A Comprehensive Review of Dysregulated miRNAs Involved in Cervical Cancer

MicroRNAs(miRNAs) have become the center of interest in oncology. In recent years, various studies have demonstrated that miRNAs regulate gene expression by influencing important regulatory genes and thus are responsible for causing cervical cancer. Cervical cancer being the third most diagnosed cancer among the females worldwide, is the fourth leading cause of cancer related mortality. Prophylactic human papillomavirus (HPV) vaccines and new HPV screening tests, combined with traditional Pap test screening have greatly reduced cervical cancer. Yet, thousands of women continue to be diagnosed with and die of this preventable disease annually. This has necessitated the scientists to ponder over ways of evolving new methods and chalk out novel treatment protocols/strategies. As miRNA deregulation plays a key role in malignant transformation of cervical cancer along with its targets that can be exploited for both prognostic and therapeutic strategies, we have collected and reviewed the role of miRNA in cervical cancer. A systematic search was performed using PubMed for articles that report aberrant expression of miRNA in cervical cancer. The present review provides comprehensive information for 246 differentially expressed miRNAs gathered from 51 published articles that have been implicated in cervical cancer progression. Of these, more than 40 miRNAs have been reported in the literature in several instances signifying their role in the regulation of cancer. We also identified 40 experimentally validated targets, studied the cause of miRNAs dysregulation along with its mechanism and role in different stages of cervical cancer. We also identified and analysed miRNA clusters and their expression pattern in cervical cancer. This review is expected to further enhance our understanding in this field and serve as a valuable reference resource.     

脂肪组织中的miRNAs研究进展

miRNA是近年来发现的一类长约22 nt的内源性非编码RNA,在动物中主要通过抑制靶mRNA翻译,在转录后水平调控基因表达。大量研究表明脂肪组织中的miRNAs参与了脂肪细胞分化、脂代谢等多种生物过程调控,其自身也受到转录因子、脂肪细胞因子和环境因子等调控,这些复杂的相互作用关系构成了脂肪组织中miRNA的调控网络,循环miRNA的发现为这个网络加入了新元素。对肥胖等代谢疾病的研究,应该从这个复杂的动态网络中寻找答案。文中综述了脂肪组织中miRNA的最新研究进展,以期为利用miRNA进行肥胖等相关代谢失调疾病的治疗提供新思路。     

Novel regulation and functional interaction of polycistronic miRNAs

The importance of microRNAs in gene expression and disease is well recognized. However, what is less appreciated is that almost half of miRNA genes are organized in polycistronic clusters and are therefore coexpressed. The mir-11∼998 cluster consists of two miRNAs, miR-11 and miR-998. Here, we describe a novel layer of regulation that links the processing and expression of miR-998 to the presence of the mir-11 gene. We show that the presence of miR-11 in the pri-miRNA is required for processing by Drosha, and deletion of mir-11 prevents the expression of miR-998. Replacing mir-11 with an unrelated miRNA rescued miR-998 expression in vivo and in vitro, as did expressing miR-998 from a shorter, more canonical miRNA scaffold. The embedded regulation of miR-998 is functionally important because unchecked miR-998 expression in the absence of miR-11 resulted in pleiotropic developmental defects. This novel regulation of expression of miRNAs within a cluster is not limited to the mir-11∼998 cluster and, thus, likely reflects the more general cis-regulation of expression of individual miRNAs. Collectively, our results uncover a novel layer of regulation within miRNA clusters that tempers the functions of the individual miRNAs. Unlinking their expression has the potential to change the expression of multiple miRNA targets and shift a biological response.     

New insight into the role of miRNAs in leukemia

Recent studies have shown that microRNAs(miRNAs) play an important role in cell differentiation, growth, and death, including the functional study of miRNAs in tumorigenesis. To date, miRNA expression profiles in many types of cancers have been identified and miRNA expression signatures associated with types and cytogenetics of leukemia have also been reported. Increasing evidence has shown that miRNAs could function as either tumor suppressors or oncogenes in cancers such as leukemia, while other miRNAs might be benefitcial for diagnosis and prognosis, predicted to be newly developed biomarkers. In this review, we summarize the recent progress about miRNAs in leukemia and present a miRNA-mediated network involved in differentiation, proliferation and apoptosis predicted to be the roles of miRNAs in the pathogenesis of leukemia. Supported by National Natural Science Foundation of China (Grant No. 30672254 and 30872784), National High-Tech Research and Development Program of China (Grant No. 2008AA02Z106).     

Interrogation of rabbit miRNAs and their isomiRs

Rabbit (Oryctolagus cuniculus) is the only lagomorph animal of which the genome has been sequenced. Establishing a rabbit miRNA resource will benefit subsequent functional genomic studies in mammals. We have generated small RNA sequence reads with SOLiD and Solexa platforms to identify rabbit miRNAs, where we identified 464 pre-miRNAs and 886 mature miRNAs. The brain and heart miRNA libraries were used for further in-depth analysis of isomiR distributions. There are several intriguing findings. First, several rabbit pre-miRNAs form highly conserved clusters. Second, there is a preference in selecting one strand as mature miRNA, resulting in an arm selection preference. Third, we analyzed the isomiR expression and validated the expression of isomiR types in different rabbit tissues. Moreover, we further performed additional small RNA libraries and defined miRNAs differentially expressed between brain and heart. We conclude also that isomiR distribution profiles could vary between brain and heart tissues.     

微RNA在卵巢上皮性癌发生发展中作用及其临床意义

研究表明,miRNA参与了胚胎发育、损伤修复、糖尿病、心脏病等许多重要生理病理过程,特别是在恶性肿瘤的发生发展中发挥了重要作用,并具有潜在的临床意义。本文比较详细地叙述了有关miRNA的重要基础研究成果,并就miRNA在卵巢癌组织及细胞中的表达、miRNA在卵巢癌发生发展中的作用、miRNA与卵巢癌早期诊断、化疗耐药及预后判断等方面的最新研究成果进行了综述。     

MicroRNAs and their role in viral infection

Recently,a class of about 22 nucleotides (nt)small RNA has been discovered in many eukaryotes,termed microRNAs (miRNAs),which have a variety of functions.Many recent findings have demonstrated that viruses can also encode their own miRNAs.Meanwhile,other findings reveal a relationship between host miRNA and viral infection.These findings suggest a tight relationship between host and viral infection via miRNA pathway.This article introduces the miRNAs encoded by viruses and reviews the advances of the interaction of the mammalian host miRNAs and viral infection.     

MicroRNAs and their role in viral infection

Recently, a class of about 22 nucleotides (nt) small RNA has been discovered in many eukaryotes, termed microRNAs (miRNAs), which have a variety of functions. Many recent findings have demonstrated that viruses can also encode their own miRNAs. Meanwhile, other findings reveal a relationship between host miRNA and viral infection. These findings suggest a tight relationship between host and viral infection via miRNA pathway. This article introduces the miRNAs encoded by viruses and reviews the advances of the interaction of the mammalian host miRNAs and viral infection.     

The comparison of miRNAs that respond to anti-breast cancer drugs and usnic acid for the treatment of breast cancer

This study was designed to compare usnic acid with anti-breast cancer drug molecules (A-BCDM) routinely used in the treatment of breast cancer. The miRNA information of 17 anti-breast cancer drug used in breast cancer treatment was obtained from the Small Molecule-miRNA Network-Based Inferance (SMIR-NBI) tool. We had been determined common and different expressed miRNAs between 17 A-BCDM & usnic acid and were classified according to the common miRNAs to reveal molecular similarity. As a result of the bioinformatic analyzes, 20 common miRNAs were determined between 17 A-BCDM and usnic acid. The common miRNAs were analyzed with bioinformatic tolls for determining pathways and targets. The most common miRNAs for 6 of 17 A-BCDM and usnic acid were determined as miR-374a-5p and miR-26a-5p. We compared the anti-proliferative effect of usnic acid and one of the 17 A-BCDM that tamoxifen on MDA-MB-231 triple negative breast cancer cell with real-time cell analysis system. The real time PCR assay was carried out with miR-26a-5p for evaluate to expression level of MDA-MB-231 breast cancer cell and MCF-12A non-cancerous epithelial breast cell. As a result of study, usnic acid as novel candidate drug molecule showed high similarity ratio with 5-Fluorouracil, Sulindac Sulfide, Curcumin and Cisplatin A-BCDM used in treatment of breast cancer. miR-26a-5p as common response miRNA of usnic acid and tamoxifen was showed a decreased level of expression by validated qRT-PCR assay. The obtained from study, in addition to 17 A-BCDM, usnic acid has also the potential to be used as a candidate molecule in the treatment of breast cancer. Moreover, miR-26a-5p might be used as a biomarker in the treatment of breast cancer but further analysis is required.