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Functional characterization of DLK1/MEG3 locus on chromosome 14q32.2 reveals the differentiation of pituitary neuroendocrine tumors.


ABSTRACT: Pituitary neuroendocrine tumors (PitNETs) represent the neoplastic proliferation of the anterior pituitary gland. Transcription factors play a key role in the differentiation of PitNETs. However, for a substantial proportion of PitNETs, the etiology is poorly understood. According to the transcription data of 172 patients, we found the imprinting disorders of the 14q32.2 region and DLK1/MEG3 locus associated with the differentiation of PitNETs. DLK1/MEG3 locus promoted somatotroph differentiation and inhibited tumor proliferation in PIT1(+) patients, furthermore, the level of DLK1 played a critical role in the trend of somatotroph or lactotroph differentiation. Anti-DLK1 monoclonal antibody blockade or siMEG3 both indicated that the DLK1/MEG3 significantly promoted the synthesis and secretion of GH/IGF-1 and inhibited cell proliferation. In addition, loss of DLK1 activated the mTOR signaling pathway in high DLK1-expressing and PIT1(+) GH3 cell lines, a mild effect in the low DLK1-expressing and PIT1(+) MMQ cell lines and no effect in the PIT1(-) ATT20 cell line. These findings emphasize that expression at the DLK1/MEG3 locus plays a key role in the differentiation of PitNETs, especially somatotroph adenomas, and provide potential molecular target data for patient stratification and treatment in the future.

SUBMITTER: Chen Y 

PROVIDER: S-EPMC7835058 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Functional characterization of DLK1/MEG3 locus on chromosome 14q32.2 reveals the differentiation of pituitary neuroendocrine tumors.

Chen Yiyuan Y   Gao Hua H   Liu Qian Q   Xie Weiyan W   Li Bin B   Cheng Sen S   Guo Jing J   Fang Qiuyue Q   Zhu Haibo H   Wang Zhuang Z   Wang Jichao J   Li Chuzhong C   Zhang Yazhuo Y  

Aging 20201229 1


Pituitary neuroendocrine tumors (PitNETs) represent the neoplastic proliferation of the anterior pituitary gland. Transcription factors play a key role in the differentiation of PitNETs. However, for a substantial proportion of PitNETs, the etiology is poorly understood. According to the transcription data of 172 patients, we found the imprinting disorders of the 14q32.2 region and DLK1/MEG3 locus associated with the differentiation of PitNETs. DLK1/MEG3 locus promoted somatotroph differentiatio  ...[more]

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2020-11-20 | GSE153089 | GEO