Department of Genetics, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
Department of Genetics, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana
Am J Physiol Endocrinol Metab. 2014 Jul 1;307(1):E84-92. doi: 10.1152/ajpendo.00542.2013. Epub 2014 May 13.
Menin, the product of the MEN1 gene, functions as a tumor suppressor and was first identified in 1997 due to its causative role in the endocrine tumor disorder multiple endocrine neoplasia, type 1 (MEN1). More recently, menin has been identified as a key player in pancreatic islet biology with the observation of an inverse relationship between menin levels and pancreatic islet proliferation. However, the factors regulating menin and the MEN1 gene in the pancreas are poorly understood. Here, we describe the regulation of menin by miR-24 and demonstrate that miR-24 directly decreases menin levels and impacts downstream cell cycle inhibitors in MIN6 insulinoma cells and in βlox5 immortalized β-cells. This regulation of menin impacts cell viability and proliferation in βlox5 cells. Furthermore, our data show a feedback regulation between miR-24 and menin that is present in the pancreas, suggesting that miR-24 regulates menin levels in the pancreatic islet.
Menin 是 MEN1 基因的产物，作为一种肿瘤抑制因子，于 1997 年因其在多发性内分泌肿瘤 1 型（MEN1）内分泌肿瘤紊乱中的致病作用而首次被鉴定。最近，menin 被确定为胰岛生物学中的关键参与者，观察到 menin 水平与胰岛增殖呈负相关。然而，调节胰腺中 menin 和 MEN1 基因的因素知之甚少。在这里，我们描述了 miR-24 对 menin 的调节，并证明 miR-24 直接降低 menin 水平，并影响 MIN6 胰岛素瘤细胞和 βlox5 永生化 β 细胞中的下游细胞周期抑制剂。这种 menin 的调节影响了 βlox5 细胞的细胞活力和增殖。此外，我们的数据显示 miR-24 和 menin 之间存在反馈调节，这种调节存在于胰腺中，表明 miR-24 调节胰岛中的 menin 水平。
