Blum Arnon, Yehuda Hila, Geron Nissim, Meerson Ari
Department of Medicine, Padeh Poria Medical Center, Tiberias, Israel.
Faculty of Medicine in the Galilee, Bar Ilan University, Safed, Israel.
Isr Med Assoc J. 2017 Oct;19(10):620-624.
Weight loss surgery is the most effective treatment for obesity, and it reduces cardiovascular and cancer risk through poorly understood mechanisms. MicroRNAs (miRNAs) are short RNA molecules that regulate the stability and translation of many mRNAs. We hypothesized that levels of specific circulating miRNAs are altered following surgery and may contribute to lower cancer risk.
To investigate the change of miRNA following surgery.
All patients underwent gastric "sleeve operation". RNA was isolated from sera of 21 patients (14 men, 7 women) before and 3 months after surgery. Sera were combined into two pools, which served for cDNA library construction followed by miSeq sequencing. The levels of candidate miRNAs were validated in the individual samples by QRT-PCR.
Serum miR-122 was significantly up-regulated 3 months post-bariatric surgery in sera of patients, whose endothelial function had greatly improved. In addition, serum miR-122 levels correlated positively with endothelial function as measured by FMD. The changes in miR-122 levels from pre-surgery to 3 months post-surgery also tended to correlate with the respective changes in FMD.
The serum miR-122/miR-451 ratio may serve as a marker for endothelial function in obese patients. miR-122 is the dominant miRNA in the liver and a known tumor suppressor. Our findings suggest a role for circulating miR-122 in the maintenance of vascular endothelial cells (VECs) and in the prevention of cancer. Further studies are required to elucidate the mechanism of its secretion into circulation and its absorption by VECs, as well as its relevant cellular targets.
减肥手术是治疗肥胖症最有效的方法，它通过尚不清楚的机制降低心血管疾病和癌症风险。微小RNA（miRNA）是短RNA分子，可调节许多mRNA的稳定性和翻译。我们推测，特定循环miRNA的水平在手术后会发生改变，可能有助于降低癌症风险。
研究手术后miRNA的变化。
所有患者均接受了胃“袖状切除术”。从21例患者（14例男性，7例女性）手术前和手术后3个月的血清中分离RNA。血清被合并成两个样本库，用于构建cDNA文库，随后进行miSeq测序。通过QRT-PCR在个体样本中验证候选miRNA的水平。
在接受减肥手术3个月后，患者血清中的miR-122显著上调，其内皮功能得到了极大改善。此外，血清miR-122水平与通过血流介导的血管舒张（FMD）测量的内皮功能呈正相关。从手术前到手术后3个月，miR-122水平的变化也倾向于与FMD的相应变化相关。
血清miR-122/miR-451比值可能作为肥胖患者内皮功能的标志物。miR-122是肝脏中占主导地位的miRNA，也是一种已知的肿瘤抑制因子。我们的研究结果表明，循环miR-122在维持血管内皮细胞（VEC）和预防癌症方面发挥作用。需要进一步研究来阐明其分泌到循环中的机制、被VEC吸收的机制及其相关的细胞靶点。
