Plasma Levels of miR-125b-5p and miR-206 in Acute Ischemic Stroke Patients After Recanalization Treatment: A Prospective Observational Study

Introduction: Multiple microRNAs (miRNAs) participate in the response to hypoxic/ischemic and ischemia-reperfusion events. However, the expression of these miRNAs in circulation from patients with acute ischemic stroke (AIS) receiving recanalization treatment has not been examined, and whether they are associated with the severity and outcome of stroke is still unknown. Materials and methods: In this prospective cohort study, plasma levels of miR-125b-5p, miR-15a-3p, miR-15a-5p, and miR-206 were measured at 24 hours after thrombolysis with or without endovascular treatment in 94 patients with AIS, as determined by qRT-PCR. Stroke severity was assessed based on National Institutes of Health Stroke Scale (NIHSS) score and infarct lesion. Intracranial haemorrhage (ICH) was recorded. An unfavorable outcome was defined as a modified Rankin Scale score greater than 2 at day 90 after stroke. Results: miR-125b-5p and miR-206 levels were correlated with NIHSS scores (P = .014 and P = .002) and cerebral infarction volumes (P = .025 and P = .030). miR-125b-5p levels were significantly higher in patients with an unfavorable outcome than in patients with a favorable outcome (P = .002) and showed good diagnostic accuracy in discriminating the presence of an unfavorable outcome (area under the curve .735, 95% confidence interval .623-.829, P < .001). No association was found between different miRNAs and ICH. Conclusions: In AIS patients after thrombolysis with or without endovascular treatment, miR-125b-5p is a novel prognostic biomarker highly associated with an unfavorable outcome. miR-125b-5p and miR-206 levels are associated with stroke severity.     

MicroRNA profiling in serous cavity specimens: Diagnostic challenges and new opportunities

The cytomorphologic evaluation of serous cavity specimens can quickly determine the cause of an effusion as well as the presence or absence of a neoplastic process. Ancillary tests such as immunohistochemistry and fluorescence in situ hybridization are frequently used to help to definitively identify malignant cells, determine a site of origin, and distinguish between malignant and reactive mesothelial proliferations. In recent years, microRNAs (miRNAs) have been increasingly evaluated in cytologic specimens, including those from serous cavities. The examination of miRNA is attractive because of the stability of miRNA in such specimens and data suggesting that miRNA can provide prognostic and therapeutic information in addition to its role in diagnosis. Furthermore, miRNAs exist within extracellular exosomes, and this allows for their analysis in specimens that contain only rare malignant cells, degenerated cells, or obscuring components. This review discusses the technical aspects of specimen processing for miRNA analysis, recent studies of miRNA expression in malignant serous cavity specimens, and the potential importance of miRNA expression analysis for serous cavity specimens in the near future.     

MiR-96-5p inhibition induces cell apoptosis in gastric adenocarcinoma

BACKGROUND Gastric adenocarcinoma(GAC) mortality rates have remained relatively changed over the past 30 years, and it continues to be one of the leading causes of cancerrelated death.AIM To search for novel mi RNAs related to GAC prognosis and further investigate the effect of mi R-96-5 p on MGC-803 cells.METHODS The mi RNA expression profile data of GAC based on The Cancer Genome Atlas were obtained and used to screen differently expressed mi RNAs(DEMs) and DEMs related to GAC prognosis. Then, the expression of DEMs related to GAC prognosis was identified in GAC tumor samples and adjacent normal samples by q RT-PCR. The target gene, ZDHHC5, of mi R-96-5 p was predicted using Target Scan, mi RTar Base, and mi RDB databases and confirmed by luciferase reporter assay. Furthermore, MGC-803 cells were transfected with inhibitor NC,mi R-96-5 p inhibitor, si-ZDHHC5, or mi R-96-5 p inhibitor + si-ZDHHC5, and then cell apoptosis was detected by flow cytometry. The expression of ZDHHC5, Bcl-2, and COX-2 was detected using western blotting.RESULTS A total of 299 DEMs and 35 DEMs related to GAC prognosis were screened based on The Cancer Genome Atlas. Then compared with adjacent normal samples, the levels of mi R-96-5 p, mi R-222-5 p, and mi R-652-5 p were remarkably increased,while mi R-125-5 p, mi R-145-3 p, and mi R-379-3 p levels were reduced in GAC tumor samples(P 0.01), which were consistent with bioinformatics analysis.Furthermore, ZDHHC5 was defined as a direct target gene of mi R-96-5 p. mi R-96-5 p inhibition increased the number of apoptotic cells as well as promoted the expression of ZDHHC5, Bcl-2, and COX-2 in MGC-803 cells(P 0.01). After ZDHHC5 inhibition, the number of apoptotic cells and the expression of ZDHHC5, Bcl-2, and COX-2 were reduced. The addition of an mi R-96-5 p inhibitor partly reversed these effects(P 0.01).CONCLUSION Our findings identified six mi RNAs related to GAC prognosis and suggested that downregulated mi R-96-5 p might induce cell apoptosis via upregulating ZDHHC5 expression in MGC-803 cells.     

食管鳞状细胞癌中miRNAs的研究进展

食管鳞状细胞癌（esophageal squamous cell carcinoma, ESCC）是我国常见食管癌（esophageal cancer, EC）的主要亚型。虽然ESCC从分子遗传学角度已被广泛研究,但其发病分子机制还没有完全阐明。microRNAs（miRNAs）是一类小的内源性非蛋白编码RNAs,在生理、病理过程中发挥着重要作用,包括细胞分化、凋亡、增殖和代谢。miRNAs通过致癌基因、抑癌基因在ESCC的发病机制中扮演着重要角色。近年来研究表明,许多miRNAs在ESCC组织中的表达存在明显的差异,了解miRNAs及其靶基因在ESCC发生发展中的作用,可能为早期检测、诊断、治疗和预后提供策略。     

阴虚火旺型OLP差异表达miRNAs靶基因功能分析

[目的]探索口腔扁平苔藓(Oral Lichen Planus,OLP)的中医证候研究方法,探寻阴虚火旺型OLP的miRNAs表达特征,分析实验获得的阴虚火旺型OLP差异表达miRNAs的靶基因功能。[方法]选取3例阴虚火旺型口腔扁平苔藓患者及3例正常人血液,分离提取miRNA,荧光标记后与miRNA基因芯片杂交,SAM软件筛选阴虚火旺型OLP患者和正常人有表达差异的miRNA,运用Targetscan软件及Kegg和Biocarta数据库分析阴虚火旺型OLP差异表达miRNAs靶基因功能。[结果]获得U108_x、ENSG00000200969、ENSG00000212315、hsa-miR-18a、hsa-miR-99b5个口腔扁平苔藓特异表达miRNA,其中3个下调,2个上调。hsa-miR-18amiRNA相关的有统计学意义的靶基因功能共8个(P≤0.01);hsa-miR-99bmiRNA基因相关的有统计学意义的靶基因功能共2个(P≤0.05)。[结论]基因芯片技术可用于口腔扁平苔藓中医证候研究,hsa-miR-18a上调和hsa-miR-99b下调可能是阴虚火旺型口腔扁平苔藓的标志性miRNA,并且hsa-miR-18amiRNA基因可能通过调控8个靶基因功能进行对阴虚火旺型OLP发生发展的调控,hsa-miR-99bmiRNA基因可能通过调控2个靶基因功能进行对阴虚火旺型OLP发生发展的调控。     

外泌体miRNA在结核病诊断和预后中的作用

结核病(tuberculosis, TB）作为一种严重的传染病,目前对结核病的预防和治疗仍未取得重大突破,诊断也不够理想。由于结核病的早期发现对于控制和预防感染传播极其重要,并且由于目前结核病诊断的挑战,开发新型生物标志物至关重要。外泌体miRNA是长度为18~22个核苷酸的小非编码RNA,在调节基因表达、翻译和细胞间传递信息中起重要作用。它们作为一种有前途的研究工具,为结核病的诊断和治疗提供了新的视角,近年来研究发现,外泌体与结核病的发生发展有密切的联系。结核病患者的血清外泌体中的miRNA代谢水平失调,可能将这些外体失调的miRNA用作新型生物标志物,用于结核病治疗监测以及活动性疾病的诊断。外泌体miRNA在结核病方面的研究已成为当前的热点之一,被认为是最有前途的候选生物标志物。本文就外泌体miRNA在结核病诊断和预后中的作用研究进展进行综述。     

Increased Ras GTPase activity is regulated by miRNAs that can be attenuated by CDF treatment in pancreatic cancer cells

Ras gene is frequently mutated, and also associated with increased Ras expression and its GTPase activity (activity) in pancreatic cancer (PC), which could in part be due to deregulated expression of microRNAs (miRNAs) contributing to tumor aggressiveness. Here we report, for the first time, that Ras expression and its activity were significantly higher in MIAPaCa-2 cells compared to COLO-357 and BxPC-3 cell lines, which was correlated with loss of let-7 family and miR-143 expression in MIAPaCa-2 cells compared to COLO-357 and BxPC-3 cells. Whereas the expression of miR-21, a frequently up-regulated miRNA in solid tumors was up-regulated in MIAPaCa-2 cells and it was correlated with increased Ras expression and its activity. The miRNAs, let-7i and miR-143 was found to target Ras, and forced re-expression of let-7i and miR-143 inhibited Ras activity, cell proliferation and colony formation in vitro. We also found that the treatment of cells in vitro or treatment of MIAPaCa-2 induced tumors in vivo with CDF, a novel synthetic analog of curcumin, led to the re-expression of let-7 and miR-143, and down-regulated miR-21 expression, which was consistent with attenuation of Ras expression and its activity. Moreover, re-expression of let-7iin vivo resulted in decreased tumor growth and Ras activity. These results suggest that the loss of expression of let-7 and miR-143, and increased expression of miR-21 leads to increased expression of Ras and its GTPase activity, which could be attenuated by CDF treatment and, thus CDF could become a novel therapeutic agent for the treatment of PC.