Deep sequencing reveals novel microRNAs and regulation of microRNA expression during cell senescence

In cell senescence, cultured cells cease proliferating and acquire aberrant gene expression patterns. MicroRNAs (miRNAs) modulate gene expression through translational repression or mRNA degradation and have been implicated in senescence. We used deep sequencing to carry out a comprehensive survey of miRNA expression and involvement in cell senescence. Informatic analysis of small RNA sequence datasets from young and senescent IMR90 human fibroblasts identifies many miRNAs that are regulated (either up or down) with cell senescence. Comparison with mRNA expression profiles reveals potential mRNA targets of these senescence-regulated miRNAs. The target mRNAs are enriched for genes involved in biological processes associated with cell senescence. This result greatly extends existing information on the role of miRNAs in cell senescence and is consistent with miRNAs having a causal role in the process.     

The role of upregulated miRNAs and the identification of novel mRNA targets in prostatospheres

TICs are characterized by their ability to self-renew, differentiate and initiate tumor formation. miRNAs are small noncoding RNAs that bind to mRNAs resulting in regulation of gene expression and biological functions. The role of miRNAs and TICs in cancer progression led us to hypothesize that miRNAs may regulate genes involved in TIC maintenance. Using whole genome miRNA and mRNA expression profiling of TICs from primary prostate cancer cells, we identified a set of up-regulated miRNAs and a set of genes down-regulated in PSs. Inhibition of these miRNAs results in a decrease of prostatosphere formation and an increase in target gene expression. This study uses genome-wide miRNA profiling to analyze expression in TICs. We connect aberrant miRNA expression and deregulated gene expression in TICs. These findings can contribute to a better understanding of the molecular mechanisms governing TIC development/maintenance and the role that miRNAs have in the fundamental biology of TICs.     

Big roles of microRNAs in tumorigenesis and tumor development

MicroRNAs (miRNAs) are a class of endogenous non-protein-coding small RNAs that are evolutionarily conserved and widely distributed among species. Their major function is to negatively regulate target gene expression. A single miRNA can regulate multiple target genes, indicating that miRNAs may regulate multiple signaling pathways and participate in a variety of physiological and pathological processes. Currently, approximately 50% of identified human miRNA-coding genes are located at tumor-related fragile chromosome regions. Abnormal miRNA expression and/or mutations have been found in almost all types of malignancies. These abnormally expressed miRNAs play roles similar to tumor suppressor genes or oncogenes by regulating the expression and/or function of tumor-related genes. Therefore, miRNAs, miRNA target genes, and the genes regulating miRNAs form a regulatory network with miRNAs in the hub. This network plays a pivotal role in tumorigenesis and tumor development.     

Role of microRNAs in endothelial inflammation and senescence

The functionality of endothelial cells is fundamental for the homoeostasis of the vascular system. Increasing evidence shows that endothelial inflammation and senescence contribute greatly to multiple vascular diseases including atherosclerosis. However, little is known regarding the complex upstream regulators of gene expression and translation involved in these responses. MicroRNAs (miRNAs) have emerged as a novel class of endogenous, small, non-coding RNAs that negatively regulate over 30% of genes in a cell via degradation or translational inhibition of their target mRNAs. During the past few years, miRNAs have emerged as key regulators for endothelial biology and function. Endothelial inflammation is critically regulated by miRNAs such as miR-126 and miR-10a in vitro and in vivo. Endothelial aging is additionally controlled by miR-217 and miR-34a. In this review, we summarize the role of miRNAs and their target genes in endothelial inflammation and senescence, and discuss their applicability as drug targets.     

MicroRNAs and intestinal pathophysiology

MicroRNAs (miRNAs) represent an abundant class of endogenously expressed small RNAs, which is believed to control the expression of proteins through specific interaction with their mRNAs. MiRNAs are non-coding RNAs of 18 to 24 nucleotides that negatively regulate target mRNAs by binding to their 3'-untranslated regions (UTR). Most eukaryotic cells utilize miRNA to regulate vital functions such as cell differentiation, proliferation or apopotosis. The diversity of miRNAs and of their mRNA targets strongly indicate that they play a key role in the regulation of protein expression. To date, more than 500 different miRNAs have been identified in animals and plants. There are at least 326 miRNAs in the human genome, comprising 1-4% of all expressed human genes, which makes miRNAs one of the largest classes of gene regulators. A single miRNA can bind to and regulate many different mRNA targets and, conversely, several different miRNAs can bind to and cooperatively control a single mRNA target. The correlation between the expression of miRNAs and their effects on tumorigenesis and on the proliferation of cancer cells is beginning to gain experimental evidences. Recent studies showed that abnormal expression of miRNAs represents a common feature of cancer cells and that they can function as tumor suppressor genes or as oncogenes. Therefore, this diversity of action for miRNAs on several target genes could be one of the common mechanisms involved in the deregulation of protein expression observed during intestinal disorders. In this review, the emergent functions of miRNAs in colorectal cancer and their potential role in the intestinal inflammatory process are discussed.     

植物逆境miRNA研究进展

包括生物和非生物在内的多种逆境胁迫是植物正常生长和作物产量提高的重要限制性因素。植物在长期的进化过程中, 通过诱导表达某些抵御或防卫途径的关键基因来实现对胁迫的响应。研究表明, 逆境胁迫不仅会诱导植物蛋白质编码基因的表达, 也会诱导一些非蛋白质编码基因的表达, 这类非蛋白质编码基因的表达产物在植物的生长、发育和应对逆境胁迫等过程中起到重要的调控作用。miRNA(小分子RNA)就是这类非蛋白质编码基因产物中的重要类群, 研究发现, 多种逆境均会诱导miRNA的产生, 其作用是通过引导目的基因mRNA的降解和阻止翻译过程来调控靶基因, 最终通过形态或生理上的变化达到对逆境的适应。文章主要对植物逆境胁迫下miRNA的研究, 特别是逆境胁迫诱导miRNA的产生、靶基因调控以及miRNA在植物适应逆境胁迫过程中的作用进行了综述, 同时, 文章还对在逆境胁迫下植物miRNA的研究方法进行了初步的探讨。     

miRConnect: identifying effector genes of miRNAs and miRNA families in cancer cells

micro(mi)RNAs are small non-coding RNAs that negatively regulate expression of most mRNAs. They are powerful regulators of various differentiation stages, and the expression of genes that either negatively or positively correlate with expressed miRNAs is expected to hold information on the biological state of the cell and, hence, of the function of the expressed miRNAs. We have compared the large amount of available gene array data on the steady state system of the NCI60 cell lines to two different data sets containing information on the expression of 583 individual miRNAs. In addition, we have generated custom data sets containing expression information of 54 miRNA families sharing the same seed match. We have developed a novel strategy for correlating miRNAs with individual genes based on a summed Pearson Correlation Coefficient (sPCC) that mimics an in silico titration experiment. By focusing on the genes that correlate with the expression of miRNAs without necessarily being direct targets of miRNAs, we have clustered miRNAs into different functional groups. This has resulted in the identification of three novel miRNAs that are linked to the epithelial-to-mesenchymal transition (EMT) in addition to the known EMT regulators of the miR-200 miRNA family. In addition, an analysis of gene signatures associated with EMT, c-MYC activity, and ribosomal protein gene expression allowed us to assign different activities to each of the functional clusters of miRNAs. All correlation data are available via a web interface that allows investigators to identify genes whose expression correlates with the expression of single miRNAs or entire miRNA families. miRConnect.org will aid in identifying pathways regulated by miRNAs without requiring specific knowledge of miRNA targets.     

MicroRNAs: key players of taxane resistance and their therapeutic potential in human cancers

The successful long‐term use of taxane for cancer therapy is often prevented by the development of drug resistance in clinic. Thus, exploring the mechanisms involved is a first step towards rational strategies to overcome taxane resistance. Taxane resistance‐related microRNA (miRNAs) are under investigation and miRNAs could induce the taxane resistance of tumour cells by regulating cell cycle distribution, survival and/or apoptosis pathways, drug transports, epithelial–mesenchymal transition and cancer stem cell. This article summarizes current research involving miRNAs as regulators of key target genes for tanxanxe chemoresistance and discusses the complex regulatory networks of miRNAs. Also, the authors will envisage future developments towards the potential use of targeting miRNAs as a novel strategy for improving response of tumour patients to taxane. miRNAs play critical roles in taxane chemoresistance and the miRNA‐based therapies will be helpful for overcoming drug resistance and developing more effective personalized anti‐cancer treatment strategies. Further research studies should be performed to promote therapeutic–clinical use of taxane resistance‐related miRNAs in cancer patients, especially in those patients with taxane‐resistant cancers.