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

Chen, Yiyuan; Gao, Hua; Liu, Qian; Xie, Weiyan; Li, Bin; Cheng, Sen; Guo, Jing; Fang, Qiuyue; Zhu, Haibo; Wang, Zhuang; Wang, Jichao; Li, Chuzhong; Zhang, Yazhou

doi:10.18632/aging.202376

Cited by 7 publications

(5 citation statements)

References 45 publications

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“…Of interest, NEAT1, which belongs to the same genetic locus as MALAT1, was also expressed at intermediate levels in all samples. Similar results were obtained with MEG3, which has already been reported to be one of the most signi cantly upregulated differentially expressed genes in somatotroph adenomas compared with other PitNET subtypes [17].…”

Section: The Lncrnas In Gh-secreting Pitnetssupporting

confidence: 88%

LCM-RNAseq highlights intratumor heterogeneity and a lncRNA signature from archival tissues of GH-secreting PitNETs

Cis,

Nanni,

Gessi

et al. 2024

Preprint

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Purpose This study explores the potential for hidden variations within seemingly uniform regions of growth hormone -secreting pituitary neuroendocrine tumors (GH-PitNETs). We employed archived tissue samples using Laser Capture Microdissection Sequencing (LCM-RNAseq) to probe the molecular landscape of these tumors at a deeper level. Methods A customized protocol was developed to extract, process, and sequence small amounts of RNA from formalin-fixed, paraffin-embedded (FFPE) tissues derived from five patients with GH-secreting PitNETs and long-term follow-up (≥ 10 years). This approach ensured precise isolation of starting material of enough quality for subsequent sequencing. Results The LCM-RNAseq analysis revealed a surprising level of diversity within seemingly homogeneous tumor regions. Interestingly, the 30 most highly expressed genes included the well-known long noncoding RNA (lncRNA) MALAT1. We further validated the levels of MALAT1 and of other tumor-associated lncRNAs using digital droplet PCR. Conclusion This study demonstrates the potential of LCM-RNAseq to unlock hidden molecular diversity within archived pituitary tumor samples. By focusing on specific cell populations, we identified lncRNAs expressed at different levels within the tumors, potentially offering new insights into the complex biology of GH-secreting PitNETs. This evidence prompts further research into the role of lncRNAs in pituitary neuroendocrine tumor aggressiveness and personalized treatment strategies.

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Section: The Lncrnas In Gh-secreting Pitnetssupporting

confidence: 88%

LCM-RNAseq highlights intratumor heterogeneity and a lncRNA signature from archival tissues of GH-secreting PitNETs

Cis,

Nanni,

Gessi

et al. 2024

Preprint

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“…The miRNome is a determinant of pituitary adenoma molecular classification, with at least 4 different molecular profiles of pituitary adenomas identifiable by miRNome analysis ( 99 ). Interestingly a specific cluster of 85 miRNA, known as MEG3, located on chromosome 14q32.2 and associated with somatotroph adenomas ( 116 ), is associated with GH secretion and a higher expression of PIT1 and DLK1. A main driving effect of this miRNA cluster in pituitary adenoma differentiation is supported by functional studies ( 116 ).…”

Section: Pituitary Tumor Classificationmentioning

confidence: 99%

“…Interestingly a specific cluster of 85 miRNA, known as MEG3, located on chromosome 14q32.2 and associated with somatotroph adenomas ( 116 ), is associated with GH secretion and a higher expression of PIT1 and DLK1. A main driving effect of this miRNA cluster in pituitary adenoma differentiation is supported by functional studies ( 116 ).…”

Section: Pituitary Tumor Classificationmentioning

confidence: 99%

Clinical Biology of the Pituitary Adenoma

et al. 2022

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All endocrine glands are susceptible to neoplastic growth, yet the health consequences of these neoplasms differ between endocrine tissues. Pituitary neoplasms are highly prevalent and overwhelmingly benign, exhibiting a spectrum of diverse behaviors and impact on health. To understand the clinical biology of these common yet often innocuous neoplasms, we review pituitary physiology, and adenoma epidemiology, pathophysiology, behavior, and clinical consequences. The anterior pituitary develops in response to a range of complex brain signals integrating with intrinsic ectodermal cell transcriptional events that together determine gland growth, cell type differentiation, and hormonal production, in turn maintaining optimal endocrine health. Pituitary adenomas occur in ten percent of the population; however, the overwhelming majority remain harmless during life. Triggered by somatic or germline mutations, disease-causing adenomas manifest pathogenic mechanisms that disrupt intra-pituitary signaling to promote benign cell proliferation associated with chromosomal instability. Cellular senescence acts as a mechanistic buffer protecting against malignant transformation, an extremely rare event. It is estimated that fewer than one thousandth of all pituitary adenomas cause clinically significant disease. Adenomas variably and adversely affect morbidity and mortality depending on cell type, hormone secretory activity, and growth behavior. For most clinically apparent adenomas, multimodal therapy controlling hormone secretion and adenoma growth lead to improved quality of life and normalized mortality. The clinical biology of pituitary adenomas and particularly their benign nature stands in marked contrast to other tumors of the endocrine system such as thyroid and neuroendocrine tumors.

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“…Human chromosome 14q32.3 exerts critical functions in differentiation of cells and development of tissues. It comprises an imprinted region, in which MEG3 gene is located, encompassing paternally expressed genes (PEGs), namely, DIO3, DLK1 and RTL1, beside maternally expressed genes (MEGs), namely, MEG3,8 and 9, and numerous huge gatherings of microRNAs [48][49][50] .…”

Section: Maternally Expressed Gene 3 (Meg3)mentioning

confidence: 99%

The Role of lncRNAs in Stroke: MEG3 as a Promising Candidate

Ali

Shaker

Sroor

et al. 2023

Azhar International Journal of Pharmaceutical and Medical Scien

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Globally, stroke is considered a major cause of incapacity and death. It results in high economic load to peoples in almost all countries. Numerous mechanisms have been anticipated to contribute to the pathophysiology of ischemic stroke, including epigenetic modification and dysregulation of some noncoding RNAs. In the recent years, there has been a great focus on studying long noncoding RNAs (lncRNAs) which have been recognized as possible biomarkers and therapeutic goals to treat ischemia. It was observed that maternally expressed gene 3 (MEG3)-lncRNA perform many functions and is implicated in the pathophysiology and/ or recovery of many diseases. Beside the high expression levels of MEG3 in brain, the upregulation of MEG3 after ischemic stroke was also observed. The current review sets sights on spotlighting the functions of lncRNAs, especially MEG3 in the pathogenesis of stroke as well as figuring out its genetic variants that are associated with various diseases, including stroke risk.

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

Cited by 7 publications

References 45 publications

LCM-RNAseq highlights intratumor heterogeneity and a lncRNA signature from archival tissues of GH-secreting PitNETs

LCM-RNAseq highlights intratumor heterogeneity and a lncRNA signature from archival tissues of GH-secreting PitNETs

Clinical Biology of the Pituitary Adenoma

The Role of lncRNAs in Stroke: MEG3 as a Promising Candidate

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