Liu Yan, Wen Yue, Nie Ziyuan, Jia Li
Department of Anesthesiology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Department of Ultrasound, The Fourth Hospital of Hebei Medical University Hebei, Shijiazhuang, 050000, Hebei, China.
J Cancer. 2025 Jan 13;16(4):1215-1227. doi: 10.7150/jca.103134. eCollection 2025.
In recent years, aurora kinase C (AURKC) has emerged as a potential therapeutic target for cancer, having been found to induce proliferation in a variety of cancers. However, at present, its precise mechanism remains unclear. In this study, the specific role of AURKC in renal clear cell carcinoma and its mechanism was investigated. The protein expression levels of AURKC were evaluated in clear cell carcinoma and adjacent normal tissues, followed by prognostic analysis. Subsequently, cell models with knocked-down and overexpressed AURKC were constructed for cell experiments, and tumor-bearing mouse models were constructed to confirm the specific role of AURKC . AURKC was found to be highly expressed in ccRCC, which was associated with poor prognosis. In the experiments, the expression levels of CyclinD1 and proliferating cell nuclear antigen (PCNA) proteins were downregulated after AURKC knockdown, and the cell proliferation ability was found to decrease significantly. After AURKC overexpression, the levels of ERp57 protein expression increased significantly, also significantly enhancing the cell proliferation ability. In addition, AURKC was found to interact with ERp57 and exhibited a colocalization relationship. In the experiments, AURKC downregulation significantly inhibited the expression of ERp57 protein and blocked the growth of tumor tissue in tumor-bearing mice. These results suggest that the abnormal expression of AURKC in ccRCC enhances the expression of ERp57 protein, thereby promoting the proliferation of clear cell renal cell carcinoma. Thus, AURKC shows potential as a target for the treatment of ccRCC.
近年来，极光激酶C（AURKC）已成为一种潜在的癌症治疗靶点，已发现它能在多种癌症中诱导细胞增殖。然而，目前其确切机制仍不清楚。在本研究中，我们研究了AURKC在肾透明细胞癌中的具体作用及其机制。评估了AURKC在透明细胞癌及癌旁正常组织中的蛋白表达水平，随后进行预后分析。随后，构建了AURKC敲低和过表达的细胞模型用于细胞实验，并构建了荷瘤小鼠模型以证实AURKC的具体作用。发现AURKC在肾透明细胞癌中高表达，这与不良预后相关。在实验中，AURKC敲低后细胞周期蛋白D1（CyclinD1）和增殖细胞核抗原（PCNA）蛋白的表达水平下调，且细胞增殖能力显著降低。AURKC过表达后，内质网蛋白57（ERp57）蛋白表达水平显著升高，细胞增殖能力也显著增强。此外，发现AURKC与ERp57相互作用并呈现共定位关系。在实验中，AURKC下调显著抑制ERp57蛋白表达，并抑制荷瘤小鼠肿瘤组织的生长。这些结果表明，肾透明细胞癌中AURKC的异常表达增强了ERp57蛋白的表达，从而促进了肾透明细胞癌的增殖。因此，AURKC显示出作为肾透明细胞癌治疗靶点的潜力。
