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Identification of a novel noncoding RNA gene, NAMA, that is downregulated in papillary thyroid carcinoma with BRAF
Heejei Yoon1, Huiling He, Rebecca Nagy
1Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. albert.delachapelle@osumc.edu
Abstract:
In search of tumor suppressor genes in papillary thyroid carcinoma (PTC), we previously used gene expression profiling to identify genes underexpressed in tumor compared with paired unaffected tissue. While searching for loss of heterozygosity (LOH) in genomic regions harboring candidate tumor suppressor genes, we detected LOH in a approximately 20 kb region around marker D9S176. Several ESTs flanking D9S176 were underexpressed in PTC tumors, and for one of the ESTs, downregulation was highly associated with the activating BRAF mutation V600E, the most common genetic lesion in PTC. A novel gene, NAMA, (noncoding RNA associated with MAP kinase pathway and growth arrest) containing the affected EST was cloned and characterized. NAMA is weakly expressed in several human tissues, and the spliced forms are primarily detected in testis. Several characteristics of NAMA suggest that it is a nonprotein coding but functional RNA; it has no long open reading frames (ORFs); the exons exhibit low sequence identity in the evolutionarily conserved regions; it is inducible by knockdown of BRAF, inhibition of the MAP kinase pathway, growth arrest and DNA damage in cancer cell lines. We suggest that NAMA is a noncoding RNA associated with growth arrest.
Insights
Researchers identified a novel noncoding RNA, NAMA, in papillary thyroid carcinoma (PTC). NAMA downregulation correlates with BRAF mutations and is linked to growth arrest, suggesting its role in PTC development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy.
- Identifying tumor suppressor genes is crucial for understanding PTC pathogenesis.
- The BRAF V600E mutation is a frequent genetic driver in PTC.
Purpose of the Study:
- To identify novel tumor suppressor genes in papillary thyroid carcinoma.
- To characterize a newly discovered gene, NAMA, and its potential role in PTC.
Main Methods:
- Gene expression profiling to identify underexpressed genes in PTC.
- Loss of heterozygosity (LOH) analysis to detect genomic alterations.
- Cloning and characterization of the novel gene NAMA.
- Functional studies involving gene knockdown and pathway inhibition in cancer cell lines.
Main Results:
- LOH was detected in a region containing ESTs underexpressed in PTC.
- A novel noncoding RNA gene, NAMA, was identified and cloned.
- NAMA expression is downregulated in PTC and associated with BRAF V600E mutation.
- NAMA is inducible by BRAF knockdown, MAP kinase inhibition, growth arrest, and DNA damage.
Conclusions:
- NAMA is a novel noncoding RNA potentially involved in tumor suppression.
- NAMA's regulation by MAP kinase pathway and its association with growth arrest suggest a role in PTC development.
- Further investigation into NAMA's function could offer new therapeutic targets for PTC.
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