Back to Search
Start Over
The PDCD4/miR-21 pathway in medullary thyroid carcinoma.
- Source :
-
Human pathology [Hum Pathol] 2015 Jan; Vol. 46 (1), pp. 50-7. Date of Electronic Publication: 2014 Oct 02. - Publication Year :
- 2015
-
Abstract
- Programmed cell death 4 (PDCD4) is a tumor suppressor gene involved in tumorogenesis. MicroRNA-21 (miR-21) specifically targets PDCD4, and recent studies suggest that PDCD4 is also regulated by Akt (antiapoptotic regulator within phosphatidylinositol 3-kinase). Medullary thyroid carcinoma (MTC) is a rare neuroendocrine cancer, and disease stage at diagnosis represents the main prognostic indicator. A consecutive series of 64 MTCs was considered. REarranged during Transfection (RET) and rat sarcoma (RAS) mutation status was assessed by direct sequencing. Quantitative real-time polymerase chain reaction was used to quantify mature hsa-miR-21. PDCD4 and Ki-67 immunostaining was performed with an automated platform. Immunoblot analysis of PI3K/Akt pathway was done on thyroid tissues. MTCs were consistently associated with miR-21 up-regulation (P < .0016) and featured significant PDCD4 nuclear down-regulation. An inverse correlation emerged between miR-21 overexpression and PDCD4 down-regulation (P = .0013). At enrollment, high miR-21 levels were associated with high calcitonin levels (P = .0003), lymph node metastases (P = .001), and advanced stages (P = .0003). At the end of follow-up, high miR-21 levels were associated with biochemically persistent disease (P = .0076). At enrollment, instead, PDCD4 nuclear down-regulation was associated with high calcitonin levels (P = .04), more advanced stages of disease (P < .01), and persistent disease after the follow-up (P = .02). p-Akt was more expressed in RAS-mutated MTC than in nonmutated cancers and normal tissue. This study showed, in MTCs, that miR-21 regulates PDCD4 expression and also that the miR-21/PDCD4 pathway correlates with clinicopathological variables and prognosis. Further studies should investigate the role of miR-21 as a prognostic biomarker and the feasibility of using PDCD4-restoring strategies as a therapeutic approach to MTC.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Biomarkers, Tumor blood
Biopsy
Calcitonin blood
Carcinoma, Neuroendocrine
Child
Child, Preschool
DNA Mutational Analysis
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
Genetic Predisposition to Disease
Humans
Immunohistochemistry
Ki-67 Antigen analysis
Male
Middle Aged
Mutation
Neoplasm Staging
Phenotype
Phosphorylation
Proto-Oncogene Proteins c-akt analysis
Proto-Oncogene Proteins c-ret genetics
Real-Time Polymerase Chain Reaction
Retrospective Studies
Thyroid Neoplasms blood
Thyroid Neoplasms mortality
Thyroid Neoplasms pathology
Up-Regulation
Young Adult
ras Proteins genetics
Apoptosis Regulatory Proteins analysis
Biomarkers, Tumor analysis
Biomarkers, Tumor genetics
MicroRNAs genetics
RNA-Binding Proteins analysis
Signal Transduction
Thyroid Neoplasms chemistry
Thyroid Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1532-8392
- Volume :
- 46
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Human pathology
- Publication Type :
- Academic Journal
- Accession number :
- 25316501
- Full Text :
- https://doi.org/10.1016/j.humpath.2014.09.006