Loss of copy of MIR1-2 increases CDK4 expression in ileal neuroendocrine tumors
Open Access
- 20 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogenesis
- Vol. 9 (3), 1-9
- https://doi.org/10.1038/s41389-020-0221-4
Abstract
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.Keywords
Funding Information
- Raymond and Beverly Sackler Foundation (n/a)
This publication has 54 references indexed in Scilit:
- The genomic landscape of small intestine neuroendocrine tumorsJCI Insight, 2013
- DAXX / ATRX , MEN1 , and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine TumorsScience, 2011
- Recapitulation of Pancreatic Neuroendocrine Tumors in Human Multiple Endocrine Neoplasia Type I Syndrome via Pdx1-Directed Inactivation of Men1Cancer Research, 2009
- One Hundred Years After “Carcinoid”: Epidemiology of and Prognostic Factors for Neuroendocrine Tumors in 35,825 Cases in the United StatesJournal of Clinical Oncology, 2008
- Assessing Tumor Progression Factors by Somatic Gene Transfer into a Mouse Model: Bcl-xL Promotes Islet Tumor Cell InvasionPLoS Biology, 2007
- Chromosome 18 deletions are common events in classical midgut carcinoid tumorsInternational Journal of Cancer, 2001
- A Transplantable Human Carcinoid as Model for Somatostatin Receptor-Mediated and Amine Transporter-Mediated Radionuclide UptakeThe American Journal of Pathology, 2001
- The retinoblastoma protein and cell cycle controlCell, 1995
- Mutations in the RET proto-oncogene are associated with MEN 2A and FMTCHuman Molecular Genetics, 1993
- Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2ANature, 1993