Background:Microtubule dynamics play a pivotal role in cancer progression and response to chemotherapeutics. Identifying regulators of microtubule stability can provide new therapeutic targets and predictive biomarkers for cancer treatment.Methods:We investigated the role of ARIH1, an E3 ubiquitin ligase, in breast cancer by analyzing clinical datasets to assess its expression levels and prognostic significance. Functional studies were conducted in breast cancer cell lines to evaluate the impact of ARIH1 depletion on microtubule stability, MAP4 regulation, and paclitaxel sensitivity.Results:Clinical dataset analysis revealed that ARIH1 expression is significantly elevated in breast cancer tissues and correlates with poor prognosis and reduced recurrence-free survival. High ARIH1 expression stratifies patients into high-risk groups, underscoring its potential as a prognostic biomarker. Functional studies demonstrated that ARIH1 loss led to upregulation of MAP4, a microtubule-associated protein, resulting in microtubule stabilization via increased tubulin acetylation and enhanced spindle organization. This stabilization sensitized breast cancer cells to paclitaxel treatment, leading to reduced cell viability, impaired colony formation, and increased apoptosis in ARIH1-deficient cells.Conclusions:Our findings identify ARIH1 as a novel regulator of microtubule dynamics in breast cancer. ARIH1 suppression enhances paclitaxel sensitivity, highlighting its potential as both a therapeutic target and a biomarker for predicting treatment response and patient outcomes in breast cancer.
背景：微管动力学在癌症进展及化疗药物反应中起关键作用。识别微管稳定性的调控因子可为癌症治疗提供新的治疗靶点和预测性生物标志物。 方法：通过分析临床数据集评估ARIH1（一种E3泛素连接酶）在乳腺癌中的表达水平及预后意义，探究其作用机制。在乳腺癌细胞系中进行功能研究，评估ARIH1缺失对微管稳定性、MAP4调控及紫杉醇敏感性的影响。 结果：临床数据分析显示，ARIH1在乳腺癌组织中表达显著升高，且与不良预后及无复发生存期缩短相关。高ARIH1表达可将患者划分为高风险群体，提示其作为预后生物标志物的潜力。功能研究表明，ARIH1缺失导致微管相关蛋白MAP4上调，通过增加微管蛋白乙酰化和增强纺锤体组织来稳定微管。这种稳定作用使乳腺癌细胞对紫杉醇治疗更敏感，导致ARIH1缺陷细胞的活力降低、克隆形成能力受损及凋亡增加。 结论：本研究证实ARIH1是乳腺癌微管动力学的新型调控因子。抑制ARIH1可增强紫杉醇敏感性，表明其作为治疗靶点及预测乳腺癌治疗反应和患者预后的生物标志物具有潜在价值。
肿瘤(癌症)患者之家