Methylation-associated downregulation of CRABP1 marks an aggressive malignant epithelial cell state in thyroid carcinoma.
4 affiliations
- 1Department of Thyroid Surgery, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, Guangdong, China.
- 2Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, China.
- 3The Fourth General Surgery Department of the Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
- 4Liaoning Fangda General Hospital, Shenyang, Liaoning, China.
Abstract
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, yet molecular features that distinguish indolent tumors from those with progression-associated clinicopathological features remain limited. Here, we integrated single-cell RNA sequencing of 17 PTC samples with copy-number inference and identified a CRABP1-positive malignant epithelial cell population that retained epithelial features (CDH1, KRT19) and exhibited a distinct transcriptional program. In TCGA-THCA bulk data, lower CRABP1 expression was associated with lymph-node metastasis and pathological T-category variation. Functional experiments in complementary thyroid carcinoma cell-line models showed that CRABP1 knockdown increased migration and invasion and was accompanied by an EMT-related transcriptional shift, whereas CRABP1 overexpression showed the opposite pattern. Public methylation analyses showed higher aggregate promoter-region methylation in tumors, whereas methylation of cg02276974, an intron-2/gene-body CpG, was weakly inversely associated with CRABP1 expression (r = -0.2069, R2 = 0.0428; P < 0.001). Decitabine altered migration, invasion, Vimentin-associated, and xenograft phenotypes in CRABP1-manipulated models. Collectively, these results identify a CRABP1-positive malignant epithelial cell state associated with clinicopathological features in PTC and support an invasion-associated suppressive role for CRABP1 in thyroid carcinoma models. The methylation and decitabine findings define a methylation-associated pharmacological context; they do not establish CRABP1-specific or locus-specific epigenetic causality.
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BibTeX
@article{fu2026methylationassociated,
title = {{Methylation-associated downregulation of CRABP1 marks an aggressive malignant epithelial cell state in thyroid carcinoma.}},
author = {Tiancheng Fu and Yudong Li and Guoxiang Huang and Xiarong Hu and Guangfeng Luo and Chengcheng Wang and Yanze Wang and Ziyang Ding and Jinghua Zhou and Zhen Li},
journal = {Frontiers in cell and developmental biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1974822},
url = {https://europepmc.org/article/MED/42952974},
note = {CC BY},
}
RIS
TY - JOUR
TI - Methylation-associated downregulation of CRABP1 marks an aggressive malignant epithelial cell state in thyroid carcinoma.
AU - Tiancheng Fu
AU - Yudong Li
AU - Guoxiang Huang
AU - Xiarong Hu
AU - Guangfeng Luo
AU - Chengcheng Wang
AU - Yanze Wang
AU - Ziyang Ding
AU - Jinghua Zhou
AU - Zhen Li
PY - 2026
DA - 2026/10/14
JO - Frontiers in cell and developmental biology
DO - 10.3389/fcell.2026.1974822
UR - https://europepmc.org/article/MED/42952974
AB - Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, yet molecular features that distinguish indolent tumors from those with progression-associated clinicopathological features remain limited. Here, we integrated single-cell RNA sequencing of 17 PTC samples with copy-number inference and identified a CRABP1-positive malignant epithelial cell population that retained epithelial features (CDH1, KRT19) and exhibited a distinct transcriptional program. In TCGA-THCA bulk data, lower CRABP1 expression was associated with lymph-node metastasis and pathological T-category variation. Functional experiments in complementary thyroid carcinoma cell-line models showed that CRABP1 knockdown increased migration and invasion and was accompanied by an EMT-related transcriptional shift, whereas CRABP1 overexpression showed the opposite pattern. Public methylation analyses showed higher aggregate promoter-region methylation in tumors, whereas methylation of cg02276974, an intron-2/gene-body CpG, was weakly inversely associated with CRABP1 expression (r = -0.2069, R2 = 0.0428; P < 0.001). Decitabine altered migration, invasion, Vimentin-associated, and xenograft phenotypes in CRABP1-manipulated models. Collectively, these results identify a CRABP1-positive malignant epithelial cell state associated with clinicopathological features in PTC and support an invasion-associated suppressive role for CRABP1 in thyroid carcinoma models. The methylation and decitabine findings define a methylation-associated pharmacological context; they do not establish CRABP1-specific or locus-specific epigenetic causality.
SN - 2296-634X
ER -