Department of Pathology, Harbin Medical University, Harbin 150081, China.
Department of Oncology, Chifeng City Hospital, Chifeng 024000, China.
Biomed Res Int. 2020 Aug 10;2020:8916729. doi: 10.1155/2020/8916729. eCollection 2020.
AURKA, a cell cycle-regulated kinase, is associated with malignant transformation and progression in many cancer types. We analyzed the expression change of AURKA in pan-cancer and its effect on the prognosis of cancer patients using the TCGA dataset. We revealed that AURKA was extensively elevated and predicted a poor prognosis in most of the detected cancer types, with an exception in colon cancer. AURKA was elevated in colon cancer, but the upregulation of AURKA indicated better outcomes of colon cancer patients. Then we revealed that undermethylation of the AURKA gene and several transcription factors contributed to the upregulation of AURKA in colon cancer. Moreover, we demonstrated that AURKA overexpression promoted the death of colon cancer cells induced by Oxaliplatin, whereas knockdown of AURKA significantly weakened the chemosensitivity of colon cancer cells to Oxaliplatin. Mechanistically, AURKA inhibited DNA damage response by suppressing the expression of various DNA damage repair genes in a TP53-dependent manner, which can partly explain that ARUKA is associated with a beneficial outcome of colon cancer. This study provided a possibility to use AURKA as a biomarker to predict the chemosensitivity of colon cancer to platinum in the clinic.
AURKA 是一种细胞周期调控激酶，与许多癌症类型的恶性转化和进展有关。我们使用 TCGA 数据集分析了 AURKA 在泛癌中的表达变化及其对癌症患者预后的影响。结果表明，AURKA 在大多数检测到的癌症类型中广泛上调，并预测预后不良，但结肠癌除外。AURKA 在结肠癌中上调，但 AURKA 的上调表明结肠癌患者的预后更好。然后我们揭示了 AURKA 基因的低甲基化和几个转录因子有助于结肠癌中 AURKA 的上调。此外，我们证明 AURKA 的过表达促进了奥沙利铂诱导的结肠癌细胞死亡，而 AURKA 的敲低显著削弱了结肠癌细胞对奥沙利铂的化疗敏感性。在机制上，AURKA 通过抑制各种 DNA 损伤修复基因的表达来抑制 DNA 损伤反应，这在一定程度上可以解释 AURKA 与结肠癌有益的结果有关。这项研究为在临床上将 AURKA 用作预测结肠癌对铂类化疗敏感性的生物标志物提供了可能。
