Tan Jingyi, Xu Wenfeng, Lei Lei, Liu Hui, Wang Hong, Cao Xian, Xu Man
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, People's Republic of China.
Institute of Life Science, Chongqing Medical University, Chongqing 400016, People's Republic of China.
Onco Targets Ther. 2020 May 8;13:3953-3963. doi: 10.2147/OTT.S228656. eCollection 2020.
Aurora kinase A (AURKA), which belongs to the serine/threonine protein kinase family, has been identified as a key driver of the genesis and progression of diverse tumors. The aim of this study was to determine the clinical significance of AURKA in patients with hepatoblastoma (HB) and the effect of inhibiting AURKA in the HB cell line HuH-6.
The expression of AURKA in HB tissue and adjacent normal liver tissue was detected by immunohistochemistry. Then, statistical analysis was performed to evaluate the association between AURKA expression and the clinicopathological characteristics of HB. The effect of AURKA knockdown on cell viability was assessed by CCK-8 assay. EdU and CCK-8 assays, Western blotting, flow cytometry, and transmission electron microscopy (TEM) were used to examine the effect of alisertib (ALS), a selective AURKA small-molecule inhibitor, on the cell cycle, proliferation, apoptosis, and autophagy in HuH-6 human hepatoblastoma cells.
The expression of AURKA was significantly higher in HB tissue than in adjacent normal tissue. Furthermore, high AURKA expression was associated with advanced Children's Oncology Group (COG) stage and tumor metastasis of HB. In vitro, AURKA knockdown significantly reduced the viability of HuH-6 cells, while ALS treatment significantly suppressed HuH-6 cell proliferation and induced G1-phase cell cycle arrest by reducing cyclin-D1 expression. Moreover, ALS promoted apoptosis and autophagy by decreasing the activity of p38 MAPK in HuH-6 cells.
High expression of AURKA is a potential predictor of poor prognosis in HB patients. AURKA knockdown reduced the viability of HuH-6 cells, and ALS treatment inhibited cell proliferation and induced apoptosis and autophagy via the p38 MAPK signaling pathway. Our results suggest that AURKA may be a novel therapeutic target and ALS a potential therapeutic drug for the treatment of HB.
极光激酶A（AURKA）属于丝氨酸/苏氨酸蛋白激酶家族，已被确定为多种肿瘤发生和进展的关键驱动因素。本研究旨在确定AURKA在肝母细胞瘤（HB）患者中的临床意义以及抑制AURKA对HB细胞系HuH-6的影响。
采用免疫组织化学法检测HB组织及相邻正常肝组织中AURKA的表达。然后进行统计分析，以评估AURKA表达与HB临床病理特征之间的关联。通过CCK-8法评估AURKA敲低对细胞活力的影响。采用EdU和CCK-8法、蛋白质免疫印迹法、流式细胞术以及透射电子显微镜（TEM）检测选择性AURKA小分子抑制剂阿利西替尼（ALS）对HuH-6人肝母细胞瘤细胞的细胞周期、增殖、凋亡和自噬的影响。
AURKA在HB组织中的表达明显高于相邻正常组织。此外，AURKA高表达与儿童肿瘤学组（COG）晚期阶段及HB的肿瘤转移相关。在体外，AURKA敲低显著降低了HuH-6细胞的活力，而ALS处理显著抑制了HuH-6细胞的增殖，并通过降低细胞周期蛋白D1的表达诱导G1期细胞周期阻滞。此外，ALS通过降低HuH-6细胞中p38丝裂原活化蛋白激酶的活性促进凋亡和自噬。
AURKA高表达是HB患者预后不良的潜在预测指标。AURKA敲低降低了HuH-6细胞的活力，ALS处理通过p38丝裂原活化蛋白激酶信号通路抑制细胞增殖并诱导凋亡和自噬。我们的结果表明，AURKA可能是治疗HB的新型治疗靶点，而ALS可能是潜在的治疗药物。
