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

Abstract

Retinoid-binding protein7 (RBP7) is a member of the cellular retinol-binding protein (CRBP) family, which is involved in the pathogenesis of breast cancer. The study aims to illustrate the prognostic value and the potential regulatory mechanisms of RBP7 expression in breast cancer. Bioinformatics analysis with the TCGA and CPTAC databases revealed that the mRNA and protein expression levels of RBP7 in normal were higher compared to breast cancer tissues. Survival analysis displayed that the lower expression of RBP7, the worse the prognosis in ER-positive (ER+) breast cancer patients. Genomic analysis showed that low expression of RBP7 correlates with its promoter hypermethylation in breast cancer. Functional enrichment analysis demonstrated that downregulation of RBP7 expression may exert its biological influence on breast cancer through the PPAR pathway and the PI3K/AKT pathway. In summary, we identified RBP7 as a novel biomarker that is helpful for the prognosis of ER+ breast cancer patients. Promoter methylation of RBP7 is involved in its gene silencing in breast cancer, thus regulating the occurrence and development of ER+ breast cancer through the PPAR and PI3K/AKT pathways.

A genome-wide association study reveals novel SNP markers associated with resilience traits in two Mediterranean dairy sheep breeds

“…The latter gene along with ZHX2, DERL1, FAM83A and ATAD2 have been associated with intense symptoms, resistance to chemotherapy and bad prognosis of human breast cancer and metastatic canine mammary adenocarcinomas, implying interference in mammary cell growth and immune regulation (Kalashnikova et al, 2010;Klopfleisch et al, 2010;Lee et al, 2012;Fang et al, 2021;Choi et al, 2022). In accordance with the above, the suggestive significant SNP rs428540973 on chromosome 12, which was associated with SCC in Frizarta sheep, is located within RBP7; downregulation of its expression in human breast cancer has been associated with bad prognosis (Lin et al, 2022). Interestingly, the suggestive SNP for SCC on chromosome 1, rs424064526, is located within the intronic region of FSTL1, which is involved in pathogenetic pathways promoting tissue inflammation and subsequent fibrosis (Andreichenko et al, 2019;Li et al, 2021).…”

Prognostic Value of Histone Acetyl Transferase 1 (HAT-1) and Inflammatory Signatures in Pancreatic Cancer

“…In our study, we have also observed that higher expression levels of these proteins related to HAT-1 (H3/H4, ASF-1, NASP and RBBP7) are directly correlated to a reduced survival, suggesting that this molecular network might represent an important part related to PDAC progression. The relevance of these proteins as prognostic factors for oncological patients has been demonstrated previously [33][34][35][36]. In the event of PDAC, these molecules have been shown to be implicated in a broad molecular network that facilitates pancreatic cancer progression [33,37], which may explain the association of these variables with a poor prognosis.…”