Geng Rongxin, Zhu Xiaonan, Tao Xiang, Liu Junhui, Xu Haitao
Department of Neurosurgery, Renmin Hospital of Wuhan University, No. 238, Jiefang Road, Wuhan City, Hubei Province, China.
Department of Neurosurgery, Renmin Hospital of Wuhan University, No. 238, Jiefang Road, Wuhan City, Hubei Province, China.
Transl Oncol. 2022 Jan;15(1):101299. doi: 10.1016/j.tranon.2021.101299. Epub 2021 Dec 1.
EIF1A encodes a translation initiation factor in eukaryocyte and aberrant expression of EIF1A is deemed to be associated with dysfunctions in intracranial diseases. The goal of this research was to explore the impacts of EIF1A on progression of human pituitary adenoma (PA). We employed immunohistochemistry to assess the expression of EIF1A in PA and para-carcinoma tissues. After constructing EIF1A-knockdown cell models via lentivirus infection, we examined cell proliferation through CCK-8 assay and Celigo cell counting assay. Flow cytometry was utilized to detect cell apoptosis and the migration ability of experimental cells was estimated using wound-healing assay and Transwell assay. The activity of the apoptosis-related factor, Caspase 3, was also examined via Caspase 3 activity assay. Lastly, in vivo xenograft mouse models were established to verify findings derived from in vitro cell models. Our results affirmed upregulation of EIF1A in PA cells and revealed that depletion of EIF1A could seriously limit cell proliferation and weaken the capacity of cell migration, and also enhance apoptosis of tumor cells. Mechanistically, degradation in cell growth mediated by EIF1A knockdown may involve in activation of MAPK signaling but inactivation of PI3K/AKT signaling pathway. This study indicates EIF1A plays a prominent role in facilitating tumor cell proliferation and migration which may further contribute to PA progression.
EIF1A在真核细胞中编码一种翻译起始因子，EIF1A的异常表达被认为与颅内疾病的功能障碍有关。本研究的目的是探讨EIF1A对人垂体腺瘤（PA）进展的影响。我们采用免疫组织化学方法评估EIF1A在PA和癌旁组织中的表达。通过慢病毒感染构建EIF1A敲低细胞模型后，我们通过CCK-8法和Celigo细胞计数法检测细胞增殖。利用流式细胞术检测细胞凋亡，并使用伤口愈合试验和Transwell试验评估实验细胞的迁移能力。还通过Caspase 3活性测定法检测凋亡相关因子Caspase 3的活性。最后，建立体内异种移植小鼠模型以验证体外细胞模型的结果。我们的结果证实了PA细胞中EIF1A的上调，并表明EIF1A的缺失可严重限制细胞增殖并削弱细胞迁移能力，还可增强肿瘤细胞的凋亡。机制上，EIF1A敲低介导的细胞生长降解可能涉及MAPK信号的激活，但PI3K/AKT信号通路的失活。本研究表明EIF1A在促进肿瘤细胞增殖和迁移中起重要作用，这可能进一步促进PA的进展。
