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

Oncogenesis 2020 Mar 20;9(3):37. Epub 2020 Mar 20.

Raymond and Beverly Sackler Foundation, New Brunswick, NJ, USA.

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.

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Source
http://dx.doi.org/10.1038/s41389-020-0221-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083839PMC
March 2020

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