Yilun Li, Baifang Ding, Mengyu Wei, Xiaolu Yang, Ruihuan Fu, Yinfeng Liu, Lin Zhu, Yan Ding, Wenjin Zhang, Geng Zhang, Shuo Zhang, Yuhui Bu, Jianchao He, Jianye Deng, Xiaohuan Bao, Jun Hao, Li Ma
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引用次数: 0
Abstract
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 (ERα) and up-regulation of ER beta (ERβ) 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 ERα and ERβ. 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.
期刊介绍：
Asia–Pacific Journal of Clinical Oncology is a multidisciplinary journal of oncology that aims to be a forum for facilitating collaboration and exchanging information on what is happening in different countries of the Asia–Pacific region in relation to cancer treatment and care. The Journal is ideally positioned to receive publications that deal with diversity in cancer behavior, management and outcome related to ethnic, cultural, economic and other differences between populations. In addition to original articles, the Journal publishes reviews, editorials, letters to the Editor and short communications. Case reports are generally not considered for publication, only exceptional papers in which Editors find extraordinary oncological value may be considered for review. The Journal encourages clinical studies, particularly prospectively designed clinical trials.
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