The role of oncomirs in the pathogenesis and treatment of breast cancer

Breast cancer, the most common cancer among women, is a heterogeneous and complex disease, which detail of its precise progression mechanisms is less understood. So, an improved comprehension of the precise molecular mechanisms leading to disease progression and design of effective targeted therapies are required for patients with breast cancer. MicroRNAs demonstrate an uncovered class of small and endogenous non-coding RNAs and play an important role in the normal biological processes, including cell differentiation, proliferation and apoptosis. Some miRNAs, known as oncomiR, show different expression levels in cancer and are capable to effect on cellular transformation, carcinogenesis and metastasis and are characterized by high expression levels in tumors compared to normal tissues. Therefore, oncomiRs can be considered as prognostic biomarkers and therapeutic targets in different types of cancers. Moreover, the utilization of oncomiRs as therapeutic targets for cancer is promising. Accordingly, there is evidence which implies an important role of various oncogenic microRNAs in immunopathogenesis of breast cancer. In this review we will discuss about the role of various oncomiRs such as miR-21, miR-155, miR-10b, and miR-221/222 in the pathogenesis and treatment of breast cancer.     

A delivery system specifically approaching bone resorption surfaces to facilitate therapeutic modulation of microRNAs in osteoclasts

Dysregulated microRNAs in osteoclasts could cause many skeletal diseases. The therapeutic manipulation of these pathogenic microRNAs necessitates novel, efficient delivery systems to facilitate microRNAs modulators targeting osteoclasts with minimal off-target effects. Bone resorption surfaces characterized by highly crystallized hydroxyapatite are dominantly occupied by osteoclasts. Considering that the eight repeating sequences of aspartate (D-Asp₈) could preferably bind to highly crystallized hydroxyapatite, we developed a targeting system by conjugating D-Asp₈ peptide with liposome for delivering microRNA modulators specifically to bone resorption surfaces and subsequently encapsulated antagomir-148a (a microRNA modulator suppressing the osteoclastogenic miR-148a), i.e. (D-Asp₈)-liposome-antagomir-148a. Our results demonstrated that D-Asp₈ could facilitate the enrichment of antagomir-148a and the subsequent down-regulation of miR-148a in osteoclasts in vivo, resulting in reduced bone resorption and attenuated deterioration of trabecular architecture in osteoporotic mice. Mechanistically, the osteoclast-targeted delivery depended on the interaction between bone resorption surfaces and D-Asp₈. No detectable liver and kidney toxicity was found in mice after single/multiple dose(s) treatment of (D-Asp₈)-liposome-antagomir-148a. These results indicated that (D-Asp₈)-liposome as a promising osteoclast-targeting delivery system could facilitate clinical translation of microRNA modulators in treating those osteoclast-dysfunction-induced skeletal diseases.     

MicroRNA-based regulatory circuit involved in sperm infertility

miRNAs (MicroRNAs), known as noncoding and important endogenous factors regulating the expression protein-coding genes, are vital regulators in each biological process. Thus, this study aims to explore the key role of four microRNAs in regulating the spermatogenesis. To conduct this experiment, 55 infertile and fertile men provided the study with the sperm and testicular tissue samples. To study the spermatozoa in terms of the morphology, Diff-Quick was applied. Then, quantitative real-time polymerase chain reaction (RT-PCR) was conducted on samples. Our data indicated that in contrast to the miR-15b, significant increasing of miR-383 and miR-122 occurred in both severe oligoasthenoteratozoospermia (SOAT) and moderate oligoasthenoteratozoospermia (MOAT) compared to normal sperm group (N). In addition, it was observed that miR-15b and miR-122 increased in patients with nonobstructive azoospermia (NOA) compared with obstructive azoospermia (OA) group. Expression levels of target genes including P53, CASPASE-9 and CYCLIN D1 underwent principle changes according to miRNAs expression level. Our finding indicated that miRNAs had essential role in the regulation of spermatogenesis, and their expression altering was associated with sperm abnormalities. Thus, microRNAs can be introduced as useful biomarkers to determine male infertility reasons to choose the effective treatment.     

miR-7在肾癌中的表达及临床意义研究

目的检测肾细胞癌组织及相应癌旁正常组织中miR-7的表达,分析18达与临床病理特征之间的关系,为进一步研究miR-7在肾癌的发生发展中作用奠定基础。方法收集48例经手术切除的配对肾癌及癌旁组织标本,提取组织中总RNA,经逆转录获得cDNA,采用实时荧光定量PCR（RT-qPCR）方法检测标本中miR-7表达量,并通过统计学软件分析其表达量与患者临床病理特征之间的相关性。结果与相应癌旁组织相比,肾癌组织中miR-7表达量明显升高,其中34例（70.8%）肾癌标本miR-7表达上调,14例（29.2%）表达下调,差异有统计学意义（P〈0.05）。肾细胞癌中miR-7表达上调与患者年龄、性别、肾癌组织类型、TNM分期、AJCC临床分期无相关性（P〉0.05）。结论 miR-7在肾癌组织中明显高表达,提示其可能与肾癌的发生和发展相关,可能成为肾癌早期诊断、治疗乃至预后判断的新的生物标记物。     

MicroRNA and hepatitis C virus- challenges in investigation and translation: a review of the literature

Investigations into the role of microRNA (miRNA) in hepatitis C virus (HCV) infection, disease pathogenesis and host immune and treatment response have potential to produce innovations in diagnosis, prognosis and therapy. However, investigational challenges remain in generating clinically useful and reproducible results. We review the literature with a primary emphasis on methods and technologies used to construct our current understanding of miRNA and HCV disease. A second emphasis is to understand potential clinical research applications and provide clarification of previous study results. Many miRNA have key roles in viral and immunopathogenesis of HCV infection across multiple tissue compartments. Controversy exists among published studies regarding relative measurements, temporal changes and biological significance of specific miRNA and HCV infection. To reconcile diverging data, additional research into optimal sample processing, in vitro models, techniques for microarray differential expression of miRNAs, practices for sample result normalization, and effect of HCV genotype variation on expression are all necessary. Microarray and miRNA isolation techniques should be selected based on ability to generate reproducible results in the sample type of interest. More direct comparisons of efficacy and reliability of various multiplex microarrays and an improved consensus around miRNA normalization and quantitation are necessary so that data can be compared across studies.     

MicroRNA与肝癌的相关研究

肝癌是消化系统的常见恶性肿瘤,早期诊断困难,治疗手段有限,总体预后较差。近年来随着对MicroRNA深入研究,人们逐渐意识到MicroRNA与肝癌的发生、发展、转移等密切相关,并且在肝癌的早期诊断、治疗及预后评估中有着广阔的前景。本文就近年来关于MicroRNA与肝癌的相关研究作一概述。