长链非编码RNA相关中药作用机制研究进展

中药是我国医药文化的瑰宝,有数千年的应用历史。然而,中药的作用机制尚未完全阐明,这在一定程度上限制了其临床应用。非编码RNA （nocoding RNA,ncRNA）是一类不能编码蛋白的转录体。几类ncRNA已被证实对疾病的发生和发展具有重要的调控作用,包括微小RNA、长链非编码RNA和环状RNA等。近年来,长链非编码RNA相关中药作用机制已成为研究热点。本文综述该领域研究进展,以期为中医药研究提供新思路。     

Inhibition of microRNA-17-5p reduces the inflammation and lipid accumulation,and up-regulates ATP-binding cassette transporterA1 in atherosclerosis

Atherosclerosis (AS) is a chronic inflammatory disease of the arterial wall. Macrophages are considered to be closely associated with the development and progression of AS. However, the precise mechanism of miR-17-5p in the macrophages under AS remains incompletely clarified. This study investigated the regulatory effect of miR-17-5p on the inflammation and lipid accumulation in mouse macrophages both in vivo and in vitro. It was found that miR-17-5p was highly expressed with lowered ATP-binding cassette transporterA1 (ABCA1) level in the peripheral blood leucocytes (PBLs) of AS patients. Moreover, the level of miR-17-5p was up-regulated in the macrophages of ApoE^?/? mice fed with a high-cholesterol diet. Furthermore, we injected miR-17-5p antagomir into AS mice or transfected miR-17-5p inhibitors into mouse macrophage RAW264.7 cells. Results showed that downregulation of miR-17-5p significantly reduced the production of inflammatory cytokines, inhibited the lipid accumulation and up-regulated ABCA1, and activated peroxisome proliferator-activated receptor (PPAR) γ/Liver X receptor (LXR) α signaling pathway. Additionally, ABCA1 was found to be a target of miR-17-5p by directly binding to 3′-untranslated region (3′-UTR) of its mRNA. Our study indicates a novel regulatory mechanism for miR-17-5p by interacting with ABCA1, which could be a therapy-target for the treatment of AS.     

MicroRNA‐198‐5p inhibits the migration and invasion of non‐small lung cancer cells by targeting fucosyltransferase 8

MicroRNA‐198‐5p (miR‐198‐5p) displays crucial roles in various cancers including non‐small cell lung cancer (NSCLC), but the underlying molecular mechanisms remain unclear. Fucosyltransferase 8 (FUT8) is associated with tumour metastasis and prognosis. In this study, we explored the expression of miR‐198‐5p and FUT8 in NSCLC patients. Results showed that miR‐198‐5p was under‐expressed in NSCLC tissues and was negatively correlated with tumour size, lymph node metastasis and tumour‐node‐metastasis stage, while FUT8 expression was highly upregulated. Next, we altered miR‐198‐5p expression using the mimic or inhibitor in the functional study. Results showed that miR‐198‐5p overexpression could inhibit the migration, invasion and epithelial‐to‐mesenchymal transition (EMT) of NSCLC cells; reversely, suppression of miR‐198‐5p enhanced cell migration, invasion and EMT. In vivo, miR‐198‐5p overexpression inhibited the formation of mouse lung and liver metastasis. Luciferase reporter, real‐time PCR and western blot assays showed that miR‐198‐5p could directly target FUT8 and regulate FUT8 expression. Further, FUT8 overexpression reversed the effect of miR‐198‐5p overexpression on the migration, invasion and EMT of NSCLC cells. Taken together, miR‐198‐5p functions as a tumour suppressor by targeting FUT8 in NSCLC. MiR‐198‐5p may be developed as a new diagnostic biomarker and therapeutic target for lung cancer.     

microRNA在急性胰腺炎患者外周血中表达的意义

目的 通过检测血清microRNA变化,预判急性胰腺炎的病情严重度并探讨影响经皮置管引流(PCD)治疗的因素.方法 回顾性分析2013年10月至2014年3月成都军区总医院收治的120例急性胰腺炎患者的临床资料并采集其外周血,35例急性重度胰腺炎(SAP)、急性中重度胰腺炎(MSAP)为A组,85例急性轻度胰腺炎(MAP)为B组.对所有患者进行APACHE Ⅱ、Reason、BISAP评分,用实时定量PCR法进行定量检测患者血清中miR-146a、miR-10b、miR-21、miR-26a表达水平,比较两组之间的4种microRNA表达差异以及与评分系统间的相关性,并分析影响PCD治疗的因素.计量资料采用t检验,变量间关系采用直线相关分析.单因素和多因素分析采用Logistic回归.结果 (1)APACHEⅡ、RANSON、BISAP评分:A组分别为(8.28±0.61)分、(3.42±0.54)分、(1.71±0.32)分;B组分别为(3.18±0.52)分、(1.43±0.25)分、(0.37±0.06)分,两组比较,差异有统计学意义(t=4.266,7.809,4.113,P＜0.05).(2)血清miR-146a、miR-10b、miR-21、miR-26a表达水平:A组分别为1.41±0.21、2.94±0.49、1.62±0.25、1.21±0.20;B组分别为6.29±0.91、0.52±0.09、2.82±0.33、3.57±0.64.miR-146a、miR-10b在两组间差异有统计学意义(=-2.156,2.110,P＜0.05),而miR-21、miR-26a两组间差异无统计学意义(t=-1.114,-1.571,P ＞0.05).(3)相关性:A组miR-146a、miR-10b与APACHEⅡ、RANSON、BISAP评分有相关性(r=-0.826、0.837,-0.874、0.866,-0.833、0.899,P＜0.05).而miR-21、miR-26a表达水平与APACHE Ⅱ、RANSON、BISAP评分无相关性(r=0.642、0.321,0.701、0.750,0.716、0.716,P＞0.05).B组miR-146a、miR-10b、miR-21、miR-26a表达水平与APACHE Ⅱ评分无相关性(r=0.067,0.347,0.133,0.111,P＞0.05);与RANSON评分无相关性(r =0.178,0.078,0.092,0.142,P＞0.05);与BISAP评分无相关性(r=0.103,0.260,0.216,0.285,P＞0.05).(4)预测因素分析:单因素Logistic回归分析发现RANSON评分、BISAP评分、miR-10b是影响PCD干预的因素(OR =4.170,5.612,2.500;95％可信区间:1.092 ～ 15.932,1.232 ～21.622,1.190 ～5.254,P＜0.05).多因素Logistic回归分析发现miR-10b是急性胰腺炎PCD干预的独立影响因素(OR=2.374,95％可信区间:1.115 ～5.056,P＜0.05).结论 miR-10b与miR-146a可能成为判断急性重症胰腺炎严重程度的预测指标;miR-10b可能成为急性胰腺炎是否行PCD干预的判定指标.