The prognostic and immune significance of Rab11A in pan-cancer and its function and mechanism underlying estrogen receptor targeting in breast cancer

被引:0
作者
Li, Yilun [1 ]
Ding, Baifang [2 ]
Wei, Mengyu [1 ]
Yang, Xiaolu [1 ]
Fu, Ruihuan [1 ]
Liu, Yinfeng [1 ]
Zhu, Lin [3 ]
Ding, Yan [5 ]
Zhang, Wenjin [1 ]
Zhang, Geng [1 ]
Zhang, Shuo [1 ]
Bu, Yuhui [1 ]
He, Jianchao [1 ]
Deng, Jianye [1 ]
Bao, Xiaohuan [1 ]
Hao, Jun [4 ]
Ma, Li [1 ]
机构
[1] Hebei Med Univ, Dept Breast Dis Ctr, Hosp 4, 169 Tianshan St, Shijiazhuang 050035, Peoples R China
[2] Panjin Cent Hosp, Dept Breast Surg, Panjin, Peoples R China
[3] Hebei Med Univ, Hosp 3, Dept Electromyogram, Shijiazhuang, Peoples R China
[4] Hebei Med Univ, Dept Pathol, 361 Zhongshan East Rd, Shijiazhuang 050017, Peoples R China
[5] Hebei Med Univ, Hosp 4, Dept Pathol, Shijiazhuang, Peoples R China
基金
中国国家自然科学基金;
关键词
ER; immune characteristics; pan-cancer; prognosis; Rab11A; PROLIFERATION; CELLS; EXPRESSION; MOTILITY; GTPASES; GENE;
D O I
10.1111/ajco.14130
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objective Rab11A is an important molecule for recycling endosomes and is closely related to the proliferation, invasion, and metastasis of tumors. This study investigated the prognostic and immune significance of Rab11A and validated its potential function and mechanism in breast cancer (BRCA). Methods RNA sequencing data for 33 tumors were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression databases. Correlation analysis was used to evaluate the relationship between Rab11A expression and immune characteristics. Potential pathways were identified using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis. Immunohistochemical analysis, colony formation assay, bromodeoxyuridine incorporation assay, immunofluorescence, and Western blot were used to explore potential function and mechanism. Results Analysis of the TCGA database showed significant upregulation of Rab11A expression in a variety of cancers. Rab11A was up-regulated in 82.4% of BRCA. High Rab11A expression is associated with poor survival in cancer patients and is a predictor of poor prognosis. CIBERSORT analysis showed that Rab11A was negatively associated with almost all immune cycle activity scores pan-cancer. The results of the TCGA-BRCA cohort were further confirmed by using pathological samples from clinical BRCA patients. The results showed that Rab11A expression was correlated with estrogen receptor (ER) and progesterone receptor expression in BRCA (p < 0.05). Knockdown and overexpression of Rab11A affected the proliferation of BRCA cells. Further mechanistic studies revealed that down-regulation of ER alpha (ER alpha) and up-regulation of ER beta (ER beta) mediated Rab11A-induced inhibition of BRCA cell proliferation. Conclusion Rab11A expression in pan-cancer is associated with poor prognosis and immune profile. In particular, in BRCA, Rab11A expression regulates cell proliferation by targeting ER alpha and ER beta. High Rab11A expression is tightly associated with immune characteristics, tumor microenvironment, and genetic mutations. These results provide a reference for exploring the role of Rab11A in pan-cancer and provide a new perspective for revealing potential therapeutic targets in BRCA.
引用
收藏
页码:12 / 30
页数:19
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