Loss of copy of MIR1-2 increases CDK4 expression in ileal neuroendocrine tumors.

Journal

Oncogenesis

ISSN: 2157-9024

Titre abrégé: Oncogenesis

Pays: United States

ID NLM: 101580004

Informations de publication

Date de publication:
20 Mar 2020

Historique:

received: 19 08 2019

accepted: 25 02 2020

revised: 24 02 2020

entrez: 22 3 2020

pubmed: 22 3 2020

medline: 22 3 2020

Statut: epublish

Résumé

Ileal neuroendocrine tumors (I-NETs) are the most common tumors of the small intestine. Although I-NETs are known for a lack of recurrently mutated genes, a majority of tumors do show loss of one copy of chromosome 18. Among the genes on chromosome 18 is MIR1-2, which encodes a microRNA, MIR1-3p, with high complementarity to the mRNA of CDK4. Here we show that transfection of neuroendocrine cell lines with MIR1-3p lowered CDK4 expression and activity, and arrested growth at the G1 stage of the cell cycle. Loss of copy of MIR1-2 in ileal neuroendocrine tumors associated with increased expression of CDK4. Genetic events that attenuated RB activity, including loss of copy of MIR1-2 as well as loss of copy of CDKN1B and CDKN2A, were more frequent in tumors from patients with metastatic I-NETs. These data suggest that inhibitors of CDK4/CDK6 may benefit patients whose I-NETs show loss of copy of MIR1-2, particularly patients with metastatic disease.

Identifiants

DOI: 10.1038/s41389-020-0221-4 PMID: 32198354 PMC: PMC7083839

pubmed: 32198354

doi: 10.1038/s41389-020-0221-4

pii: 10.1038/s41389-020-0221-4

pmc: PMC7083839

doi:

Types de publication

Journal Article

Langues

eng

Pagination

Subventions

Organisme : Raymond and Beverly Sackler Foundation (Raymond & Beverly Sackler Foundation Inc)

ID : n/a

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