MiRNA-1915-3p dysregulation characterizes aggressive CRBP1-expressing lung adenocarcinoma cells in vitro and in patient-derived tissues
Year: 2026
Type: article
Abstract: Background Lung adenocarcinoma (LUAD) is the most common histological subtype and a leading cause of cancer mortality worldwide. Cellular Retinol Binding Protein-1 (CRBP1) regulates intracellular retinol bioavailability and several transcriptional activities in normal and neoplastic cells. High CRBP1 expression in LUAD has been previously shown to correlate with worse tumor grade and prognosis. We therefore investigated the putative mechanisms through which CRBP1 expression influences LUAD progression. Methods We analyzed genomic copy number variations, miRNA and gene expression, as well as protein levels and ubiquitination status in CRBP1-transfected A549 cells and in CRBP1-expressing LUAD tissues. Results Bioinformatics analysis revealed that high expression of CRBP1 in both transfected A549 cells and LUAD tissues is associated with miR-1915-3p downregulation. In silico analysis of the interactions between deregulated miR-1915-3p and gene expression identified EGFR and RARα as potential targets. Consistently, western blot analysis confirmed EGFR and RARα upregulation in CRBP1-transfected A549 cells. However, CRBP1-induced EGFR upregulation occurred independently of proteasomal degradation, as no changes in EGFR ubiquitination or protein stability were observed after MG132 treatment. Finally, pathway enrichment analysis revealed that CRBP1 expression is related to the modulation of several genes belonging to cancer pathways. Conclusions Our findings identify a CRBP1-driven molecular landscape characterized by miR-1915-3p suppression and EGFR/RARα upregulation, providing a new hypothetical framework for understanding potential mechanisms of LUAD progression, which requires further validation in larger cohorts.
Source: Frontiers in Oncology
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7225659348