MiRNA-1915-3p dysregulation characterizes aggressive CRBP1-expressing lung adenocarcinoma cells in vitro and in patient-derived tissues
4 affiliations
- 1Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome
- 2UniCamillus-Saint Camillus International University of Health Sciences
- 3Anatomic Pathology, Department of Integrated Care Processes, Policlinico Tor Vergata
- 4Department of Biomedical Sciences, Catholic University Our Lady of Good Counsel
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.
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BibTeX
@article{ferlosio2026mirna19153p,
title = {{MiRNA-1915-3p dysregulation characterizes aggressive CRBP1-expressing lung adenocarcinoma cells in vitro and in patient-derived tissues}},
author = {Amedeo Ferlosio and Federica Centofanti and Elena Doldo and Tonia Cenci and Manjola Qordja and Maria Cristina Rapanotti and Maria Giovanna Scioli and Augusto Orlandi},
journal = {Frontiers in Oncology},
year = {2026},
month = nov,
doi = {10.3389/fonc.2026.1983972},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1983972/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - MiRNA-1915-3p dysregulation characterizes aggressive CRBP1-expressing lung adenocarcinoma cells in vitro and in patient-derived tissues
AU - Amedeo Ferlosio
AU - Federica Centofanti
AU - Elena Doldo
AU - Tonia Cenci
AU - Manjola Qordja
AU - Maria Cristina Rapanotti
AU - Maria Giovanna Scioli
AU - Augusto Orlandi
PY - 2026
DA - 2026/11/09
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1983972
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1983972/full
AB - 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.
SN - 2234-943X
ER -