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.

回肠神经内分泌肿瘤（I-NET）是小肠最常见的肿瘤。尽管众所周知I-NET缺乏重复突变的基因，但大多数肿瘤的确显示出丢失了18号染色体的一个拷贝。在18号染色体上的基因是MIR1-2，该基因编码一种微小RNA MIR1-3p，具有高表达。与CDK4 mRNA的互补性。在这里，我们显示用MIR1-3p转染神经内分泌细胞系可降低CDK4的表达和活性，并在细胞周期的G1期阻止其生长。回肠神经内分泌肿瘤中MIR1-2的缺失与CDK4表达升高有关。减弱RB活性的遗传事件，包括MIR1-2拷贝丢失以及MIR1-2拷贝丢失CDKN1B和CDKN2A在具有转移性I-NET的患者的肿瘤中更为常见。这些数据表明，CDK4 / CDK6抑制剂可能有益于I-NETs显示MIR1-2拷贝丢失的患者，特别是患有转移性疾病的患者。