颈动脉超声定量参数联合血清miR-128b、miR-146a对急性缺血性脑卒中的诊断价值及对预后的评价意义

本研究选取了112例急性缺血性脑卒中(AIS)患者作为观察组,另选取112例健康体检者作为对照组。用彩色多普勒超声检测所有对象的颈动脉,并对血清miR-128b、miR-146a水平进行测定,结果发现观察组颈内动脉收缩期峰值血流速度(PSV)、miR-146a低于对照组,舒张末期血流速度(EDV)、颈动脉内膜中层厚度(IMT)、miR-128b高于对照组(P0.05)。颈动脉超声定量参数与两种血清生物标志物联合诊断AIS的AUC为0.898,大于任一单一指标;PSV、EDV、IMT、miR-128b、miR-146a与AIS患者预后(mRs评分)显著相关(P0.05)。颈动脉超声定量参数与两种血清生物标志物联合预测AIS患者预后敏感度达71.43%,特异度达90.48%。颈动脉超声定量参数、血清miR-128b、miR-146a在诊断AIS及预测预后方面具有较高应用价值。     

颈动脉超声联合CT和血清miR-124、miR-155对颈动脉狭窄患者继发性脑梗的风险预测价值

本文探讨了颈动脉超声检查联合CT和血清微小RNA-124(miR-124)、微小RNA-155(miR-155)对颈动脉狭窄患者继发性脑梗的风险预测价值。以43例颈动脉狭窄患者为颈动脉狭窄组,正常志愿者43例为正常组,用RT-PCR法检测miR-124、miR-155表达,采用颈动脉超声检查颈动脉狭窄,采用CT检查颈部血管。结果显示,与正常组相比,颈动脉狭窄组miR-124、miR-155表达升高(P<0.05)。与超声、CT检查相比,超声检查联合CT检查颈动脉狭窄准确率、诊断价值较高(P<0.05)。本研究认为,颈动脉超声、CT、miR-124、miR-155对颈动脉狭窄的诊断价值较高,且可用于预测继发性脑梗的风险,预测价值较为理想。     

双源CT双能量参数联合血清miR-126、miR-204检测对肺癌诊断价值及与临床病理特征关联性

回顾性选取肺癌患者86例为肺癌组,同期肺良性结节患者86例为对照组,患者均行双源CT双能量、血清miR-126、miR-204水平检测,发现静脉期标准化碘浓度(NIC)、动脉期NIC、miR-204、miR-126水平在肺癌组中呈异常表达,并与肺癌组病理类型、临床分期、淋巴结转移存在一定相关性,三者联合对肺癌具有一定诊断价值。同时经Kaplan-Meier生存分析可知,肺癌组静脉期NIC、动脉期NIC高水平患者生存率低于低水平患者,而miR-126、miR-204高水平患者生存率高于低水平患者(P<0.05)。早期采用双源CT双能量、血清miR-126、miR-204联合诊断,可为临床诊治、预后评估提供循证指导。     

miR-526b targets 3′ UTR of MMP1 mRNA

Regulation of matrix metalloproteinases (MMPs) is important for many physiological processes involving cancers, inflammation, tissue remodeling and skin aging. Here, we report the novel finding that the expression of MMP1 mRNA is downregulated by the overexpression of miR-526b which is a member of chromosome 19 microRNA cluster (C19MC). Our analysis using reporter constructs containing the 3′ untranslated region (3′ UTR) of MMP1 and its mutant form showed that the region from 377–383 in the 3′ UTR of MMP1 is critical for targeting by miR-526b. In addition, the expression pattern of miR-526b and MMP1 mRNA showed reverse relation between adult dermal and neonatal fibroblasts. We show for the first time that miR-526b, an miRNA belonging to C19MC, can target the 377–383 region of the MMP1 3′ UTR.     

miR-9 and let-7g enhance the sensitivity to ionizing radiation by suppression of NFκB1

The activation of nuclear factor-kappa B1 (NFkB1) in cancer cells may confer resistance to ionizing radiation (IR). To enhance the therapeutic efficiency of IR in lung cancer, we screened for microRNAs (miRNAs) that suppress NFkB1 and observed their effects on radiosensitivity in a human lung cancer cell line. From time series data of miRNA expression in γ-irradiated H1299 human lung cancer cells, we found that the expression of miR-9 was inversely correlated with that of NFκB1. Overexpression of miR-9 down-regulated the level of NFκB1 in H1299 cells, and the surviving fraction of γ-irradiated cells was decreased. Interestingly, let-7g also suppressed the expression of NFκB1, although there was no canonical target site for let-7g in the NFκB1 3' untranslated region. From these results, we conclude that the expression of miR-9 and let-7g could enhance the efficiency of radiotherapy for lung cancer treatment through the inhibition of NFκB1.     

Zinc oxide nanoparticle attenuates chemotherapy resistance by inducing cell stemness progression of colorectal cancer via miR-1321/HIF-2α axis

BackgroundColorectal cancer (CRC) is the most malignant cancer type with high morbidity and mortality worldwide. Developed drug resistance severely affected the prognosis of CRC patients. This work aimed to explore the effects of zinc oxide nanoparticles (ZONs) in chemo-resistant CRC.MethodsWe established Oxaliplatin (Oxa)-resistant CRC cells, and in vitro and in vivo model to evaluate the function effect of ZONs. Cell counting kit-8 (CCK-8), colony formation, and 5-ethynyl-2′-deoxyuridine (EDU) assay were performed to detect CRC cell viability and proliferation. CRC cell apoptosis was checked by flow cytometry. Tumor cell proliferation was checked by immunohistochemistry (IHC). Cell stemness was determined by sphere formation assay. Luciferase reporter gene assay was conducted to assess the binding of miR-1321 and HIF-2α 3′UTR region.ResultsZONs suppressed the viability and proliferation of Oxa-resistant CRC cells both in vitro and in vivo. ZONs suppressed CRC cell stemness and enhanced the sensitivity of CRC cells to chemo-therapy, along with decreased expression of stem cell biomarkers. ZONs elevated level of miR-1321 and reduced level of HIF-2α in CRC cells. MiR-1321 targeted the 3′UTR region of HIF-2α to suppress its expression. ZONs repressed HIF-2α expression by inducing miR-1321 in CRC cells.ConclusionZONs treatment remarkably converted the drug resistance and stemness of CRC cells, via upregulating miR-1321 to repress the expression of HIF-2α. Our findings suggested that ZONs are potential and effective agent for chemo-resistant CRC patients.     

Emodin prevents intima thickness via Wnt4/Dvl-1/β-catenin signaling pathway mediated by miR-126 in balloon-injured carotid artery rats

Neointimal proliferation after vascular injury is a key mechanism of restenosis, a major cause of percutaneous transluminal angioplasty failure and artery bypass occlusion. Emodin, an anthraquinone with multiple physiological activities, has been reported to inhibit proliferation of vascular smooth muscle cells (VSMCs) that might cause intimal arterial thickening. Thus, in this study, we established a rat model of balloon-injured carotid artery and investigated the therapeutic effect of emodin and its underlying mechanism. Intimal thickness was analyzed by hematoxylin and eosin staining. Expression of Wnt4, dvl-1, β-catenin and collagen was determined by immunohistochemistry and/or western blotting. The proliferation of VSMC was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and electron microscopy. MicroRNA levels were quantified by real-time quantitative PCR. Emodin relieved injury-induced artery intimal thickness. Results of western blots and immunohistochemistry showed that emodin suppressed expression of signaling molecules Wnt4/Dvl-1/β-catenin as well as collagen protein in the injured artery. In addition, emodin enhanced expression of an artery injury-related microRNA, miR-126. In vitro, MTT assay showed that emodin suppressed angiotensin II (AngII)-induced proliferation of VSMCs. Emodin reversed AngII-induced activation of Wnt4/Dvl-1/β-catenin signaling by increasing expression of miR-126 that was strongly supported by transfection of mimic or inhibitor for miR-126. Emodin prevents intimal thickening via Wnt4/Dvl-1/β-catenin signaling pathway mediated by miR-126 in balloon-injured carotid artery of rats.     

Miniaturized electrochemical sensors and their point-of-care applications

Most of the current analytical methods depend largely on laboratory-based analytical techniques that require expensive and bullky equipment,potentially incur costly testing,and involve lengthy detection processes.With increasing requirements for point-of-care testing(POCT),more attention has been paid to miniaturized analytical devices.Miniaturized electrochemical(MEC)sensors,including different material-based MEC sensors(such as DNA-,paper-,and screen electrode-based),have been in strong demand in analytical science due to their easy operation,portability,high sensitivity,as well as their short analysis time.They have been applied for the detection of trace amounts of target through measuring changes in electrochemical signal,such as current,voltage,potential,or impedance,due to the oxidation/reduction of chemical/biological molecules with the help of electrodes and electrochemical units.MEC sensors present great potential for the detection of targets including small organic molecules,metal ions,and biomolecules.In recent years,MEC sensors have been broadly applied to POCT in various fields,including health care,food safety,and environmental monitoring,owing to the excellent advantages of electrochemical(EC)technologies.This review summarized the state-of-the-art advancements on various types of MEC sensors and their applications in POCT.Furthermore,the future perspectives,opportunities,and challenges in this field are also discussed.     

A methoxylated quercetin glycoside harnesses HCC tumor progression in a TP53/miR-15/miR-16 dependent manner

Abstract

This study focused on studying the impact of flavonoids isolated from Cleome droserifolia on HCC cell lines and to further unveil their possible impact on TP53 and its downstream tumor suppressor miRNAs. Three flavonol glycosides were isolated from C. droserifolia namely, Isorhamnetin-3-O-β-D-glucoside (1), Quercetin-3`-methoxy-3-O-(4``-acetylrhamnoside)-7-O-α-rhamnoside (2), and Kaempferol-4`-methoxy-3,7-O-dirhamnoside (3). They showed a concentration and time dependent reduction in cellular viability and anchorage-independent growth of HCC cells. Moreover, they exhibited a decrease in the migrating capacity of HepG2 cells in a pattern similar to positive control cells. (2) Showed the most potent effects in halting HCC tumorigenic activity (IC₅₀=36?±?1.70?µM) and a repression of the cellular proliferation rate of HepG2 cells. Restoration of TP53 and its downstream tumor suppressor miRNAs; miR-15a, miR-16, miR-34a by (2) was observed. Moreover, attenuation of (2) mediated actions was shown upon using anti-miR-15a and anti-miR-16. To conclude, this study crystallizes a novel role of C. droserifolia in harnessing HCC progression in-vitro with a possible contribution of TP53/miR-15a/miR-16.     

The effect of miR-7 on behavior and global protein expression in glioma cell lines

Malignant glioma is a common cancer of the nervous system. Despite recent research efforts in cancer therapy, the prognosis of patients with malignant glioma has remained dismal. MicroRNAs are noncoding RNAs that inhibit the expression of their targets in a sequence-specific manner, and a few have been shown to act as oncogenes or tumor suppressors. Here, we aimed at exploring the precise biological role of microRNA-7 (miR-7) and the global protein changes in glioma cell lines transiently transfected with miR-7. Transfection of miR-7 into glioma cell lines causes inhibition of cell migration and invasion and suppression of tumorigenesis. Moreover, ectopic expression of miR-7 inhibits lung metastases of glioma in vivo. Among 65 protein spots with differential expression separated by 2-DE, 37 proteins were successfully identified by MS/MS analysis. Of those, the 25 downregulated proteins, which include 14-3-3ζ, eukaryotic translation initiation factor 5A (EIF5A), and annexin A4, may be downstream targets of miR-7, a finding that could elucidate some aspects of the behavior of glioma cells at the protein level. In conclusion, the absence of miR-7 function could cause downstream molecules to switch on or off, resulting in glioma development, invasion, and metastases. MiR-7-based gene treatment may be a novel anti-invasion therapeutic strategy for malignant glioma.     

Development of a miRNA-controlled dual-sensing system and its application for targeting miR-21 signaling in tumorigenesis

MicroRNAs (miRNAs) are considered to be strong prognostic markers and key therapeutic targets in human diseases, especially cancer. A sensitive monitoring platform for cancer-associated miRNA (oncomiR) action is needed for mechanistic studies, preclinical evaluation, and inhibitor screening. In this study, we developed and systemically applied a sensitive and efficient lentivirus-based system for monitoring oncomiR actions, essentially miR-21. The specificity and sensitivity of “miRDREL” against various oncomiRs were validated by checking for tight correlations between their expression and targeting efficacy. Experiments based on the transfection of synthetic mimics and antagomir-mediated depletion of oncomiRs further confirmed the specificity of the system. Systemic application of miRDRELs to natural oncomiR targets, knockdown of key microprocessors, and physiological triggering of oncomiRs also demonstrated that the system is an effective tool for monitoring cellular oncomiR action. Importantly, molecular modeling-based screening confirmed the action of the miR-21-targeting drug ivermectin and led to the identification of a new effective derivative, GW4064, for inhibiting oncogenic DDX23-miR-21 signaling. Furthermore, proteomic-kinase inhibitor screenings identified a novel oncogenic kinome-DDX23-miR-21 axis and thus expands our understanding of miR-21 targeting therapeutics in tumorigenesis. Taken together, these data indicate that miRDREL and its versatile application have great potential in basic, preclinical studies and drug development pipelines for miRNA-related diseases, especially cancer.Subject terms: Oncogenes, Cell signalling     

miR-370-3p Regulates Adipogenesis through Targeting Mknk1

Excessive fat accumulation can lead to obesity, diabetes, hyperlipidemia, atherosclerosis, and other diseases. MicroRNAs are a class of microRNAs that regulate gene expression and are highly conserved in function among species. microRNAs have been shown to act as regulatory factors to inhibit fat accumulation in the body. We found that miR-370-3p was expressed at lower levels in the fat mass of mice on a high-fat diet than in mice on a normal control diet. Furthermore, our data showed that the overexpression of miR-370-3p significantly suppressed the mRNA expression levels of adipogenic markers. Thus, miR-370-3p overexpression reduced lipid accumulation. Conversely, the inhibition of miR-370-3p suppressed 3T3-L1 preadipocyte proliferation and promoted preadipocyte differentiation. In addition, Mknk1, a target gene of miR-370-3p, plays an opposing role in preadipocyte proliferation and differentiation. Moreover, consistent results from in vitro as well as in vivo experiments suggest that the inhibition of fat accumulation by miR-370-3p may result from the inhibition of saturated fatty acids that promote the accumulation of polyunsaturated fatty acids. In conclusion, these results suggest that miR-370-3p plays an important role in adipogenesis and fatty acid metabolism through the regulation of Mknk1.