Exosomes and the kidney: Blaming the messenger

Exosomes are membrane‐bound vesicles of endosomal origin, present in a wide range of biological fluids, including blood and urine. They range between 30 and 100 nm in diameter, and consist of a limiting lipid bilayer, transmembrane proteins and a hydrophilic core containing proteins, mRNAs and microRNAs (miRNA). Exosomes can act as extracellular vehicles by which cells communicate, through the delivery of their functional cargo to recipient cells, with many important biological, physiological and pathological implications. The exosome release pathway contributes towards protein secretion, antigen presentation, pathogen transfer and cancer progression. Exosomes and exosome‐mediated signalling have been implicated in disease processes such as atherosclerosis, calcification and kidney diseases. Circulating levels of exosomes and extracellular vesicles can be influenced by the progression of renal disease. Advances in methods for purification and analysis of exosomes are leading to potential diagnostic and therapeutic avenues for kidney diseases. This review will focus on biophysical properties and biogenesis of exosomes, their pathophysiological roles and their potential as biomarkers and therapeutics in kidney diseases.     

MicroRNA155 in the growth and invasion of salivary adenoid cystic carcinoma

J Oral Pathol Med (2013) 42 : 140–147 Background: The carcinogenesis mechanism of adenoid cystic carcinoma (ACC) of the salivary gland is poorly understood. MicroRNA155 (miRNA155) has been involved in the carcinogenesis of many malignant tumors. The present study aims to examine the role of miRNA155 in tumor growth and invasion of ACC. Methods: MiRNA155 expression was determined in ACC specimens along with normal salivary glands by quantitative PCR. Using ACC‐2 cells as a model for ACC, cell proliferation was examined by MTT assay after knocking down miRNA155 expression, and cell cycle analysis was performed. Invasive capacity of ACC‐2 cells was examined by a Transwell culture assay. The effect of miRNA155 on tumor growth was also examined in vivo using mouse models. The effect of miRNA155 on epidermal growth factor receptor (EGFR)/NF‐κB was studied by quantitative PCR and electrophoretic mobility shift assay. Results: MiRNA155 was over‐expressed in ACC. Proliferation of ACC‐2 cells was markedly inhibited by knocking down miRNA155, resulting from a blockade of cell cycle in the G1 phase. Inhibition of miRNA155 significantly suppressed the invasive capacity of ACC‐2 cells. In vivo growth of ACC‐2 cell‐derived tumors was significantly slower by inhibition of miRNA155. Inhibition of miRNA155 also resulted in decreased expression of EGFR and RelA (NF‐κB). Conclusion: The results suggest that miRNA155 facilitates cell cycle progression and promotes invasion in ACC and that the EGFR/NF‐κB pathway might participate in mediating the effects of miRNA155. This study has provided insights into the carcinogenic mechanisms of ACC and identified new targets for intervention of salivary ACC.     

Hair miR‐29a levels are decreased in patients with scleroderma

In the present study, we evaluated the possibility that we can utilize hair shaft miR‐29a levels as disease marker of scleroderma. Hair samples were obtained from 20 scleroderma patients, five dermatomyositis patients and 13 controls. microRNAs were purified from hairs as well as skins or sera, and miR‐29a levels were measured with quantitative real‐time polymerase chain reaction. Mean hair miR‐29a levels in scleroderma patients were significantly lower than those in control subjects or dermatomyositis, while expression levels of hair shaft marker keratin 34 were similar among them. There was no strong correlation among the miR‐29a levels in the hair, skin and serum of each patient, suggesting that hair microRNAs can be independent biomarkers. We found scleroderma patients with decreased miR‐29a levels had contracture of the phalanges at a significantly higher prevalence than those without. To confirm the clinical usefulness of hair microRNAs, large‐scale researches are needed in the future.     

Targeting miR-205 in breast cancer

As small non-coding regulatory RNAs, microRNAs are capable of silencing gene expression by translational repression or mRNA degradation. Accumulating evidence indicates that deregulation of microRNAs is often associated with human malignancies and suggests a causal role of microRNAs in neoplasia, presumably because microRNAs can function as oncogenes or tumor suppressors. Among them, miR-205 is significantly underexpressed in breast tumors compared with matched normal breast tissue although miR-205 has been shown to be upregulated in some other type of tumors. Furthermore, breast cancer cell lines, including MCF-7 and MDA-MB-231, express a lower level of miR-205 than the non-malignant MCF-10A cells. Ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage-independent growth as well as cell invasion. These findings establish the tumor suppressive role of miR-205, which is probably through direct targeting of oncogenes such as ErbB3 and Zeb1. Therefore, miR-205 may serve as a unique therapeutic target for breast cancer.     

microRNA-21在肝脏中的作用

microRNAs(miRNAs)是一类新发现的小RNAs,因其能调控细胞活动的每个方面,包括分化、生长、代谢、增殖、凋亡和病毒感染、肿瘤生成,已经成为目前研究的热点.最近已有明确的证据表明,miRNAs在肝脏含量丰富并且参与肝脏生理和病理的各个过程.microRNA-21是目前研究最多的miRNAs之一,参与多种肿瘤的发生和一些病理生理改变,但其在肝脏中的研究比较少.本文就mi-croRNA-21在肝再生、肝细胞代谢、肝脏免疫反应及其在肝癌、丙型肝炎等肝病中的作用作一综述.     

急性心肌梗死演进过程中miRNA的作用

急性心肌梗死(AMI)是导致全球心脑血管疾病死亡的主要原因之一,快速高效诊断AMI对疾病的治疗及预后起重要作用。研究认为,微小RNA(microRNA,miRNA)可能成为诊断AMI的重要分子标志物,为AMI治疗提供方向。文章总结了miRNA作为AMI诊断标志物的可行性、对AMI的影响及相关分子机制。     

Diagnostic potential of extracellular vesicle-associated microRNA-10b and tumor markers for lung adenocarcinoma

MicroRNAs (miRNAs/miRs) in extracellular vesicles (EVs) are potential diagnostic markers. The purpose of the present study was to investigate potential EV miRNA biomarkers for lung adenocarcinoma (LUAD). Potential miRNAs were identified by searching public databases and verified by examining clinical samples. The diagnostic value of EV-associated miR-10b, plasma miR-10b and tumor markers (TMs), including α-fetoprotein (AFP), neuron-specific enolase, carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA211), pro-gastrin-releasing-peptide, carbohydrate antigen (CA)125, CA153, CA199 and CA724, was evaluated via receiver operating characteristic curve analysis. By searching the Gene Expression Omnibus and The Cancer Genome Atlas databases, miR-10b was identified as a potential biomarker. The analysis of clinical samples suggested that EV-associated miR-10b from plasma was significantly differentially expressed between LUAD and control samples. EV-associated miR-10b could function as a diagnostic marker for LUAD, with an AUC of 0.998, which was higher than the AUCs for TMs such as AFP, CEA, CYFRA211, CA125, CA153, CA199, CA724, pro-gastrin-releasing-peptide and neuron-specific enolase. In conclusion, EV-associated miR-10b may be a potential diagnostic biomarker for LUAD that is superior to plasma miR-10b and TMs.