Identification of a novel noncoding RNA gene, NAMA, that is downregulated in papillary thyroid carcinoma with BRAF mutation and associated with growth arrest

Heejei Yoon, Huiling He, Rebecca Nagy, Ramana Davuluri, Saul Suster, Daniel Schoenberg, Natalia Pellegata, Albert De La Chapelle*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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 ∼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.

Original languageEnglish (US)
Pages (from-to)767-775
Number of pages9
JournalInternational Journal of Cancer
Volume121
Issue number4
DOIs
StatePublished - Aug 15 2007

Keywords

  • BRAF
  • Growth arrest
  • NAMA
  • Noncoding RNA
  • Papillary thyroid carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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