Plasma miR-183 predicts recurrence and prognosis in patients with colorectal cancer

Colorectal cancer (CRC) is one of the most common malignancies worldwide. The prognosis for this cancer is poor, and the development of novel biomarkers, particularly non-invasive surrogate biomarkers, is urgently needed. Recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in the blood and can serve as useful biomarkers for various types of cancer. In this study, the miR-183 expression levels were found to be significantly overexpressed in plasma samples from CRC patients compared with controls, and the postoperative plasma miR-183 levels were significantly reduced compared with the preoperative levels. The value of the area under the receiver operating characteristic (ROC) curve obtained for miR-183 was 0.829, which was higher than those for carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). High plasma miR-183 expression was significantly associated with lymph node metastasis, distant metastasis, higher pTNM stage (III-IV), and tumor recurrence. CRC patients with elevated miR-183 expression in plasma displayed shorter disease-free survival (DFS) and lower overall survival (OS). More importantly, plasma miR-183 was independently correlated with tumor recurrence and a lower OS. Collectively, our results suggested that the elevated miR-183 in the plasma could be a promising biomarker for predicting the risk of tumor recurrence and poor survival in CRC patients.     

MiR-101 reverses the hypomethylation of the LMO3 promoter in glioma cells

LIM-only protein 3 (LMO3), a member of the LIM-only protein group, is a new DNA methylation gene that was identified in gliomas via the MeDIP-Chip in our previous study. In this study, we found that LIM-only protein 3 (LMO3) is hypomethylated and overexpressed in glioma cells and tissues. The overexpression of LMO3 was correlated with a poor prognosis in glioma patients, and LMO3 was indirectly inhibited by the tumor suppressor miR-101, which is a potential prognosis marker of gliomas. MiR-101 decreased the expression of LMO3 by reversing the methylation status of the LMO3 promoter and by inhibiting the presence of the methylation-related histones H3K4me2 and H3K27me3 and increasing the presence of H3K9me3 and H4K20me3 on the promoter. It was determined that miR-101 decreases the occupancy of H3K27me3 by inhibiting EZH2, DNMT3A and EED and decreases the H3K9me3 occupancy on the LMO3 promoter via SUV39H1, SUV39H2, G9a and PHF8. Furthermore, miR-101 suppresses the expression of LMO3 by decreasing USF and MZF1.     

NLK,a novel target of miR-199a-3p,functions as a tumor suppressor in colorectal cancer

We previously reported that miR-199a-3p is a newly biomarker for diagnosis and novel prognostic indicator in colorectal cancer. However, the miR-199a-3p regulatory mechanism and its target genes are still unclear. In our present study, we demonstrated miR-199a-3p could directly target 3′-UTR of NLK gene by luciferase reporter assay and western blot analysis. We detected NLK expressions in 92 colorectal cancer cases to evaluate its clinicopathologic characteristics in colorectal cancer. Our results showed that NLK expression was significantly downregulated in cancer tissues than NATs, and NLK low-expression was associated with lymph node metastasis, venous invasion, liver metastasis and the TNM stage (P < 0.05). Moreover, Kaplan–Meier analysis showed that low expression of NLK correlated with a shorter overall survival rates of patients with CRC (P < 0.05). In vitro, we also found that NLK suppressed the biological behaviors of colorectal cancer cells, including the abilities of cell proliferation, clone formation, wound healing, migration and invasion (P < 0.05), while overexpression of NLK increased the apoptotic rate of colorectal cancer cells. All these results suggested that NLK was an identified miR-199a-3p target gene and functioned as a tumor suppressor gene in colorectal cancer. NLK could be a novel direction for developing diagnostic and therapeutic approaches in colorectal cancer.     

miR-92a/DUSP10/JNK signalling axis promotes human pancreatic cancer cells proliferation

Pancreatic cancer is one of the most common types of cancers in the whole world with a poor prognosis. Finding out how the cancer form and develop is the most important way to cure this cancer. miRNAs, 21–22 nucleotides regulatory small non-coding RNAs, have been found to be critical involved in the growth of pancreatic cancer. In this study, we found that miR-92a was up regulated in three kinds of human pancreatic cancer cell lines. There is a correlation between miR-92a and malignant degree of human pancreatic cancer cell lines. Then we found that miR-92a was essential for promoting cell proliferation in human pancreatic cancer. Inhibition of the function of miR-92a repressed the proliferation of pancreatic cancer cells. Further, we found that miR-92a enhanced the activation of JNK signalling pathway by directly targeting the JNK signalling inhibitor DUSP10. DUSP10 is responsible for miR-92a induced JNK signalling and cell proliferation. Altogether, our study showed a miR-92a/DUSP10/JNK signalling pathway that plays an important role in regulating the proliferation of pancreatic cancer cells.     

miR-370 targeted FoxM1 functions as a tumor suppressor in laryngeal squamous cell carcinoma (LSCC)

microRNAs, a family of small non-coding RNAs, involve in the pathogenesis of several types of cancers, including laryngeal squamous cell carcinoma (LSCC). MiR-370 is frequently aberrant expressed in various types of human cancer including LSCC. However, the role for miR-370 in LSCC remains elusive. Here, we demonstrate that miR-370 was down-regulated in human LSCC tissues. Furthermore, there was an inverse relationship between Forkhead Box ml (FoxM1), which was up-regulated and miR-370 expression in LSCC tissues. FoxM1 was subsequently predicted by bioinformatics and verified to be a target of miR-370 by Luciferase reporter assay. Restored expression of miR-370 in Hep2 cells significantly inhibited cell proliferation. In conclusion, our results suggest that miR-370 may function as a tumor suppressor in LSCC through downregulation of FoxM1, suggesting that miR-370 could serve as a novel potential maker for LSCC therapy.     

miR-122-5p调节创伤性脑外伤后小胶质细胞极化减弱炎症反应北大核心CSCD

目的探讨miR-122-5p对创伤性脑外伤后小胶质细胞凋亡、极化和炎症反应的影响。方法建立创伤性脑外伤(traumatic brain injury,TBI)小鼠模型和细胞模型。使用TBI小鼠脑匀浆刺激星型胶质细胞产生外泌体,microRNA微阵列分析外泌体中显著改变的microRNA。实时荧光定量PCR检测TBI小鼠模型和TBI细胞模型中miR-122-5p表达。使用TUNEL凋亡染色、免疫荧光共聚焦、蛋白质印迹研究miR-122-5p抑制剂在TBI神经炎症中对小胶质细胞凋亡、小胶质细胞M1/M2表型转化、NLRP3通路及NFκB磷酸化的作用。结果通过microRNA微阵列分析发现有83个下调miRNA(改变2倍以上,P<0.05),其中miR-122-5p显著下调(P<0.01),miR-122-5p在TBI小鼠及细胞模型中表达显著下降[(1.0±0.00)vs.(0.41±0.15),P<0.001];[(1.0±0.00)vs.(0.34±0.07),P<0.001]。TUNEL凋亡检测、免疫荧光染色结果表明抑制miR-122-5p表达,可以显著减轻LPS诱导的小胶质细胞凋亡[(8.03±1.30)vs.(3.17±0.34),P<0.001],促进小胶质细胞M1向M2表型转化,即M1表型极化减少[(56.96±13.70)vs.(34.70±3.47),P=0.002],M2表型极化增加[(30.46±3.67)vs.(40.74±2.49),P=0.005]。蛋白质印迹结果表明miR-122-5p抑制剂降低NLRP3炎症小体活化[(0.77±0.10)vs.(0.51±0.11),P=0.02],降低NFκB的磷酸化[(0.73±0.08)vs.(0.50±0.07),P=0.003]。结论miR-122-5p在TBI星形胶质细胞分泌的外泌体及小胶质细胞中表达下调,miR-122-5p抑制剂可以通过抑制TBI后NLRP3炎症小体通路的活化及NFκB的磷酸化,促进小胶质细胞M1向M2表型转化,减少小胶质细胞凋亡,从而减轻TBI后小胶质细胞炎症损伤。     

Induction of delayed hypersensitivity to protein antigens in mice without Freund adjuvants

Three ways for inducing tuberculin-type delayed hypersensitivity (DH) in mice to purified protein antigens without Freund adjuvant are described. Four strains of mice compared for susceptibility to sensitization with several antigens ranked SJL > CF-1 > CAF₁ = C57B1. Females were more easily sensitized than males. The first way of sensitizing without Freund adjuvant was simply to inject antigen intradermally in saline, but it could be used only with the potent antigen methylated human serum albumin (HSA). Six-mercaptopurine injections during the first 5 days of sensitization enhanced such sensitization in CF-1 but inhibited it in CAF₁ mice. The second way sensitized with a weaker antigen, chicken conalbumin (CA), and thus is more versatile. It consisted of injecting a saline solution of antigen into a 24-hr strong DH dermal reaction to an unrelated antigen (dextran). The third way was simplest and best: Freund adjuvant was replaced with aqueous Evans blue dye. Thus, distilled water solutions of antigen (CA or chicken ovalbumin) and dye injected subcutaneously induced DH indistinguishable from that induced with the same antigens in Freund adjuvant. Neither antigen in distilled water alone sensitized. The dye also intensified Arthus sensitization. This diazo dye therefore may be a practical, harmless water-soluble substitute for Freund adjuvant for inducing DH or cell-mediated immunity and for intensifying Arthus sensitization.     

Down-regulation of miR-622 in gastric cancer promotes cellular invasion and tumor metastasis by targeting ING1 gene

AIM:To evaluate the biological and clinical characteristics of miR-622 in gastric cancer. METHODS:We analyzed the expression of miR-622 in 57 pair matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time polymerase chain reaction. Functional analysis of miR-622 expression was assessed in vitro in gastric cancer cell lines with miR-622 precursor and inhibitor. The roles of miR-622 in tumorigenesis and tumor metastasis were analyzed using a stable miR-622 expression plasmid in ...     

急性冠脉综合征患者循环miR-208b-3p与心室重构的关系研究

目的 探究急性冠脉综合征患者循环miR-208b-3p表达水平与心室重构的关系。方法 收集140例西安市第九医院心血管内科2015年11月至2016年12月确诊为急性冠脉综合征患者,实时定量PCR（quantification PCR,qPCR）检测样本miR-208b-3p的表达水平,根据miR-208b-3p表达水平高低以每组同样患者数分为四组,分别比较四组住院及出院1年随访超声测量结果,并对测量值变化率做进一步对比分析。结果 住院期间各超声测量组患者例数之间差异无统计学意义（p>0.05）,出院1年各左心室舒张末期内径（left ventricular end-diastolic dimension,LVDd）组和各左心室射血分数（left ventricular ejection fraction,LVEF）组患者例数的差异具有统计学意义（p=0.046;p=0.036）,各左心室短轴缩短率（fraction shortening,FS）组差异无统计学意义（p>0.05）。变化率分析显示各组LVDd变化率分别为（-0.410±0.125、0.024±0.156、0.082±0.152、0.004±0.078）（p=0.326）;各组FS变化率分别为（0.081±0.379、0.074±0.209、0.061±0.258、0.123±0.310）（p=0.896）;各组LVEF变化率分别为（0.082±0.035、0.046±0.035、0.022±0.037、-0.082±0.052）（p=0.034）。对各组LVEF测量值变化率进行两两对比显示高危组分别与低危组及中低危组差异具有统计学意义（p=0.010;p=0.042）。结论 循环miR-208b-3p与远期心室重构相关,并且对LVEF值的影响最大。