• Title/Summary/Keyword: RNA, small untranslated

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MiRNA Molecular Profiles in Human Medical Conditions: Connecting Lung Cancer and Lung Development Phenomena

  • Aghanoori, Mohamad-Reza;Mirzaei, Behnaz;Tavallaei, Mahmood
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9557-9565
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    • 2014
  • MiRNAs are endogenous, single stranded ~22-nucleotide non-coding RNAs (ncRNAs) which are transcribed by RNA polymerase II and mediate negative post-transcriptional gene regulation through binding to 3'untranslated regions (UTR), possibly open reading frames (ORFs) or 5'UTRs of target mRNAs. MiRNAs are involved in the normal physiology of eukaryotic cells, so dysregulation may be associated with diseases like cancer, and neurodegenerative, heart and other disorders. Among all cancers, lung cancer, with high incidence and mortality worldwide, is classified into two main groups: non-small cell lung cancer and small cell lung cancer. Recent promising studies suggest that gene expression profiles and miRNA signatures could be a useful step in a noninvasive, low-cost and repeatable screening process of lung cancer. Similarly, every stage of lung development during fetal life is associated with specific miRNAs. Since lung development and lung cancer phenomena share the same physiological, biological and molecular processes like cell proliferation, development and shared mRNA or expression regulation pathways, and according to data adopted from various studies, they may have partially shared miRNA signature. Thus, focusing on lung cancer in relation to lung development in miRNA studies might provide clues for lung cancer diagnosis and prognosis.

Effects of different target sites on antisense RNA-mediated regulation of gene expression

  • Park, Hongmarn;Yoon, Yeongseong;Suk, Shinae;Lee, Ji Young;Lee, Younghoon
    • BMB Reports
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    • v.47 no.11
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    • pp.619-624
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    • 2014
  • Antisense RNA is a type of noncoding RNA (ncRNA) that binds to complementary mRNA sequences and induces gene repression by inhibiting translation or degrading mRNA. Recently, several small ncRNAs (sRNAs) have been identified in Escherichia coli that act as antisense RNA mainly via base pairing with mRNA. The base pairing predominantly leads to gene repression, and in some cases, gene activation. In the current study, we examined how the location of target sites affects sRNA-mediated gene regulation. An efficient antisense RNA expression system was developed, and the effects of antisense RNAs on various target sites in a model mRNA were examined. The target sites of antisense RNAs suppressing gene expression were identified, not only in the translation initiation region (TIR) of mRNA, but also at the junction between the coding region and 3' untranslated region. Surprisingly, an antisense RNA recognizing the upstream region of TIR enhanced gene expression through increasing mRNA stability.

Identification and analysis of microRNAs in Candida albicans (Candida albicans의 마이크로RNA 동정과 분석)

  • Cho, Jin-Hyun;Lee, Heon-Jin
    • Journal of Life Science
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    • v.27 no.12
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    • pp.1494-1499
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    • 2017
  • Oral infection due to Candida albicans is a widely recognized and frequent cause of superficial infections of the oral mucosa (oral candidiasis). Although oral candidiasis is not a life-threatening fungemia, it can cause severe problems in individuals under certain conditions. MicroRNAs (miRNAs) are noncoding, small RNA molecules, which regulate the expression of other genes by inhibiting the translation of target mRNAs. The present study was designed to identify miRNAs in C. albicans and determine their possible roles in this organism. miRNA-sized small RNAs (msRNAs) were cloned in C. albicans by deep sequencing, and their secondary structures were analyzed. All the cloned msRNAs satisfied conditions required to qualify them as miRNAs. Bioinformatics analysis revealed that two of the most highly expressed C. albicans msRNAs, Ca-363 and Ca-2019, were located in the 3' untranslated region of the corticosteroid-binding protein 1 (CBP1) gene in a reverse orientation. miRNA mimics were transformed into C. albicans to investigate their RNA-inhibitory functions. RNA oligonucleotide-transformed C. albicans was then observed by fluorescent microscopy. Quantitative PCR analysis showed that these msRNAs did not inhibit CBP1 gene expression 4 hr and 8 hr after ectopic miRNA transformation. These results suggest that msRNAs in C. albicans possess an miRNA-triggered RNA interference gene-silencing function, which is distinct from that exhibited by other eukaryotic systems.

A Review on the Correlation between the Pathology of Alzheimer's Disease and microRNA

  • Kim, Soo-Jung;Cho, Hyun-Jeong
    • Biomedical Science Letters
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    • v.27 no.4
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    • pp.208-215
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    • 2021
  • The purpose of this study was to explain the pathology of Alzheimer's disease (AD) and to investigate the correlation between AD and microRNA. AD is the most common type of dementia, accounting for about 80% of all types of dementia, causing dysfunction in various daily activities such as memory loss, cognitive impairment, and behavioral impairment. The typical pathology of AD is explained by the accumulation of beta-amyloid peptide plaques and neurofibrillary tangles containing hyperphosphorylated tau protein. On the other hand, microRNA is small non-coding RNA 22~23 nucleotides in length that binds to the 3' untranslated region of messenger RNA to inhibit gene expression. Many reports explain that microRNAs found in circulating biofluids are abundant in the central nervous system, are involved in the pathogenic mechanism of AD, and act as important factors for early diagnosis and therapeutic agents of AD. Therefore, this paper aims to clarify the correlation between AD and microRNA. In this review, the basic mechanism of miRNAs is described, and the regulation of miRNAs in the pathological processes of AD are highlighted. Furthermore, we suggest that miRNA-based system in development of therapeutic and diagnostic agents of AD can be a promising tool.

microRNA biomarkers in cystic diseases

  • Woo, Yu Mi;Park, Jong Hoon
    • BMB Reports
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    • v.46 no.7
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    • pp.338-345
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    • 2013
  • microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by targeting the 3'-untranslated region of multiple target genes. Pathogenesis results from defects in several gene sets; therefore, disease progression could be prevented using miRNAs targeting multiple genes. Moreover, recent studies suggest that miRNAs reflect the stage of the specific disease, such as carcinogenesis. Cystic diseases, including polycystic kidney disease, polycystic liver disease, pancreatic cystic disease, and ovarian cystic disease, have common processes of cyst formation in the specific organ. Specifically, epithelial cells initiate abnormal cell proliferation and apoptosis as a result of alterations to key genes. Cysts are caused by fluid accumulation in the lumen. However, the molecular mechanisms underlying cyst formation and progression remain unclear. This review aims to introduce the key miRNAs related to cyst formation, and we suggest that miRNAs could be useful biomarkers and potential therapeutic targets in several cystic diseases.

The Role of MicroRNAs in Regulatory T Cells and in the Immune Response

  • Ha, Tai-You
    • IMMUNE NETWORK
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    • v.11 no.1
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    • pp.11-41
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    • 2011
  • The discovery of microRNA (miRNA) is one of the major scientific breakthroughs in recent years and has revolutionized current cell biology and medical science. miRNAs are small (19~25nt) noncoding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region (3'UTR) of specific messenger RNAs (mRNAs) for degradation of translation repression. Genetic ablation of the miRNA machinery, as well as loss or degradation of certain individual miRNAs, severely compromises immune development and response, and can lead to immune disorders. Several sophisticated regulatory mechanisms are used to maintain immune homeostasis. Regulatory T (Treg) cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. Recent publications have provided compelling evidence that miRNAs are highly expressed in Treg cells, that the expression of Foxp3 is controlled by miRNAs and that a range of miRNAs are involved in the regulation of immunity. A large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as cancer, cardiovascular disease and diabetes, as well as psychiatric and neurological diseases. Although it is still unclear how miRNA controls Treg cell development and function, recent studies certainly indicate that this topic will be the subject of further research. The specific circulating miRNA species may also be useful for the diagnosis, classification, prognosis of diseases and prediction of the therapeutic response. An explosive literature has focussed on the role of miRNA. In this review, I briefly summarize the current studies about the role of miRNAs in Treg cells and in the regulation of the innate and adaptive immune response. I also review the explosive current studies about clinical application of miRNA.

Molecular Characterization of a dsRNA Mycovirus, Fusarium graminearum Virus-DK21, which Is Phylogenetically Related to Hypoviruses but Has a Genome Organization and Gene Expression Strategy Resembling Those of Plant Potex-like Viruses

  • Kwon, Sun-Jung;Lim, Won-Seok;Park, Sang-Ho;Park, Mi-Ri;Kim, Kook-Hyung
    • Molecules and Cells
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    • v.23 no.3
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    • pp.304-315
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    • 2007
  • Fusarium graminearum causes a serious scab disease of small grains in Korea. The nucleotide sequence of the genomic RNA of a double-stranded RNA (dsRNA) virus, Fusarium graminearum virus-DK21 (FgV-DK21), from F. graminearum strain DK21, which is associated with hypovirulence in F. graminearum, was determined and compared to the genome sequences of other mycoviruses, including Cryponectria hypoviruses. The FgV-DK21 dsRNA consists of 6,624 nucleotides, excluding the 3'-terminal poly(A) tail. The viral genome has 53- and 46-nucleotide 5' and 3' untranslated regions (UTRs), respectively, and five putative open reading frames. A phylogenetic analysis of the deduced amino acid sequence of ORF1, which encodes a putative RNA-dependent RNA polymerase, and those of other mycoviruses revealed that this organism forms a distinct virus clade with other hypoviruses, and is more distantly related to other mycoviruses (3.8 to 24.0% identity). However, pairwise sequence comparisons of the nucleotide and deduced amino acid sequences of ORFs 2 through 5 revealed no close relationships to other protein sequences currently available in GenBank. Analyses of RNA accumulation by Northern blot and primer extension indicated that these putative gene products are expressed from at least two different subgenomic RNAs (sgRNAs), in contrast to the cases in other hypoviruses. This study suggests the existence of a new, as yet unassigned, genus of mycoviruses that exhibits a potex-like genome organization and sgRNA accumulation.

MicroRNA-497 Suppresses Proliferation and Induces Apoptosis in Prostate Cancer Cells

  • Wang, Li;Li, Bo;Li, Lei;Wang, Te
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3499-3502
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    • 2013
  • MicroRNAs (miRNAs) are a class of endogenously expressed small, non-coding, single-stranded RNAs that negatively regulate gene expression, mainly by binding to 3'- untranslated regions (3'UTR) of their target messenger RNAs (mRNAs), which cause blocks of translation and/or mRNA cleavage. Recently, miRNAprofiling studies demonstrated the microRNA-497 (miR-497) level to be down-regulated in all prostate carcinomas compared with BPH samples. The purpose of this study was to investigate the potential role of miR-497 in human prostate cancer. Proliferation, cell cycle and apoptosis assays were conducted to explore the potential function of miR-497 in human prostate cancer cells. Results showed that miR-497 suppressed cellular growth and initiated G0/G1 phase arrest of LNCaP and PC-3 cells. We also observed that miR-497 increased the percentage of apoptotic cells by increasing caspase-3/7 activity. Taken together, our results demonstrated that miR-497 can inhibit growth and induce apoptosis by caspase-3 activation in prostate cancer cells, which suggest its use as a potential therapeutic target in the future.

Therapeutic implications of microRNAs in pulmonary arterial hypertension

  • Lee, Aram;McLean, Danielle;Choi, Jihea;Kang, Hyesoo;Chang, Woochul;Kim, Jongmin
    • BMB Reports
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    • v.47 no.6
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    • pp.311-317
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    • 2014
  • microRNAs (miRNAs) are a class of small, non-coding RNAs that play critical posttranscriptional regulatory roles typically through targeting of the 3'-untranslated region of messenger RNA (mRNA). Mature miRNAs are known to be involved in global cellular processes, such as differentiation, proliferation, apoptosis, and organogenesis, due to their capacity to target multiple mRNAs. Thus, imbalances in the expression and/or activity of miRNAs are involved in the pathogenesis of numerous diseases, including pulmonary arterial hypertension (PAH). PAH is a progressive disease characterized by vascular remodeling due to excessive proliferation of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs). Recently, studies have evaluated the roles of miRNAs involved in the pathogenesis of PAH in these pulmonary vascular cells. This review provides an overview of recent discoveries on the role of miRNAs in the pathogenesis of PAH and discusses the potential for miRNAs as therapeutic targets and biomarkers of PAH.

Identification of Caenorhabditis elegans MicroRNA Targets Using a Kernel Method

  • Lee, Wha-Jin;Nam, Jin-Wu;Kim, Sung-Kyu;Zhang, Byoung-Tak
    • Genomics & Informatics
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    • v.3 no.1
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    • pp.15-23
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    • 2005
  • Background MicroRNAs (miRNAs) are a class of noncoding RNAs found in various organisms such as plants and mammals. However, most of the mRNAs regulated by miRNAs are unknown. Furthermore, miRNA targets in genomes cannot be identified by standard sequence comparison since their complementarity to the target sequence is imperfect in general. In this paper, we propose a kernel-based method for the efficient prediction of miRNA targets. To help in distinguishing the false positives from potentially valid targets, we elucidate the features common in experimentally confirmed targets. Results The performance of our prediction method was evaluated by five-fold cross-validation. Our method showed 0.64 and 0.98 in sensitivity and in specificity, respectively. Also, the proposed method reduced the number of false positives by half compared with TargetScan. We investigated the effect of feature sets on the classification of miRNA targets. Finally, we predicted miRNA targets for several miRNAs in the Caenorhabditis elegans (C. elegans) 3' untranslated region (3' UTR) database. Condusions The targets predicted by the suggested method will help in validating more miRNA targets and ultimately in revealing the role of small RNAs in the regulation of genomes. Our algorithm for miRNA target site detection will be able to be improved by additional experimental­knowledge. Also, the increase of the number of confirmed targets is expected to reveal general structural features that can be used to improve their detection.