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REVIEW ARTICLE
Year : 2016  |  Volume : 7  |  Issue : 2  |  Page : 68-74

MicroRNA therapeutics: Discovering novel targets and developing specific therapy


Division of Clinical Research, University Centre of Excellence in Research, Baba Farid University of Health Science, Faridkot, Punjab, India

Date of Web Publication31-Mar-2016

Correspondence Address:
Parveen Bansal
Division of Clinical Research, University Centre of Excellence in Research, Baba Farid University of Health Science, Faridkot - 151 203, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2229-3485.179431

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   Abstract 


MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression in diverse biological process. They act as intracellular mediators that are necessary for various biological processes. MicroRNAs targeting pathways of human disease provide a new and potential powerful candidate for therapeutic intervention against various pathological conditions. Even though, the information about miRNA biology has significantly enriched but we still do not completely understand the mechanism of miRNA gene regulation. Various groups across the globe and pharmaceutical companies are conducting research and developments to explore miRNA based therapy and build a whole new area of miroRNA therapeutics. Consequently, few miRNAs have entered the preclinical and clinical stage and soon might be available in the market for use in humans.

Keywords: Clinical stage, gene expression, microRNA, therapeutics


How to cite this article:
Christopher AF, Kaur RP, Kaur G, Kaur A, Gupta V, Bansal P. MicroRNA therapeutics: Discovering novel targets and developing specific therapy. Perspect Clin Res 2016;7:68-74

How to cite this URL:
Christopher AF, Kaur RP, Kaur G, Kaur A, Gupta V, Bansal P. MicroRNA therapeutics: Discovering novel targets and developing specific therapy. Perspect Clin Res [serial online] 2016 [cited 2018 Sep 19];7:68-74. Available from: http://www.picronline.org/text.asp?2016/7/2/68/179431




   Introduction Top


MicroRNAs (miRNAs) are small noncoding RNAs that are approximately 20–25 nucleotides in length. They regulate the expression of multiple target genes through sequence-specific hybridization to the 3′ untranslated region (UTR) of messenger RNAs. These microRNAs block the translation or they can cause direct degradation of their target messenger RNAs. miRNAs do not require perfect complementarity for target recognition, so a single miRNA is responsible for the regulation of multiple messenger RNAs. Although miRNAs exert slight effects on each individual messenger RNA target, the combined effect is significant and produces measurable phenotypic results. miRNAs play integral roles in several biological processes, including immune modulation, metabolic control, neuronal development, cell cycle, muscle differentiation, and stem cell differentiation. Most miRNAs are conserved across multiple animal species, indicating the evolutionary importance of these molecules as modulators of critical biological pathways and processes.

It has been seen that expressions of many miRNAs are altered in different diseases. Some miRNAs are overexpressed whereas some are underexpressed in a particular disease giving rise to signature miRNA pattern. With the discovery of miRNAs and its critical role as regulators in various diseases, it is quiet relevant to explore and understand the possibility of using miRNA as therapeutic agents. Recent studies in animals and humans conducted in different laboratories present data that strengthen the candidature of miRNAs to establish the candidature of miRNAs to establish as a novel class of drugs, i.e., miRNA therapeutics.[1],[2] The miRNAs possess a unique characteristic which is very attractive in terms of drug development, i.e.,. they are small, with known sequences and are often conserved among species. Based on antisense technology, very potent oligonucleotide targeted against miRNA known as anti-miR is being developed. An ideal design for an active synthetic miRNA is that it should bind to its respective targeted miRNA with high affinity and specificity.

This review will focus on miRNA and its biogenesis, importance in various diseases, the potential of using miRNAs as a therapeutic modality, and finally an update on the status of clinical trials.


   History Top


In 1993, first miRNA was discovered during a study on gene Lin-4 of Caenorhabditiselegans.[3] It was seen after the isolation of Lin-4 that the gene encodes a protein that binds to 3′ UTR of Lin-14 mRNA and hence prevents translation of Lin-14. In 2000, second small RNA let-7 was discovered; it repressed Lin-4 mRNA to promote a later developmental transition in C.elegans.[4] Subsequently, it was discovered that lin-4 and let-7 were found in Drosophila and human cells, respectively. Most of the RNAs of this class resembled the Lin-4 and let-7 RNAs, however they had no role in regulating the timing of development thereby suggesting that most of miRNAs were involved in other types of regulatory pathways. Following this, the term “miRNA” to refer to this class of small regulatory RNAs came into existence.

MicroRNAs: Tiny master regulators

The miRNAs are known to be expressed in most organisms from plant to vertebrates (including viruses) and are conserved in all organisms. They regulate gene expression by either degrading or making the targeted mRNAs “silence” rendering their translation into proteins. The miRNAs regulate gene expressions, which affect various biological processes such as cell proliferation, differentiation, survival, and motility. The miRNAs do not require perfect complementarity for target recognition, so a single miRNA is able to regulate multiple mRNAs. On average, a given miRNA can regulate several hundred transcripts whose effector molecules function at various sites within cellular pathways and networks. Consequently, miRNAs are able to switch instantly between cellular programs and are therefore often viewed as tiny master regulators of the human genome.

The miRNAs are predicted using different approaches such as experimental method, computational approach, expressed sequence tag, and genomic survey sequence analysis. However, only a few predicted miRNAs have undergone validation experimentally. Computational analysis indicates that the total number of miRNAs could be more that 1% of total translated genes and more than 30% of protein-coding genes may be targeted by miRNAs.

MicroRNA biogenesis

The miRNA genes are expressed in the cell nucleus. About 70% of the human miRNAs are transcribed from introns and/or exons. A brief overview of miRNA biogenesis is shown in [Figure 1].
Figure 1: Schematic overview of microRNA biogenesis

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Association of microRNA with various diseases

miRNAs are becoming increasingly recognized as their expressions are altered in different diseases such as cancer, hepatitis C infection, myocardial infarction, and metabolic disease. Some miRNAs are overexpressed whereas some are underexpressed in a particular disease giving rise to a signature miRNA pattern. In case of tumors, the miRNAs which are overexpressed may be considered as oncogenes and are called “oncomirs.”[5] They are considered to be involved in tumor development by reciprocally inhibiting tumor suppressor genes (genes that control cell differentiation and apoptosis), for example, miR-17–192 is significantly overexpressed in lung cancer and several other lymphomas. On the other hand, expression of some miRNAs (tumor suppressor) is lower in cancerous cells and usually prevents tumor development by negatively inhibiting oncogenes, for example, let-7 is a tumor suppressor miRNA and aberrant expression of let-7 results in oncogenic loss of differentiation.[6] An overview of the association of signature miRNA with some disease condition is given in [Table 1]. The signature miRNAs associated with disease are discussed in the following sections.
Table 1: Differentially expressed microRNAs (signature microRNAs) in various diseases

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MiR-122 in hepatitis C virus

MiR-122 is the most commonly found miRNA in the adult liver and plays a key role in liver biology that includes development, differentiation, homeostasis, and functions. It controls the metabolism, i.e., cholesterol biosynthesis. miR-122 is involved in the replication of hepatitis C virus (HCV). It binds to the viral genome and enhances viral translation and replication. The binding site in the 5′ end of HCV genome provided the evidence of the direct role of miR-122 into HCV replication.[7],[8]

MiR-33a in metabolic disease

miR-33a targets genes involved in cholesterol export such as the adenosine triphosphate-binding cassette (ABC) transporters ABCA1 and ABCG1 and the endolysosomal transport protein Niemann-Pick C1 (Npc1). In agreement with the regulation of ABCA1 by miR-33, modulation of miR-33a levels results in encompassing effects in cholesterol efflux in macrophages thus suggesting that miR-33 may participate in the regulation of high-density lipoprotein (HDL) levels in vivo. Indeed, three independent studies have demonstrated that endogenous inhibition of miR-33 using different strategies leads to a significant increase in hepatic ABCA1 expression and plasma HDL levels, and these findings were later confirmed in the miR-33 knockout mice.[9]

MiR-155 in inflammatory disease

miR-155 is overexpressed in atopic dermatitis and contributes to chronic skin inflammation by increasing the proliferative response of T-helper cells through the downregulation of cytotoxic T-lymphocyte antigen-4.[10] In autoimmune disorders such as rheumatoid arthritis, miR-155 showed higher expression in patients' tissues and synovial fibroblasts.[11] In multiple sclerosis, increased expression of miR-155 has also been measured in peripheral and central nervous system-resident myeloid cells, including circulating blood monocytes and activated microglia. Overexpression of miR-155 leads to chronic inflammatory state in human.

MiR-10b in glioblastoma

The levels of miR-10b are upregulated in human glioblastoma tissues, glioblastoma cell, and stem cell lines as compared to normal human tissues or astrocytes [12] Inhibition of miR-10b inhibits glioblastoma proliferation, reduces cell invasion, and migration in glioblastoma cell and stem cell lines whereas overexpression of miR-10b induced cell migration and invasion.

MiR-33 in atherosclerosis

Plasma HDL levels have a protective role in atherosclerosis. miR-33, an intronic miRNA located within the SREBF2 gene, suppresses the expression of the cholesterol transporter ABC transporter A1 (ABCA1) and lowers HDL levels. Conversely, mechanisms that inhibit miR-33 increase ABCA1 and circulating HDL levels, suggesting that antagonism of miR-33 may be atheroprotective. In a study, mice deficient for the low-density lipoprotein receptor (LDLr–/– mice), with established atherosclerotic plaques treated with anti-miR33 for 4 weeks, showed an increase in circulating HDL levels and enhanced reverse cholesterol transport to the plasma, liver, and feces.[13] Consistent with this, anti-miR33-treated mice showed reductions in plaque size and lipid content, increased markers of plaque stability, and decreased inflammatory gene expression. Notably, in addition to raising ABCA1 levels in the liver, anti-miR33 oligonucleotides directly targeted the plaque macrophages, in which they enhanced ABCA1 expression and cholesterol removal. Thus, raising HDL levels by anti-miR33 oligonucleotide treatment promotes reverse cholesterol transport and atherosclerosis regression.

MiR-21 in hepatocellular carcinoma

Deregulated expressions of several miRNAs were found to correlate with the pathologic and clinical characteristics of hepatocellular carcinoma HCC.[14] The miRNA microarray analysis has revealed that miR-21 was dramatically elevated in HCC tumor cells, with significant reductions of the expressions of several tumor suppressor genes, including PTEN, PDCD4, RECK, and TPM1 (PTEN).[15] MAP2K3 has also been identified as a novel direct target of miR-21. The study of loss-of-function of miR-21 by transduction of miR-21 sponge in HepG2 cells indicated that miR-21 might regulate cell proliferation, apoptosis, and invasiveness partially by targeting MAP2K3.

MicroRNA as therapeutic target and tool

The expression of miRNAs is altered in various diseases and it is now feasible to manipulate miRNA expression by injecting miRNAs similar to the use of antisense mRNAs and RNAi (widely used techniques for investigating gene function and in gene therapy).[16] As the activation of oncogenes could cause cancer, artificial antisense miRNAs could be synthesized and employed to block their targeted oncomirs to prevent the formation of cancer. However, various critical prerequisite data must be available, for example, identification of signature miRNAs, their mechanism of action, applicability by RNAi, delivery of miRNAs, and their active form in vivo. Once this information is available, miRNA will have a bright future and become a novel therapeutic tool. The process of building miRNA therapeutics is similar to drug discovery and development. Following steps are involved in the discovery and development of miRNA therapeutics [Figure 2]:
Figure 2: Process of microRNA discovery and development

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  • Identification of signature miRNA (done by miRNA profiling in disease)
  • Validation of signature miRNA (loss/gain of function studies in vitro and in animal models)
  • Pharmacological analysis (in vivo miRNA delivery studies, pharmacokinetics/pharmacodynamics, (absorption, distribution, metabolism, excretion, and toxicity studies)
  • Clinical trials (studies on the evaluation of efficacy and safety).


Strategies for microRNA manipulation

There are two main strategies to manipulate miRNAs which are dependent on whether the targeted miRNA expression needs to be downregulated or to re-introduce miRNAs function to restore loss of function. The strategies for miRNA manipulation are summarized in [Table 2].
Table 2: Various microRNAs-based therapeutic strategies investigated in cancer

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Antisense inhibition of mature microRNA (inhibiting oncomirs)

The miRNA antagonists are oligonucleotides containing the complementary sequences of endogenous miRNAs. Antisense oligonucleotide (AMO), also called antagomir, is the most commonly used anti-miRNA antisense oligomer.[2] The locked nucleic acid possess stronger affinity to targeted miRNA, more resistant to nucleases, and have lower toxicity. The peptide nucleic acid (PNA) is an artificial synthesized peptide-structured polymer and is similar to DNA and RNA. The PNA binds the targeted nucleotide more tightly than the nucleotide/nucleotide binding, are relatively stable, have low toxicity, and could be administered systematically.[17] The latest new strategy available is miRNA sponge and miRNA masking. The miRNA sponge downregulates the targeted miRNA and possesses multiple complementary sites to the targeted miRNA,[18] whereas miRNA masking have complimentary miRNA binding site in the 3′ UTR of the target mRNA to inhibit competitively and decreases the activity of endogenous miRNA. The various antisense inhibitors employed for downregulating various miRNAs are depicted in [Table 3].
Table 3: Various methods available for the delivery of microRNAs

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Replacement of microRNAs

In diseases such as cancer, expression levels of downregulated miRNAs or altered miRNA could be done using vector, overexpressing the targeted miRNA or by the transfection of double-stranded miRNAs. Therefore, studies have been conducted by introducing artificial double-stranded miRNA (mimic of targeted downregulated miRNA). For example, overexpression of downregulated miR-26a in hepatocellular carcinoma (HCC) in mouse liver resulted in inhibition of cancer proliferation and initiation of apoptosis. Subsequently in another study, the downregulated miR-34a level was increased by delivering artificial miR-34a with NOV340 liposome in an orthotopic model of HCC.[19] This resulted in significant tumor reduction, prolonged survival, and disease protection in animals.

Patent and clinical trial status of microRNA therapeutics

There is a great excitement regarding miRNA use as therapeutic entities. In terms of scientific perspective, miRNA represents a novel and an attractive target which could manipulate the body functions. Consequently, there has been considerable increase in the number of patent applications filed over the decade. The annual number of US and European published patent applications and issued patents related to miRNAs is close to 500. A snapshot of the current development status of miRNA-based therapeutics is summarized in [Table 4].
Table 4: Overview of microRNAs therapeutics development status

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Future perspectives of microRNA therapeutics

The functionality of miRNA in controlling diverse gene expression in cancer and various other important diseases makes miRNA an ideal candidate for therapeutic applications. Recent data demonstrate that the miRNA expression is altered in various human diseases and its selective modulation through antisense inhibition or replacement could significantly affect the prognosis of a disease. With the technological advancement and ease of administration of miRNA through local or parenteral injection routes and its sufficient uptake in the tissue without the need of developing formulation gives miRNA therapeutics an extra edge. We hope that with increasing research and development on miRNA, increase in the filed patents and increased attention and interest of the biotechnology companies in miRNA-based therapeutics would follow suit. This promises the availability of miRNA therapeutics in the market in the coming years for the treatment of various diseases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Bader AG, Brown D, Winkler M. The promise of microRNA replacement therapy. Cancer Res 2010;70:7027-30.  Back to cited text no. 1
    
2.
Czech MP. MicroRNAs as therapeutic targets. N Engl J Med 2006;354:1194-5.  Back to cited text no. 2
    
3.
Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993;75:843-54.  Back to cited text no. 3
    
4.
Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 2000;403:901-6.  Back to cited text no. 4
    
5.
Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature 2005;435:834-8.  Back to cited text no. 5
    
6.
Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, et al. RAS is regulated by the let-7 microRNA family. Cell 2005;120:635-47.  Back to cited text no. 6
    
7.
Jopling CL, Schütz S, Sarnow P. Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell Host Microbe 2008;4:77-85.  Back to cited text no. 7
    
8.
Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 2005;309:1577-81.  Back to cited text no. 8
    
9.
Marquart TJ, Allen RM, Ory DS, Baldán A. miR-33 links SREBP-2 induction to repression of sterol transporters. Proc Natl Acad Sci U S A 2010;107:12228-32.  Back to cited text no. 9
    
10.
Dorsett Y, McBride KM, Jankovic M, Gazumyan A, Thai TH, Robbiani DF, et al. MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation. Immunity 2008;28:630-8.  Back to cited text no. 10
    
11.
Li X, Tian F, Wang F. Rheumatoid arthritis-associated microRNA-155 targets SOCS1 and upregulates TNF-a and IL-1ß in PBMCs. Int J Mol Sci 2013;14:23910-21.  Back to cited text no. 11
    
12.
Guessous F, Alvarado-Velez M, Marcinkiewicz L, Zhang Y, Kim J, Heister S, et al. Oncogenic effects of miR-10b in glioblastoma stem cells. J Neurooncol 2013;112:153-63.  Back to cited text no. 12
    
13.
Rayner KJ, Sheedy FJ, Esau CC, Hussain FN, Temel RE, Parathath S, et al. Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. J Clin Invest 2011;121:2921-31.  Back to cited text no. 13
    
14.
Aravalli RN. Development of MicroRNA Therapeutics for hepatocellular carcinoma. Diagnostics (Basel) 2013;3:170-91.  Back to cited text no. 14
    
15.
Xu J, Wu C, Che X, Wang L, Yu D, Zhang T, et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog 2011;50:136-42.  Back to cited text no. 15
    
16.
Vidal L, Blagden S, Attard G, de Bono J. Making sense of antisense. Eur J Cancer 2005;41:2812-8.  Back to cited text no. 16
    
17.
Fabani MM, Abreu-Goodger C, Williams D, Lyons PA, Torres AG, Smith KG, et al. Efficient inhibition of miR-155 function in vivo by peptide nucleic acids. Nucleic Acids Res 2010;38:4466-75.  Back to cited text no. 17
    
18.
Lee JB, Hong J, Bonner DK, Poon Z, Hammond PT. Self-assembled RNA interference microsponges for efficient siRNA delivery. Nat Mater 2012;11:316-22.  Back to cited text no. 18
    
19.
Bader AG. miR-34 – A microRNA replacement therapy is headed to the clinic. Front Genet 2012;3:120.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]


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Cell Biology International. 2017; 41(9): 1012
[Pubmed] | [DOI]
36 MTDH and MAP3K1 are direct targets of apoptosis-regulating miRNAs in colorectal carcinoma
Sohair M. Salem,Ahmed R. Hamed,Rehab M. Mosaad
Biomedicine & Pharmacotherapy. 2017; 94: 767
[Pubmed] | [DOI]
37 MicroRNA-135a regulates NHE9 to inhibit proliferation and migration of glioblastoma cells
Daniela M. Gomez Zubieta,Mohamed A. Hamood,Rami Beydoun,Ashley E. Pall,Kalyan C. Kondapalli
Cell Communication and Signaling. 2017; 15(1)
[Pubmed] | [DOI]
38 Inflammasome Priming in Sterile Inflammatory Disease
Meghana N. Patel,Richard G. Carroll,Silvia Galván-Peña,Evanna L. Mills,Robin Olden,Martha Triantafilou,Amaya I. Wolf,Clare E. Bryant,Kathy Triantafilou,Seth L. Masters
Trends in Molecular Medicine. 2017; 23(2): 165
[Pubmed] | [DOI]
39 A Circulating microRNA Signature Predicts Age-Based Development of Lymphoma
Afshin Beheshti,Charles Vanderburg,J. Tyson McDonald,Charusheila Ramkumar,Tatenda Kadungure,Hong Zhang,Ronald B. Gartenhaus,Andrew M. Evens,Jianjun Zhao
PLOS ONE. 2017; 12(1): e0170521
[Pubmed] | [DOI]
40 MiR-138-5p targeting LIMK1 suppresses breast cancer cell proliferation and motility
Dengfeng Li,Hongming Song,Tianqi Wu,Dan Xie,Jiashu Hu,Junyong Zhao,Lin Fang
RSC Advances. 2017; 7(82): 52030
[Pubmed] | [DOI]
41 MiR-145 ameliorates neuropathic pain via inhibiting inflammatory responses and mTOR signaling pathway by targeting Akt3 in a rat model
Jinshan Shi,Ke Jiang,Zhaoduan Li
Neuroscience Research. 2017;
[Pubmed] | [DOI]
42 Triangle of AKT2, miRNA, and Tumorigenesis in Different Cancers
Maryam Honardoost,Seyed Mohammad Ali Hosseini Rad
Applied Biochemistry and Biotechnology. 2017;
[Pubmed] | [DOI]
43 High miR-205 expression in normal epithelium is associated with biochemical failure - an argument for epithelial crosstalk in prostate cancer?
Yngve Nordby,Elin Richardsen,Nora Ness,Tom Donnem,Hiten R. H. Patel,Lill-Tove Busund,Roy M. Bremnes,Sigve Andersen
Scientific Reports. 2017; 7(1)
[Pubmed] | [DOI]
44 Role of miRNAs in human disease and inborn errors of metabolism
Ana Rivera-Barahona,Belén Pérez,Eva Richard,Lourdes R. Desviat
Journal of Inherited Metabolic Disease. 2017;
[Pubmed] | [DOI]
45 Inflammation-induced miRNA-155 inhibits self-renewal of neural stem cells via suppression of CCAAT/enhancer binding protein ß (C/EBPß) expression
Kayoko Obora,Yuta Onodera,Toshiyuki Takehara,John Frampton,Joe Hasei,Toshifumi Ozaki,Takeshi Teramura,Kanji Fukuda
Scientific Reports. 2017; 7: 43604
[Pubmed] | [DOI]
46 The Potential of MicroRNAs as Novel Biomarkers for Transplant Rejection
Matthias Hamdorf,Satoru Kawakita,Matthew Everly
Journal of Immunology Research. 2017; 2017: 1
[Pubmed] | [DOI]
47 MicroRNA-467g inhibits new bone regeneration by targeting Ihh/Runx-2 signaling
Jyoti Kureel,Aijaz A John,Manisha Dixit,Divya Singh
The International Journal of Biochemistry & Cell Biology. 2017;
[Pubmed] | [DOI]
48 Shields Up—Systemic Protection Provided by microRNA-21 During Sepsis?*
Cliona Ni Cheallaigh,Frederick J. Sheedy
Critical Care Medicine. 2017; 45(7): 1261
[Pubmed] | [DOI]
49 Colorectal Cancer: From the Genetic Model to Posttranscriptional Regulation by Noncoding RNAs
María Antonia Lizarbe,Jorge Calle-Espinosa,Eva Fernández-Lizarbe,Sara Fernández-Lizarbe,Miguel Ángel Robles,Nieves Olmo,Javier Turnay
BioMed Research International. 2017; 2017: 1
[Pubmed] | [DOI]
50 Advances in the delivery of RNA therapeutics: from concept to clinical reality
James C. Kaczmarek,Piotr S. Kowalski,Daniel G. Anderson
Genome Medicine. 2017; 9(1)
[Pubmed] | [DOI]
51 Potent Anti-seizure Effects of Locked Nucleic Acid Antagomirs Targeting miR-134 in Multiple Mouse and Rat Models of Epilepsy
Cristina R. Reschke,Luiz F. Almeida Silva,Braxton A. Norwood,Ketharini Senthilkumar,Gareth Morris,Amaya Sanz-Rodriguez,Ronán M. Conroy,Lara Costard,Valentin Neubert,Sebastian Bauer,Michael A. Farrell,Donncha F. O’Brien,Norman Delanty,Stephanie Schorge,R. Jeroen Pasterkamp,Felix Rosenow,David C. Henshall
Molecular Therapy - Nucleic Acids. 2017; 6: 45
[Pubmed] | [DOI]
52 MicroRNAs in injury and repair
Cory V. Gerlach,Vishal S. Vaidya
Archives of Toxicology. 2017;
[Pubmed] | [DOI]
53 Non-coding RNA Contribution to Thoracic and Abdominal Aortic Aneurysm Disease Development and Progression
Yuhuang Li,Lars Maegdefessel
Frontiers in Physiology. 2017; 8
[Pubmed] | [DOI]
54 miRNA-200c-3p is crucial in acute respiratory distress syndrome
Qiang Liu,Jianchao Du,Xuezhong Yu,Jun Xu,Fengming Huang,Xiaoyun Li,Cong Zhang,Xiao Li,Jiahui Chang,Daozhen Shang,Yan Zhao,Mingyao Tian,Huijun Lu,Jiantao Xu,Chang Li,Huadong Zhu,Ningyi Jin,Chengyu Jiang
Cell Discovery. 2017; 3: 17021
[Pubmed] | [DOI]
55 Positive radionuclide imaging of miRNA expression using RILES and the human sodium iodide symporter as reporter gene is feasible and supports a protective role of miRNA-23a in response to muscular atrophy
Viorel Simion,Julien Sobilo,Rudy Clemoncon,Sharuja Natkunarajah,Safia Ezzine,Florence Abdallah,Stephanie Lerondel,Chantal Pichon,Patrick Baril,Juri G. Gelovani
PLOS ONE. 2017; 12(5): e0177492
[Pubmed] | [DOI]
56 The roles of non-coding RNAs in cardiac regenerative medicine
Oi Kuan Choong,Desy S. Lee,Chen-Yun Chen,Patrick C.H. Hsieh
Non-coding RNA Research. 2017;
[Pubmed] | [DOI]
57 Regulatory role of microRNA on inflammatory responses of diabetic retinopathy
Eun-Ah Ye,JenaJ Steinle
Neural Regeneration Research. 2017; 12(4): 580
[Pubmed] | [DOI]
58 Dysregulated miRNAs and their pathogenic implications for the neurometabolic disease propionic acidemia
Ana Rivera-Barahona,Alejandro Fulgencio-Covián,Celia Pérez-Cerdá,Ricardo Ramos,Michael A. Barry,Magdalena Ugarte,Belén Pérez,Eva Richard,Lourdes R Desviat
Scientific Reports. 2017; 7(1)
[Pubmed] | [DOI]
59 New Dancing Couple: PD-L1 and MicroRNA
A. Grenda,P. Krawczyk
Scandinavian Journal of Immunology. 2017; 86(3): 130
[Pubmed] | [DOI]
60 Epigenetics in multiple myeloma: From mechanisms to therapy
Mohammad Alzrigat,Alba Atienza Párraga,Helena Jernberg-Wiklund
Seminars in Cancer Biology. 2017;
[Pubmed] | [DOI]
61 Role of microRNAs in obesity and obesity-related diseases
Giuseppe Iacomino,Alfonso Siani
Genes & Nutrition. 2017; 12(1)
[Pubmed] | [DOI]
62 Microvesicle-mediated delivery of miR-1343: impact on markers of fibrosis
Lindsay R. Stolzenburg,Ann Harris
Cell and Tissue Research. 2017;
[Pubmed] | [DOI]
63 A Concise Review of MicroRNA Exploring the Insights of MicroRNA Regulations in Bacterial, Viral and Metabolic Diseases
Ahsan Naveed,Sajjad ur-Rahman,Sabahat Abdullah,Muhammad Ammar Naveed
Molecular Biotechnology. 2017;
[Pubmed] | [DOI]
64 I?K-16 decreases miRNA-155 expression and attenuates the human monocyte inflammatory response
Norman James Galbraith,James Burton,Mathew Brady Ekman,Joseph Kenney,Samuel Patterson Walker,Stephen Manek,Campbell Bishop,Jane Victoria Carter,Sarah Appel Gardner,Hiram C. Polk,Partha Mukhopadhyay
PLOS ONE. 2017; 12(9): e0183987
[Pubmed] | [DOI]
65 miR-15a/miR-16 induces mitochondrial dependent apoptosis in breast cancer cells by suppressing oncogene BMI1
Nibedita Patel,Koteswara Rao Garikapati,M. Janaki Ramaiah,Kavi Kishor Polavarapu,Utpal Bhadra,Manika Pal Bhadra
Life Sciences. 2016;
[Pubmed] | [DOI]
66 Trying to understand the genetics of atopic dermatitis
Susanne Stemmler,Sabine Hoffjan
Molecular and Cellular Probes. 2016; 30(6): 374
[Pubmed] | [DOI]
67 MicroRNA-29b Overexpression Decreases Extracellular Matrix mRNA and Protein Production in Human Corneal Endothelial Cells
Tetsuya Toyono,Tomohiko Usui,Guadalupe Villarreal,Laura Kallay,Mario Matthaei,Lucas M. M. Vianna,Angela Y. Zhu,Masahiko Kuroda,Shiro Amano,Albert S. Jun
Cornea. 2016; 35(11): 1466
[Pubmed] | [DOI]
68 Excerpts from the 1st international NTNU symposium on current and future clinical biomarkers of cancer: innovation and implementation, June 16th and 17th 2016, Trondheim, Norway
Ana I. Robles,Karina Standahl Olsen,Dana W.T. Tsui,Vassilis Georgoulias,Jenette Creaney,Katalin Dobra,Mogens Vyberg,Nagahiro Minato,Robert A. Anders,Anne-Lise Børresen-Dale,Jianwei Zhou,Pål Sætrom,Boye Schnack Nielsen,Michaela B. Kirschner,Hans E. Krokan,Vassiliki Papadimitrakopoulou,Ioannis Tsamardinos,Oluf D. Røe
Journal of Translational Medicine. 2016; 14(1)
[Pubmed] | [DOI]
69 Therapeutic Resistance in Acute Myeloid Leukemia: The Role of Non-Coding RNAs
Armin Zebisch,Stefan Hatzl,Martin Pichler,Albert Wölfler,Heinz Sill
International Journal of Molecular Sciences. 2016; 17(12): 2080
[Pubmed] | [DOI]
70 MicroRNA-targeted therapeutics for lung cancer treatment
Jing Xue,Jiali Yang,Meihui Luo,William C. Cho,Xiaoming Liu
Expert Opinion on Drug Discovery. 2016; : 1
[Pubmed] | [DOI]



 

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