MicroRNA in radiotherapy: miRage or miRador?

At least half of all cancer patients will receive radiation therapy. Tumour radioresistance, or the failure to control certain tumours with this treatment, can result in locoregional recurrence; thus there is great interest in understanding the underlying biology and developing strategies to overcome this problem. The expanding investigation of microRNA in cancer suggests that these regulatory factors can influence the DNA damage response, the microenvironment and survival pathways, among other processes, and thereby may affect tumour radioresistance. As microRNA are readily detectable in tumours and biofluids, they hold promise as predictive biomarkers for therapy response and prognosis. This review highlights the current insights on the major ways that microRNA may contribute to tumour radiation response and whether their levels reflect treatment success. We conclude by applying the potential framework of future roles of miR in personalised radiotherapy using prostate cancer clinical management as an example.     

Overlooked aspects concerning development and spread of antimicrobial resistance

miRNAs are short, nonprotein coding RNAs that regulate target gene expression principally by causing translational repression and/or mRNA degradation. miRNAs are involved in most mammalian biological processes and have pivotal roles in controlling the expression of factors involved in basal and stimulus-induced signaling pathways. Considering their central role in the regulation of gene expression, miRNAs represent therapeutic drug targets. Here we describe how miRNAs are involved in the regulation of aspects of innate immunity and inflammation, what happens when this goes awry, such as in the chronic inflammatory lung diseases cystic fibrosis and asthma, and discuss the current state-of-the-art miRNA-targeted therapeutics.     

Short-Term PCB (Aroclor 1254) Toxicity on Few Phosphatases in Mice Brain

The present communication reports the dose and duration dependent toxicity of a PCB, Aroclor 1254, to a few ion dependent ATPases, Acid phosphatase, Alkaline phosphatase and Glucose-6-phosphatase in the whole brain tissue of mice. Two groups of mice were subjected to two sublethal doses (0.1 and 1 mg kgbw⁻¹ day⁻¹) of PCB orally and exposed for 4, 8 or12 days. A separate control group received the corn oil vehicle for the same exposure times. The observed results indicated exposure duration dependent changes in the enzymatic levels in the brain. The results suggest that the alteration in the enzymatic activity was possibly due to imposed oxidative stress generated by Aroclor 1254 on membrane-bound ion-dependent ATPases and other phosphatases in the brain tissue.     

妊娠期糖尿病患者血清miR-149水平与胰岛素抵抗的关系

【摘要】 目的 探讨妊娠期糖尿病（GDM）患者血清miR-149水平与胰岛素抵抗的关系。 方法 选取2017年1月~2018年8月陕西省人民医院收治的63例妊娠期糖尿病患者设为观察组,选择本院同期产检健康妊娠产妇63例设为对照组,用自动糖化血红蛋白检测仪测定糖化血红蛋白（HbA1c）,用生化分析仪检测受试者餐前空腹血糖(FPG),用免疫测定分析仪检测血清空腹胰岛素（FINS）,计算胰岛素抵抗指数（HOMA IR）=FPG×FINS/22.5。采用实时荧光定量PCR（qRT-PCR）法检测所有研究对象血清miR-149表达水平。用Pearson分析miR-149与血糖、胰岛素等指标的相关性。对影响胰岛素抵抗的相关因素进行Logistic回归分析。 结果 与对照组相比,观察组孕妇HOMA-IR、FPG、FINS、HbA1C水平、miR-149水平较高（P＜0.05）;Pearson法分析显示观察组孕妇血清miR-149水平与FPG、FINS、HOMA-IR呈正相关（P＜0.05）,与HbA1C无相关性（P＞0.05）;多因素Logistic回归分析显示血清miR-149水平升高是影响胰岛素抵抗的危险因素。 结论 妊娠期糖尿病患者血清miR-149水平上调,可能与妊娠期糖尿病孕妇胰岛素抵抗有关。     

circFNDC3B通过抑制miR147表达促进恶性黑素瘤迁移与侵袭

【摘要】目的 探究正常表皮黑素细胞和恶性黑素瘤细胞中环状RNA circFNDC3B的表达水平及其对恶性黑素瘤A2058细胞迁移和侵袭的影响。方法 RT-QPCR实验检测恶性黑素瘤A2058和A375细胞和正常表皮黑素HEMaLP细胞中circFNDC3B表达水平;siRNAs敲低恶性黑素瘤A2058细胞中circFNDC3B的表达;转染siNC和sicircFNDC3B的A2058细胞分别为对照组和实验组,应用细胞划痕实验比较细胞迁移距离,应用免疫印迹实验检测Ecadherin和Ncadherin表达,应用RT QPCR进行检则miRNAs表达。结果 与正常表皮黑素细胞HEMaLP相比,circFNDC3B在恶性黑素瘤细胞中的表达上调。沉默A2058细胞中circFNDC3B 表达后,细胞的迁移和侵袭能力均显著降低（P＜0.05）,Ecadherin表达显著增强,Ncadherin表达显著减弱,抑癌性miRNA miR147表达升高。结论 circFNDC3B在恶性黑素瘤细胞中高表达,可通过抑制miR147表达促进上皮间质转化,进而促进细胞迁移及侵袭。     

A protective polymorphism in MMP16, improved blood gas levels,and chronic obstructive pulmonary diseases: Family and two population‐based studies

The aberrant expression of matrix metalloproteinases (MMPs) is known to contribute to the pathogenesis of airway remodeling and alveolar disruption in chronic obstructive pulmonary disease (COPD). In the discovery stage, 11 COPD from five families were subjected to whole‐genome sequencing, and 21 common polymorphisms in MMPs and TIMPs were identified. These polymorphisms were genotyped in two subsequent verification studies. Of these polymorphisms, c.2392G>A (rs2664370T>C) and c.4158C>A (rs2664369T>G) in MMP16 remained significantly different. Functionally, we found that MMP16 expression was significantly increased in peripheral blood monocytes (PBMCs) from COPD and in cigarette smoke extract‐treated 16HBE cells compared with controls. This was also shown by bioinformatics analysis. COPD carrying rs2664370CC showed decreased levels of MMP16 in the plasma and in PBMCs compared with those carrying CT and TT. Treatment with hsa‐miR‐576‐5p mimics led to a greater reduction in luciferase reporter activity in cells transfected with rs2664370CC. Moreover, blood levels of base excess, PCO₂, and PO₂ in COPD with rs2664370CC were significantly lower than those with rs2664370CT+TT. Taken together, these results demonstrate that the rs2664370T>C polymorphism in MMP16 protects against the risk of COPD, likely by favoring interaction with hsa‐miR‐576‐5p, leading to reduced MMP16 expression and improved blood gas levels.