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Updated: Apr 19, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
The cl2/dro1/ccdc80 null mice develop thyroid and ovarian neoplasias
Vincenza Leone1, Angelo Ferraro1, Filippo Schepis2
1Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS) "G. Salvatore", Consiglio Nazionale delle Ricerche (CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Università degli Studi di Napoli "Federico II", Via S. Pansini 5, Naples 80131, Italy.
Abstract:
We have previously reported that the expression of the CL2/CCDC80 gene is downregulated in human papillary thyroid carcinomas, particularly in follicular variants. We have also reported that the restoration of CL2/CCDC80 expression reverted the malignant phenotype of thyroid carcinoma cell lines and that CL2/CCDC80 positively regulated E-cadherin expression, an ability that likely accounts for the role of the CL2/CCDC80 gene in thyroid cancer progression. In order to validate the tumour suppressor role of the CL2/CCDC80 gene in thyroid carcinogenesis we generated cl2/ccdc80 knock-out mice. We found that embryonic fibroblasts from cl2/ccdc80(-/-) mice showed higher proliferation rate and lower susceptibility to apoptosis. Furthermore, cl2/ccdc80(-/-) mice developed thyroid adenomas and ovarian carcinomas. Finally, ret/PTC1 transgenic mice crossed with the cl2/ccdc80 knock-out mice developed more aggressive thyroid carcinomas compared with those observed in the single ret/PTC1 transgenic mice. Together, these results indicate CL2/CCDC80 as a putative tumour suppressor gene in human thyroid carcinogenesis.
Insights
The CL2/CCDC80 gene acts as a tumor suppressor in thyroid cancer. Its absence leads to increased cell proliferation and tumor development, validating its role in preventing thyroid carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- CL2/CCDC80 gene expression is reduced in human papillary thyroid carcinomas.
- Restoring CL2/CCDC80 expression reverses malignant phenotypes and upregulates E-cadherin.
- CL2/CCDC80's role in thyroid cancer progression is linked to E-cadherin regulation.
Purpose of the Study:
- To validate the tumor suppressor role of the CL2/CCDC80 gene in thyroid carcinogenesis.
- To investigate the in vivo effects of CL2/CCDC80 deficiency on tumor development.
Main Methods:
- Generation of CL2/CCDC80 knock-out (KO) mice.
- Analysis of embryonic fibroblasts from CL2/CCDC80(-/-) mice.
- Development of thyroid and ovarian tumors in CL2/CCDC80 KO mice.
- Cross-breeding CL2/CCDC80 KO mice with ret/PTC1 transgenic mice.
Main Results:
- CL2/CCDC80(-/-) embryonic fibroblasts exhibit increased proliferation and reduced apoptosis.
- CL2/CCDC80 KO mice develop thyroid adenomas and ovarian carcinomas.
- Combined CL2/CCDC80 deficiency and ret/PTC1 expression result in more aggressive thyroid carcinomas.
Conclusions:
- CL2/CCDC80 functions as a tumor suppressor gene in human thyroid carcinogenesis.
- The absence of CL2/CCDC80 promotes tumor initiation and progression.
- CL2/CCDC80 is a critical factor in regulating thyroid cancer aggressiveness.
