Annexin A1 promotes the progression of bladder cancer via regulating EGFR signaling pathway.
Annexin A1 promotes the progression of bladder cancer via regulating EGFR signaling pathway.
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annexin A1通过调节EGFR信号通路促进膀胱癌进展
DOI：
10.1186/s12935-021-02427-4
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发表时间：
2022-01-06
影响因子：
5.8
通讯作者：
Xia S
中科院分区：
文献类型：
--
作者：
Li P;Li L;Li Z;Wang S;Li R;Zhao W;Feng Y;Huang S;Li L;Qiu H;Xia S
背景膀胱癌（BLCA）是全世界最常见的恶性肿瘤之一。 BLCA管理不理想的主要原因之一是其复杂的分子生物学机制。膜联蛋白 A1 (ANXA1) 是一种 Ca2+ 调节的磷脂结合蛋白，已被证明与许多癌症的进展和预后有关。然而，ANXA1在BLCA中的表达模式、生物学功能和机制仍不清楚。方法基于TCGA和GEO数据集，通过生物信息学分析探讨ANXA1在BLCA中的临床相关性。免疫组织化学（IHC）分析检测BLCA组织中ANXA1的表达，并分析ANXA1与临床参数的关系。通过体外和体内实验来研究ANXA1在BLCA中的生物学功能。最后，通过生物信息学分析探讨ANXA1在BLCA中的潜在机制，并通过体外和体内实验进行验证。结果生物信息学和IHC分析表明ANXA1的高表达水平与BLCA患者的病情进展和不良预后密切相关。功能研究表明，ANXA1沉默可在体外抑制BLCA细胞的增殖、迁移、侵袭和上皮间质转化（EMT），并在体内抑制异种移植膀胱肿瘤的生长。从机制上讲，ANXA1 的缺失会降低 EGFR 的表达和磷酸化水平以及下游信号通路的激活。此外，ANXA1 的敲低加速了 P-EGFR 的泛素化和降解，从而下调 EGFR 信号传导的激活。结论这些发现表明，ANXA1 是 BLCA 预后的可靠临床预测因子，并通过激活 BLCA 中的 EGFR 信号传导促进增殖和迁移。因此，ANXA1可能成为BLCA患者预后的一个有前景的生物标志物，从而为未来BLCA的精准和个性化治疗提供线索。
BackgroundBladder cancer (BLCA) is one of the most common malignancies worldwide. One of the main reasons for the unsatisfactory management of BLCA is the complex molecular biological mechanism. Annexin A1 (ANXA1), a Ca2+-regulated phospholipid-binding protein, has been demonstrated to be implicated in the progression and prognosis of many cancers. However, the expression pattern, biological function and mechanism of ANXA1 in BLCA remain unclear.MethodsThe clinical relevance of ANXA1 in BLCA was investigated by bioinformatics analysis based on TCGA and GEO datasets. Immunohistochemical (IHC) analysis was performed to detect the expression of ANXA1 in BLCA tissues, and the relationships between ANXA1 and clinical parameters were analyzed. In vitro and in vivo experiments were conducted to study the biological functions of ANXA1 in BLCA. Finally, the potential mechanism of ANXA1 in BLCA was explored by bioinformatics analysis and verified by in vitro and in vivo experiments.ResultsBioinformatics and IHC analyses indicated that a high expression level of ANXA1 was strongly associated with the progression and poor prognosis of patients with BLCA. Functional studies demonstrated thatANXA1silencing inhibited the proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) of BLCA cells in vitro, and suppressed the growth of xenografted bladder tumors in vivo. Mechanistically, loss ofANXA1decreased the expression and phosphorylation level of EGFR and the activation of downstream signaling pathways. In addition, knockdown ofANXA1accelerated ubiquitination and degradation of P-EGFR to downregulate the activation of EGFR signaling.ConclusionsThese findings indicate that ANXA1 is a reliable clinical predictor for the prognosis of BLCA and promotes proliferation and migration by activating EGFR signaling in BLCA. Therefore, ANXA1 may be a promising biomarker for the prognosis of patients with BLCA, thus shedding light on precise and personalized therapy for BLCA in the future.
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影响因子：
8.8
作者：
Duncan, R.;Carpenter, B.;Main, L. C.;Telfer, C.;Murray, G. I.
通讯作者：
Murray, G. I.
影响因子：
4.5
作者：
Li, Chien-Feng;Shen, Kun-Hung;Wu, Ting-Feng
通讯作者：
Wu, Ting-Feng
影响因子：
5.4
作者：
Han G;Lu K;Huang J;Ye J;Dai S;Ye Y;Zhang L
通讯作者：
Zhang L
影响因子：
4.4
作者：
Li, Piao;Huang, Tingting;Qiu, Hong
通讯作者：
Qiu, Hong
影响因子：
5.2
作者：
Alessio, Nicola;Aprile, Domenico;Galderisi, Umberto
通讯作者：
Galderisi, Umberto