PUBLICATION
Exploring the tumor suppressor role of RIN1 in familial thyroid carcinoma
- Authors
- Picello, L., Dalle Nogare, M., Puggina, D., Salvoro, C., Pennelli, G., Gaudenzi, G., Carra, S., Oldani, M., Gentilini, D., Fugazzola, L., Faggiano, A., Vitale, G., Occhi, G., Vazza, G.
- ID
- ZDB-PUB-250322-8
- Date
- 2025
- Source
- Endocrine-related cancer : (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Zebrafish
- Humans
- Male
- Intracellular Signaling Peptides and Proteins*/genetics
- Intracellular Signaling Peptides and Proteins*/metabolism
- Thyroid Neoplasms*/genetics
- Thyroid Neoplasms*/metabolism
- Thyroid Neoplasms*/pathology
- Cell Line, Tumor
- Female
- Genes, Tumor Suppressor
- Middle Aged
- Adult
- Animals
- PubMed
- 40116813 Full text @ Endocr. Relat. Cancer
Citation
Picello, L., Dalle Nogare, M., Puggina, D., Salvoro, C., Pennelli, G., Gaudenzi, G., Carra, S., Oldani, M., Gentilini, D., Fugazzola, L., Faggiano, A., Vitale, G., Occhi, G., Vazza, G. (2025) Exploring the tumor suppressor role of RIN1 in familial thyroid carcinoma. Endocrine-related cancer. :.
Abstract
The genetic component is thought to play an important role in the development of familial non-medullary thyroid carcinoma (fNMTC), but the involved molecular mechanisms and genes are poorly understood. The MAPK kinase cascade, particularly involving RAS and BRAF, is crucial in cancer development, with RIN1 emerging as a notable gene due to its differential expression across various tumor types. We identified a frameshift mutation (c.798delC: p.V267Sfs*83) in the RIN1 gene in a family with non-medullary thyroid cancer (NMTC) through Whole-Exome Sequencing. Paraffin-embedded tumor tissues were analyzed to investigate the mutation's characteristics and its potential implications within the thyroid cellular context. Functional assays and RNA sequencing using CRISPR/Cas9-edited Nthy-ori 3-1 thyroid cell line and xenograft zebrafish models confirmed the mutation effect and the putative RIN1 tumor suppressor role. The study revealed significant alterations in cellular behavior upon RIN1 knockout, including increased cell viability, proliferation, and colony formation, alongside morphological changes indicative of epithelial-mesenchymal transition. Enhanced phosphorylation of ERK and AKT suggested MAPK pathway dysregulation following RIN1 depletion, supporting its potential tumor suppressive role. Phenotypic rescue experiments confirmed that reintroduction of wild-type RIN1 restored normal cellular behavior. RNA sequencing demonstrated differential gene expression between RIN1-/- and control cells, particularly affecting pathways associated with cancer progression, closely resembled signatures specific to NMTC. This study provides compelling evidence supporting RIN1 as a tumor suppressor gene within thyroid cells. Additionally, the findings highlight its potential significance as novel gene involved in FNMTC pathogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping