Tumor suppression by MEG3 lncRNA in a human pituitary tumor derived cell line.
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.
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Paweena
P
Chunharojrith
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Yuki
Y
Nakayama
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Xiaobing
X
Jiang
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Rachel E
RE
Kery
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Jun
J
Ma
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Cristine S
CS
De La Hoz Ulloa
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Xun
X
Zhang
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: yunli.zhou@mgh.harvard.edu.
Yunli
Y
Zhou
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Anne
A
Klibanski
D000107:Acetylation; D000818:Animals; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic; D005260:Female; D016193:G1 Phase; D016147:Genes, Tumor Suppressor; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010902:Pituitary Gland / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000235:genetics*; D061251:Primary Cell Culture; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C498907:MEG3 non-coding RNA, human; D062085:RNA, Long Noncoding; D016159:Tumor Suppressor Protein p53
Long non-coding RNA; MEG3; Pituitary tumor; Tumor suppression; p53