Methylation-Mediated Silencing of RBP7 Promotes Breast Cancer Progression Through PPAR and PI3K/AKT Pathway

Abstract

Purpose Retinoid-binding protein (RBP7) is a member of the cellular retinol-binding protein (CRBP) family, which is involved in the pathogenesis of breast cancer (BRCA). The study aims to illustrate the prognostic value and the potential regulatory mechanisms of RBP7 expression in BRCA. Methods We utilized a series of bioinformatics tools, including HPA, GEPIA, UALCAN, ONCOMINE, Kaplan–Meier plotter, PROGeneV2, TISCH, LinkedOmics, UCSC Xena, MethSurv, SMART APP, bc-GenExMiner4.7, OSbrca, STRING, CARE, SwissDock and R software packages, to investigate the expression, prognostic value and functional regulatory networks of RBP7 in BRCA. Results Bioinformatics analysis with the TCGA and CPTAC databases revealed that the mRNA and protein expression levels of RBP7 in normal were higher compared to BRCA tissues. Survival analysis displayed that the lower expression of RBP7, the worse the prognosis in ER-positive (ER+) BRCA patients. Genomic analysis showed that promoter methylation result in transcriptional silencing of RBP7 in BRCA. Functional enrichment analysis demonstrated that downregulation of RBP7 expression may exert its biological influence on BRCA through the PPAR pathway and the PI3K/AKT pathway. Conclusions In summary, we identified RBP7 as a novel biomarker that is helpful for the prognosis of ER+ BRCA patients. Promoter methylation of RBP7 is involved in its gene silencing in BRCA, thus regulating the occurrence and development of ER+ BRCA through the PPAR and PI3K/AKT pathways.

RBP7 functions as a tumor suppressor in HR+ breast cancer by inhibiting the AKT/SREBP1 pathway and reducing fatty acid

“…Tumor suppressor genes can serve as biomarkers for cancer diagnosis [22] and prognosis [23] and as targets for therapies [21] . Recent studies have explored the value of RBP7 in anticancer [20] and tamoxifen resistance [19] in HR + BC. However, the mechanism of RBP7 in BC remains unknown.…”

“…Reduced expression of RBP7 might lead to resistance to tamoxifen in luminal A breast cancer [19] . A study based on bioinformatics analysis predicted that RBP7 silencing by methylation promoted breast cancer through the PPAR and PI3K/AKT pathways [20] . However, the potential role of RBP7 in breast cancer has not yet been veri ed, and the mechanism remains unknown.…”

Methylation-Mediated Silencing of RBP7 Promotes Breast Cancer Progression through PPAR and PI3K/AKT Pathway

“…We thank the TCGA and GEO network for its generous sharing large amounts of data. The manuscript has been presented as a preprint according to the following link “ https://www.researchsquare.com/article/rs-1135383/v1 ” [ 68 ]. This study was supported by grants from the National Natural Science Foundation of China (No.…”