Expression profiles of miRNAs in human pancreatic cancer cell lines

Objective： To analyze initially the differences of miRNAs expression profiles in human pancreatic cancer cell lines by microarray technique. Methods： A total of 743 probes were designed according to the known miRNAs sequences of human, mice, and rats. miRNAs microarray was manufactured and its credibility was verified. Total RNAs were extracted and miRNAs were separated from human pancreatic cancer cell lines （SW1990, Capan-2, BxPC-3, Aspc-1, and Pancl） and immortal human pancreatic duct epithelial cell line H6C7. They were labeled with T4 RNA ligase, then were hybridized with microarray. Through array scan and analysis, miRNAs expression profiles in pancreatic cancer were obtained. The results were verified by Northern blotting and RT-PCR. Results： A total of 63 rniRNAs related to pancreatic cancer were found to be differentially expressed in 5 pancreatic cancer cell lines, including 25 down-regulated and 38 up-regulated miRNAs. Expressions of mir-21 and let-7 were also confirmed： Conclusion： The results suggested that miRNAs expression profiles could be found in pancreatic cancer cells.     

miRNAs与肿瘤血管形成

血管形成是机体一种极其重要的生理过程,它不仅涉及组织再生和创伤愈合,还涉及多种病理过程,如肿瘤的生长与侵袭。在1972年,美国学者Folkman首次提出肿瘤的生长取决于血管形成,正是如此,它使得肿瘤发生转移和无限制生长。miRNA是小的非编码RNA,它作为分子开关调控肿瘤的血管形成,研究表明,miRNA在内皮细胞生物学和肿瘤血管形成方面起着重要的作用,本篇综述将阐述miRNA在肿瘤血管形成中的作用及治疗上的进展。     

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。     

miRNAs在2型糖尿病发病中的作用

2型糖尿病是一个严重的、全球性的慢性疾病,遗传和环境等因素的改变可导致2型糖尿病的发生.尽管胰岛素抵抗(insulin resistance,IR)被认为贯穿2型糖尿病发生、发展的全过程,但其形成的主要病理机制还不十分清楚.微小RNA(miRNAs)是一类内源性非蛋白编码的长度约为20～25 nt的小分子RNA,能在转录后水平调节基因的表达.近年来研究发现miRNAs参与生命过程中一系列的重要进程,如个体发育、器官形成、细胞分化、增殖与凋亡等生物学过程.特别是近年发现miRNAs参与2型糖尿病发生发展的调节.     

Let-7 microRNA as a potential therapeutic target with implications for immunotherapy

ABSTRACT

Introduction: MicroRNAs (miRNA) are a class of small non-coding RNA that play a major role in various cellular processes by negatively regulating gene expression. In the past decade, miRNA dysregulation has been reported to be closely linked to inflammatory diseases. The immune response modulates cancer initiation and progression; miRNAs including let-7 family members have been shown to act as key regulators of the immune responses in various diseases and cancers. Notably, the let-7 miRNA has been reported to be closely associated with immunity, specifically with Toll-like receptors that mediate cytokine expression during pathogen infection and with the regulation of various other immune effectors.

Areas covered: In this review, the authors describe the discovery of let-7 as the starting point of the RNA revolution and highlight let-7 as an efficient tool for cancer and immune therapy.

Expert opinion: let-7 miRNA has emerged as a key player in cancer therapy and immune responses and it has potential role as a new immunotherapeutic target. However, while there are challenges regarding miRNA delivery, the exciting emergence of personalized medicine for cancer and immunotherapy could be beneficial for the development of let-7 therapeutics.     

Targeting CSCs within the tumor microenvironment for cancer therapy: a potential role of mesenchymal stem cells

Introduction: Mesenchymal stem cells (MSCs) are one subgroup of adult stem cells and possess a proliferative potential and ability to differentiate into various ceells.

Areas covered: Emerging evidence suggests that MSCs can reprogram toward cancer stem cells (CSCs), due to alterations of intrinsic and extrinsic microenvironments, leading to tumorigenesis. The CSC concept has fundamental clinical implications because of its involvement in cell migration/invasion, metastasis, and treatment resistance. Therefore, targeting CSCs provides a novel therapeutic strategy for cancer treatment. However, the origin of CSCs and its molecular connections are not fully understood. Emerging evidence suggests the existence of an inter-relationship between CSCs and epithelial-to-mesenchymal transition (EMT) phenotypic cells, in the context of inflammation and hypoxia, as well as the potential role of miRNAs.

Expert opinion: We suggest that targeting CSC signatures along with EMT, inflammation, and hypoxia will provide a more effective therapeutic approach for the elimination of CSCs. To that end, curcumin especially its synthetic novel analog CDF have been shown to attenuate CSC characteristics along with the deregulation of multiple pathways and miRNAs, leading to the inhibition of human tumor growth in vivo, suggesting the potential role of CDF as an anti-tumor agent for the prevention/treatment of tumor progression.     

microRNAs在肾透明细胞癌组织中的表达及意义

目的探讨microRNA(miRNA)在肾透明细胞癌组织中的表达及其临床意义。方法用实时荧光定量PCR技术检测20例肾透明细胞癌患者癌组织与癌旁组织中miRNA-20b、-21、-34a、-210、-141、-200c、200b、-514、-532-5p的表达变化。结果与癌旁组织相比,肾透明细胞癌患者癌组织中miRNA-21、-34a、-210呈高表达(P<0.05),miRNA-141、-200c呈低表达(P<0.05),miRNA-20b、-200b、-514、-532-5p则无差异。miRNA-34a随着肾癌病理分级的增高而增高。结论miRNA-21、-34a、-210、mir-141、-200c在肾透明细胞癌患者癌组织中表达存在差异,可能在肾透明细胞癌中起重要作用。     

MicroRNA-301b-3p accelerates the growth of gastric cancer cells by targeting zinc finger and BTB domain containing 4

MicroRNAs (miRNAs) have been found to be aberrantly expressed and exert essential roles in the tumorigenesis and progression of gastric cancer (GC). miR-301b-3p has been recognized as a cancer-related miRNA in lung cancer, bladder cancer and hepatocellular carcinoma. However, the function of miR-301b-3p in GC progression and its underlying mechanism have not been studied yet. In this study, we found that miR-301b-3p expression was up-regulated in GC tissues compared to adjacent noncancerous tissues. Furthermore, the elevated levels of miR-301b-3p were detected in GC cell lines (SGC-7901, AGS, MKN-45 and MGC-803) as compared with GES-1 cells. Interestingly, GC tissues from patients with tumor size ≥ 5 cm and advanced tumor stages showed obvious higher levels of miR-301b-3p compared to matched controls. Functionally, miR-301b-3p knockdown prominently inhibited cell proliferation, and induced cell cycle arrest at G1 phase and apoptosis in MGC-803 cells. Meanwhile, ectopic expression of miR-301b-3p conversely regulated these biological behaviors of MKN-45 cells. Next, we found that miR-301b-3p knockdown increased, whereas miR-301b-3p overexpression reduced the expression of zinc finger and BTB domain containing 4 (ZBTB4) in GC cells. Accordingly, luciferase reporter assay identified ZBTB4 as a direct target of miR-301b-3p. ZBTB4 overexpression markedly restrained the growth of MGC-803 cells. More importantly, ZBTB4 silencing partially reversed miR-301b-3p knockdown-induced tumor suppressive effects on MGC-803 cells. In conclusion, we firstly revealed that miR-301-3p was highly expressed in GC and contributed to tumor progression via attenuating ZBTB4, which might provide a novel molecular-targeted strategy for GC treatment.