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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1517226

Aurora kinase A promotes hepatic stellate cell activation and liver fibrosis through the Wnt/β-catenin pathway

Provisionally accepted
Guanqi Dai Guanqi Dai 1Lin Junhao Lin Junhao 1Yuchuan Jiang Yuchuan Jiang 2Xinhui Liu Xinhui Liu 1Peng Chen Peng Chen 3Yixiao Zhang Yixiao Zhang 1Zhenhui Song Zhenhui Song 1Xuefen Zhuang Xuefen Zhuang 1jinge Cong jinge Cong 1yingchun li yingchun li 1Xuanjia Hong Xuanjia Hong 1,4Yun Liu Yun Liu 1,4Dong Xiao Dong Xiao 1*Aimin Li Aimin Li 1,4*Yue Luo Yue Luo 1*
  • 1 Southern Medical University, Guangzhou, Guangdong, China
  • 2 The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
  • 3 Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
  • 4 Southern Medical University, Guangzhou, 510315, China, Guangzhou, China

The final, formatted version of the article will be published soon.

    Aims: Aurora kinase A (AURKA) has been implicated in promoting myeloid and renal fibrosis. This study aimed to investigate the impact and underlying mechanism of AURKA on liver fibrosis and to assess the therapeutic potential of MLN8237, a small-molecule AURKA inhibitor, in preventing liver fibrosis in mice.The research used bioinformatics analysis and immunohistochemistry staining on fibrotic liver tissues from human and mouse models to assess AURKA expression.The cellular localization of AURKA was determined through double immunofluorescence staining in human fibrotic liver tissues and primary mouse hepatic stellate cells. RNA interference and AURKA antagonism were used to examine the effects of AURKA on liver fibrosis, while RNA-sequencing, qRT-PCR, and western blotting were employed to elucidate the potential molecular mechanisms of AURKA on hepatic stellate cell activation.The results showed that AURKA was positively correlated with the progression of liver fibrosis and was predominantly expressed in activated HSCs. Silencing AURKA inhibited HSC activation and proliferation, and induced HSC apoptosis, effects that were similar to those observed with MLN8237 treatment. Additionally, silencing AURKA suppressed the glycogen synthase kinase-3β/β-catenin signaling pathway.Pharmacological inhibition of AURKA phosphorylation also resulted in reduced liver fibrosis in vivo.In conclusion, AURKA may promote HSC activation and liver fibrosis through the Wnt/β-catenin pathway, suggesting its potential as a therapeutic target for liver fibrosis.

    Keywords: Aurora Kinase A, Hepatic Stellate Cells, liver fibrosis, MLN8237, Wnt/β-Catenin pathway

    Received: 25 Oct 2024; Accepted: 06 Dec 2024.

    Copyright: © 2024 Dai, Junhao, Jiang, Liu, Chen, Zhang, Song, Zhuang, Cong, li, Hong, Liu, Xiao, Li and Luo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Dong Xiao, Southern Medical University, Guangzhou, 510515, Guangdong, China
    Aimin Li, Southern Medical University, Guangzhou, 510315, China, Guangzhou, China
    Yue Luo, Southern Medical University, Guangzhou, 510515, Guangdong, China

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