the underlying mechanisms of action.
We analyzed Kiaa0101 expression using datasets from four public databases, namely TCGA, CGGA, Gravendeel and Rembrandt as well as experimentally on 123 glioma samples via western blot (WB), RT-PCR and immunohistochemistry (IHC). We further quantified migration and invasion using wound healing and transwell assays. WB, IHC and immunofluorescence (IF) were used to detect expression of invasion related markers. Moreover, we detected tumor invasion of glioma cells in 5-week-old Balb/c nude mice.
Kiaa0101 was upregulated in glioma, relative to non-tumor brain tissues, with the expression increasing with increase in glioma grade. Kiaa0101 mRNA expression was especially enriched in isocitrate dehydrogenase (IDH)1 wild-type glioma. Kaplan-Meier analysis, based on the aforementioned datasets, revealed that high Kiaa0101 levels were significantly associated with worse overall survival. Besides, shRNA-mediated Kiaa0101 knockdown inhibited migration and invasion of glioma cells by reducing snail1 expression both and , whereas its upregulation enhanced malignant behaviors of these cells. Furthermore, Kiaa0101 regulated snail1 expression by activating the p38MAPK signaling pathway.
Our findings strongly indicate that Kiaa0101 is a prognostic biomarker for malignant tumors, and its inhibition may be an effective strategy for treating glioma.
Kiaa0101作为一种细胞增殖调节因子，在许多恶性肿瘤中均有过表达。然而，其在促进胶质瘤侵袭方面的作用尚不清楚。在此，我们研究了Kiaa0101对胶质瘤侵袭的影响，并阐明了其潜在的作用机制。
我们使用来自四个公共数据库（即TCGA、CGGA、Gravendeel和Rembrandt）的数据集分析了Kiaa0101的表达情况，并通过蛋白质免疫印迹法（WB）、逆转录聚合酶链反应（RT-PCR）和免疫组织化学（IHC）对123例胶质瘤样本进行了实验分析。我们进一步使用伤口愈合实验和Transwell实验对迁移和侵袭进行了定量分析。通过WB、IHC和免疫荧光（IF）检测侵袭相关标志物的表达。此外，我们检测了5周龄Balb/c裸鼠体内胶质瘤细胞的肿瘤侵袭情况。
相对于非肿瘤脑组织，Kiaa0101在胶质瘤中上调，其表达随胶质瘤分级的增加而增加。Kiaa0101 mRNA表达在异柠檬酸脱氢酶（IDH）1野生型胶质瘤中尤其丰富。基于上述数据集的Kaplan-Meier分析显示，Kiaa0101水平高与总生存期较差显著相关。此外，短发夹RNA（shRNA）介导的Kiaa0101敲低通过降低snail1的表达抑制了胶质瘤细胞的迁移和侵袭，而其上调则增强了这些细胞的恶性行为。此外，Kiaa0101通过激活p38丝裂原活化蛋白激酶（p38MAPK）信号通路调节snail1的表达。
我们的研究结果有力地表明，Kiaa0101是恶性肿瘤的预后生物标志物，抑制它可能是治疗胶质瘤的有效策略。
