Hair shaft miRNA‐221 levels as a new tumor marker of malignant melanoma

miRNA‐221 (miR‐221) is known to be abnormally expressed in many human cancers. The serum levels of miR‐221 have been reported as a tumor marker for malignant melanoma (MM). We hypothesized that the hair shaft miR‐221 levels may be increased in patients with MM. We therefore assessed the possibility that hair shaft miR‐221 levels could be a marker for MM. The hair shaft miR‐221 levels were significantly higher in patients with MM than controls. The rates of increased hair shaft miR‐221 levels above the cut‐off value were comparable to those of serum 5‐S‐CD, which is a tumor marker commonly used for MM. Measurements of the hair shaft miR‐221 levels could have potential clinical value in the detection of MM. This is the first report investigating the hair shaft levels of an miRNA in patients with MM. Our investigations offer new insight into the relationship between miR‐221 and MM, and may provide a new, non‐invasive way to screen for melanoma.     

H∞ control of switched linear discrete‐time systems with polytopic uncertainties

In this paper, the problem of designing H_∞ state‐feedback controllers for switched linear discrete‐time systems with polytopic uncertainties is investigated. Two approaches on designing robust and parameter‐dependent H_∞ controllers are proposed and the existence conditions of the desired controllers are derived and formulated in terms of a set of linear matrix inequalities. By solving the corresponding convex optimization problem, the desired controllers are obtained, respectively, and different optimal H_∞ noise‐attenuation level bounds of corresponding closed‐loop systems are given as well. The designed controllers have their own advantages and disadvantages regarding the conservatism and realization complexity. An illustrative example emerging in networked control systems (NCS) and numerical simulations are presented to show the applicability and effectiveness of the obtained theoretic results. Copyright © 2006 John Wiley & Sons, Ltd.     

A case of dysmyelopoietic syndrome with hypotetraploid karyotype

We present a patient with dysmyelopoietic syndrome and with a complex, hypotetraploid karyotype with numerous structural aberrations.     

黄芪-丹参药对通过下调miR-466b-5p改善高血压肾损害

目的：探讨黄芪-丹参药对通过调节微小核糖核酸-466b-5P（miR-466b-5p）改善高血压肾损害的机制。方法：基于微RNA（miRNA）测序寻找自发性高血压大鼠与Wistar-京都鼠（WKY）的差异基因,构建腺相关病毒转染小鼠,24只C57BL/6小鼠,随机选取12只尾静脉注射小鼠腺相关病毒miR-466b-5P（rAAV-miR-466b-5P）构建miR-466b-5p过表达组,余12只作为空白对照组注射腺相关病毒-9（AAV-9）空载体,转染6周后再各随机分为2组,每组6只,A组（黄芪-丹参+miR-466b-5P过表达组）和C组（黄芪-丹参+空白对照组）以黄芪配方颗粒：2.036 g/kg+丹参配方颗粒：0.255 g/kg灌胃;B组（miR-466b-5P过表达组）和D组（空白对照组）以相同体积生理盐水灌胃;灌胃28 d后观察各组小鼠尿β2-微球蛋白（β2-MG）、N-乙酰-β-D-葡萄糖苷酶（NAG）、微量白蛋白（mALB）,血清胱抑素C（Cys-C）、血管紧张素Ⅱ（AngⅡ）、C反应蛋白（CRP）水平和肾脏病理,进行实时荧光定量(RT-qPCR)与蛋白质印迹法(Western Blotting)寻找其靶基因。结果：1）基于前期miRNA测序选定了miR-466b-5p;2）与D组比较,B组小鼠尿β2-MG、NAG、mALB、血清Cys-C、AngⅡ、CRP均显著升高（P<0.01）;与B组比较,A组小鼠血清Cys-C、CRP明显升高（P<0.05）,尿β2-MG、NAG、mALB、血清AngⅡ无明显改变（P>0.05）;3）与D组比较,B组小鼠出现明显肾小球硬化、小管纤维化,A组较B组有明显改善;4）与D组比较,B组小鼠透明质酸酶2（HAS2）明显下调,而经黄芪-丹参干预后有所回调。结论：miR-466b-5p的过表达会导致高血压肾损害的发生,黄芪-丹参药对通过靶向HAS2下调miR-466b-5p改善高血压肾损害。     

MiR-206 inhibits Head and neck squamous cell carcinoma cell progression by targeting HDAC6 via PTEN/AKT/mTOR pathway

As a kind of endogenous noncoding small RNA, microRNA (miRNA) plays important roles of regulation to various physiological functions, while its affections on senescence of human Head and neck squamous cell carcinoma (HNSCC) are still unknown. The objective of this study was to investigate the effect of miR-206 in HNSCC tissues, adjacent normal tissues and cell lines, and explore its biological functions in HNSCC.In our study, the level of miR-206 in HNSCC tissues and adjacent normal tissues was detected via real-time qPCR. The effect of miR-206 on cell proliferation was tested by MTT assay, colony formation and cell cycle assays. In order to explore the effect of miR-206 on HNSCC cell migration and invasion, we performed wound healing assays and transwell assays. Luciferase reporter assays were designed to identify the interaction between 3′UTR of HDAC6 and miR-206. The level of signaling pathway-related proteins was determined by western blot. The expression of miR-206 was found to be observably decreased in HNSCC tissues and cell lines through real time-PCR. Restoration of miR-206 weaked cell proliferation, invasion and migration in HNSCC cells and the cell cycle was arrest in S phase. Further explores have shown that miR-206 could inhibit HNSCC cells proliferation by targeting the HDAC6 via PTEN/AKT/mTOR pathway. Taken together, our results demonstrated that miR-206 plays a critical role in HNSCC progression by targeting HDAC6 via PTEN/AKT/mTOR pathway, which might be a potential target for diagnostic and therapeutic in HNSCC.     

Silencing of MicroRNA-21 confers the sensitivity to tamoxifen and fulvestrant by enhancing autophagic cell death through inhibition of the PI3K-AKT-mTOR pathway in breast cancer cells

Tamoxifen (TAM) and fulvestrant (FUL) represent the major adjuvant therapy to estrogen receptor-alpha positive (ER⁺) breast cancer patients. However, endocrine resistance to TAM and FUL is a great impediment for successful treatment. We hypothesized that miR-21 might alter the sensitivity of breast cancer cells to TAM or FUL by regulating cell autophagy. Using the ER⁺ breast cancer cells, we knockdown miR-21.by transfection with miR-21 inhibitor, then the cells were exposed to TAM or FUL and the percentages of apoptosis and autophagy were determined. Knockdown of miR-21 significantly increased the TAM or FUL-induced apoptosis in ER⁺ breast cancer cells. Further, silencing of miR-21 in MCF-7 cells enhanced cell autophagy at both basal and TAM or FUL-induced level. The increase of autophagy in miR-21-knockdown MCF-7 cells was also indicated by increase of beclin-1, LC3-II and increased GFP-LC3 dots. Importantly, knockdown of miR-21 contributed to autophagic cell death, which is responsible for part of TAM induced cell death in miR-21 inhibitor-transfected cells. Further analysis suggested that miR-21 inhibitor enhance autophagic cell death through inhibition of PI3K-AKT-mTOR pathway. MiR-21 coordinated the function of autophagy and apoptosis by targeting Phosphatase and tensin homolog (PTEN) through inhibition of PI3K-AKT-mTOR pathway. In conclusion, silencing of miR-21 increased the sensitivity of ER⁺ breast cancer cells to TAM or FUL by increasing autophagic cell death. Targeting autophagy-related miRNAs is a potential strategy for overcoming endocrine resistance to TAM and FUL.     

Up-regulated microRNA-155 expression is associated with poor prognosis in cervical cancer patients

BackgroundMicroRNAs (miRNAs) play important roles in tumor development and progression. The purposes of the study was to investigate the role of miR-155 in cervical cancer.MethodsQuantitative real-time RT-PCR (qRT-PCR) was performed to examine miR-155 expression in cervical cancer tissues and adjacent non-cancerous tissues. The association with overall survival of patients was analyzed by Kaplan-Meier survival analysis. Small interfering RNA (siRNA) was used to suppress miR-155 expression in cervical cancer cells. In vitro assays were performed to further explore the biological functions of miR-155 in cervical cancer.ResultsWe found that miR-155 expression was markedly up-regulated in cervical cancer tissues and correlated with FIGO stage, lymph nodes metastasis, vascular invasion and HPV. Patients with high miR-155 expression level had poorer overall survival than those with low miR-155 expression. Furthermore, multivariate Cox regression analysis suggested that increased miR-155 was an independent prognostic indicator for cervical cancer (P = 0.007; HR = 2.320; 95%CI: 1.259–4.276). Moreover, knockdown of miR-155 was demonstrated to inhibit cell proliferation, migration, and invasion in vitro.ConclusionOur study presents that miR-155 is a novel molecule involved in cervical cancer progression, which provide a potential prognostic biomarker and therapeutic target.     

慢性淋巴细胞性白血病患者miR-9-3甲基化异常及其意义

目的本研究旨在探讨microRNA-9-3(miR-9-3)在慢性淋巴细胞性白血病骨髓细胞中的甲基化异常及其意义。方法采用甲基化特异性聚合酶链反应(MSP)技术检测8例正常骨髓组织、78例新确诊的慢性淋巴细胞性白血病患者和7种白血病细胞株甲基化水平。结果正常对照组miR-9-3呈未甲基化状态;7种白血病细胞株中有5种呈未甲基化状态(71.4%);78例慢性淋巴细胞性白血病患者中65例呈miR-9-3甲基化,MSP阳性率为83%。5-氮杂-2'-脱氧胞苷(5-Aza Dc)处理白血病细胞株后I83-E95和WAC3CD5+细胞株miR-9-3呈未甲基化状态。结论慢性淋巴细胞性白血病患者存在miR-9-3表达受抑,可能与其基因甲基化异常有关。而miR-9-3甲基化在激活慢性淋巴细胞性白血病患者NF-κB1信号通路的作用值得进一步研究。     

多囊卵巢综合征患者血清外泌体中miR-184的表达水平及其对卵巢颗粒细胞增殖的影响

目的研究多囊卵巢综合征(PCOS)患者血清外泌体中miR-184的表达水平及其对卵巢细胞颗粒增殖的影响。方法回顾性选取2018年2月至2020年4月期间盘锦辽油宝石花医院收治的60例PCOS患者作为PCOS组,另纳入同期30名健康成年女性作为对照组,提取2组受试者血清外泌体。应用实时荧光定量聚合酶链式反应(qRT-PCR)法检测2组受试者血清外泌体中及人卵巢颗粒细胞KGN和人正常卵巢上皮细胞IOSE80中的miR-184的相对表达。转染miR-184抑制剂的KGN细胞设为miR-184抑制剂组,转染抑制剂对照物的KGN细胞设为对照组,不做任何处理的KGN细胞设为空白组。应用MTT法检测各组KGN细胞的增殖情况,应用平板克隆实验检测各组KGN细胞的克隆形成率。结果PCOS患者血清外泌体中和KGN细胞中的miR-184的相对表达量为4.23±0.49、5.81±0.73,显著高于对照组(1.32±0.21)和IOSE80组细胞(1.19±0.15),差异有统计学意义(P<0.05)。miR-184抑制剂组KGN细胞在24、48、72、96 h的吸光度值分别为0.20±0.05、0.22±0.07、0.26±0.08、0.29±0.07,均显著低于阴性对照组(0.31±0.09、0.52±0.11、0.78±0.12、0.96±0.18)和空白对照组(0.31±0.08、0.53±0.10、0.77±0.14、0.94±0.18),克隆形成率(26.78±5.98)%显著低于阴性对照组[(45.98±4.12)%]和空白对照组[(43.56±4.34)%],差异有统计学意义(P<0.05)。结论PCOS患者血清外泌体和人卵巢颗粒细胞KGN中miR-184呈现高表达,PCOS的发病可能与miR-184促进卵巢颗粒细胞增殖有关。     

脑膜瘤中miR-200b和ZEB1的表达水平变化及其与预后的关系

目的 探讨脑膜瘤组织中miR-200b、ZEB1表达水平变化与脑膜瘤患者预后的关系。方法 选择2013年5月-2014年12月在本院行神经外科手术治疗的脑膜瘤患者42例,采用qRT-PCR法检测各研究对象脑膜瘤组织与瘤旁组织中miR-200b表达水平,采用免疫组织化学染色法检测ZEB1水平,分析miR-200b、ZEB1表达水平与脑膜瘤临床病理特征的相关性,并对出院后的脑膜瘤患者进行随访,分析miR-200b、ZEB1表达水平变化与脑膜瘤患者预后的关系。结果 脑膜瘤组织miR-200b表达水平显著低于瘤旁组织(P<0.05); 脑膜瘤组织ZEB1阳性表达率高于瘤旁组织(P<0.05); miR-200b、ZEB1表达水平与肿瘤分期有关(P<0.05); miR-200b高表达组的5年无瘤生存率显著高于miR-200b低表达组,ZEB1阳性表达组的5年无瘤生存率显著低于ZEB1阴性表达组(P<0.05); miR-200b低表达、ZEB1阳性表达可能是脑膜瘤患者不良预后的独立危险因素。结论 在脑膜瘤组织中miR-200b低表达、ZEB1阳性表达,且与患者无瘤生存期有关,可作为判断脑膜瘤患者预后的潜在标志物。