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Tumor suppression by MEG3 lncRNA in a human pituitary tumor derived cell line.

Abstract
Human clinically non-functioning pituitary adenomas (NFAs) account for approximately 40% of diagnosed pituitary tumors. Epigenetic mutations in tumor suppressive genes play an important role in NFA development. Maternally expressed gene 3 (MEG3) is a long non-coding RNA (lncRNA) and we hypothesized that it is a candidate tumor suppressor whose epigenetic silencing is specifically linked to NFA development. In this study, we introduced MEG3 expression into PDFS cells, derived from a human NFA, using both inducible and constitutively active expression systems. MEG3 expression significantly suppressed xenograft tumor growth in vivo in nude mice. When induced in culture, MEG3 caused cell cycle arrest at the G1 phase. In addition, inactivation of p53 completely abolished tumor suppression by MEG3, indicating that MEG3 tumor suppression is mediated by p53. In conclusion, our data support the hypothesis that MEG3 is a lncRNA tumor suppressor in the pituitary and its inactivation contributes to NFA development.
AuthorsPaweena Chunharojrith, Yuki Nakayama, Xiaobing Jiang, Rachel E Kery, Jun Ma, Cristine S De La Hoz Ulloa, Xun Zhang, Yunli Zhou, Anne Klibanski
JournalMolecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 416 Pg. 27-35 (Nov 15 2015) ISSN: 1872-8057 [Electronic] Ireland
PMID26284494 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • MEG3 non-coding RNA, human
  • RNA, Long Noncoding
  • Tumor Suppressor Protein p53
Topics
  • Acetylation
  • Animals
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Epigenesis, Genetic
  • Female
  • G1 Phase
  • Genes, Tumor Suppressor
  • Heterografts
  • Humans
  • Mice
  • Mice, Nude
  • Pituitary Gland (metabolism)
  • Pituitary Neoplasms (genetics)
  • Primary Cell Culture
  • RNA, Long Noncoding (genetics, metabolism)
  • Tumor Suppressor Protein p53 (metabolism)

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