目的：疤痕疙瘩是良性纤维增生性疾病，侵袭性生长超过伤口边界。极光激酶A（AURKA）是一种在多种肿瘤中高表达的丝氨酸/苏氨酸激酶，促进肿瘤生长和侵袭。目前，AURKA 在疤痕疙瘩中的作用仍不清楚。方法：从疤痕疙瘩和正常皮肤样本中分离出成纤维细胞。通过 qPCR、蛋白质印迹和免疫组织化学评估 AURKA。应用转录组测序和双荧光素酶报告基因测定来找出 AURKA 的靶点。在表达改变和 MLN8237（一种 AURKA 激酶抑制剂，AKI）治疗后，进行表型实验以阐明 AURKA 及其靶点的生物学功能，并探讨 AURKA 抑制的临床潜力。结果：AURKA 在疤痕组织和成纤维细胞中表达上调。 Forkhead box O 3a (FOXO3a) 被验证为 AURKA 的下游。进一步的实验表明，AURKA 通过与 FOXO3a 结合来反式激活 FOXO3a，而 FOXO3a 则直接反式激活 AURKA。在功能上，AURKA 和 FOXO3a 通过蛋白激酶 B (AKT) 磷酸化协同增强瘢痕疙瘩成纤维细胞的增殖和迁移。尽管 MLN8237 削弱了瘢痕疙瘩成纤维细胞的增殖和迁移，但 AURKA 对 FOXO3a 的反式激活与激酶活性无关。创新：这项研究揭示了 AURKA 和 FOXO3a 组成了一个反式激活环，可增强瘢痕疙瘩成纤维细胞的增殖和迁移特性，并提出 AURKA 作为一个有前途的靶点。结论：AURKA/FOXO3a环通过AKT信号促进瘢痕疙瘩成纤维细胞的增殖和迁移。尽管 AKI 具有抗瘢痕疙瘩作用，但 AURKA 作为独立于激酶活性的转录因子发挥作用，加深了我们对 AKI 不敏感性的理解。

Objective: Keloids are benign fibroproliferative disorders with invasive growth exceeding the wound boundary. Aurora kinase A (AURKA) is a serine/threonine kinase highly expressed in various tumors, facilitating tumor growth and invasion. Currently, the role of AURKA in keloid remains unclear. Approach: Fibroblasts were isolated from keloid and normal skin samples. AURKA was evaluated by qPCR, Western blot, and immunohistochemistry. Transcriptome sequencing and dual-luciferase reporter assays were applied to figure out targets of AURKA. Following expression alteration and MLN8237 (an AURKA kinase inhibitor, AKI) treatment, phenotypical experiments were conducted to clarify biological functions of AURKA along with its target, and to probe into the clinical potential of AURKA inhibition. Results: AURKA was upregulated in keloid tissues and fibroblasts. Forkhead box O 3a (FOXO3a) was verified as a downstream of AURKA. Further experiments demonstrated that AURKA transactivated FOXO3a by binding to FOXO3a, while FOXO3a directly transactivated AURKA. Functionally, AURKA and FOXO3a cooperated in enhancing the proliferation and migration of keloid fibroblasts via protein kinase B (AKT) phosphorylation. Although MLN8237 weakened the proliferation and migration in keloid fibroblasts, the transactivation of AURKA on FOXO3a was independent of kinase activity. Innovation: This study reveals that AURKA and FOXO3a compose a transactivation loop in enhancing the proliferative and migrative properties of keloid fibroblasts, and proposes AURKA as a promising target. Conclusion: AURKA/FOXO3a loop promotes the proliferation and migration of keloid fibroblasts via AKT signaling. Despite the anti-keloid effects of AKIs, AURKA acts as a transcription factor independently of kinase activity, deepening our understanding on AKI insensitivity.