Displaying publications 1 - 20 of 116 in total

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  1. Plasma miR-146a and miR-365 expression and inflammatory factors in patients with osteoarthritis
    Wu W, Xuan Y, Ge Y, Mu S, Hu C, Fan R
    Malays J Pathol, 2021 Aug;43(2):311-317.
    PMID: 34448795
    OBJECTIVE: To investigate the expression levels of micro-ribonucleic acid (miR)-146a and miR-365 in the plasma of osteoarthritis (OA) patients, to study their expression with the inflammatory factors and the severity of disease in patients and to analyse their diagnostic significance.

    MATERIALS AND METHODS: A total of 42 OA patients diagnosed with OA and treated in our hospital from January 2017 to January 2018 were selected as the subjects, and 28 healthy people were enrolled as controls. The expressions of interleukin-1 beta (IL-1β) and IL-6 in the plasma of OA patients were detected via immunohistochemical staining. Moreover, the knee joint function of OA patients was evaluated by Lysholm score, Western Ontario and McMaster Universities (WOMAC) score and Visual Analogue Scale (VAS) score. The expression levels of plasma miR-146a and miR-365 in OA patients were measured through RT-PCR. Besides, the significance of the expression levels of miR-146a and miR-365 for the diagnosis of OA was analysed by ROC curves.

    RESULTS: As compared with healthy people, OA patients had elevated expression levels of plasma IL-1β and IL-6, decreased Lysholm score, increased WOMAC and VAS scores as well as significantly up-regulated levels of plasma miR-146a and miR-365, which were of important significance for diagnosis.

    CONCLUSION: The expression levels of plasma miR-146a, miR-365 and inflammatory factors are notably higher, the disease is more severe, and the function of knee joint movement is weaker in OA patients than those in healthy controls. It can be concluded that the levels of both miR-146a and miR-365 can serve as biomarkers of OA diagnosis.

    Matched MeSH terms: MicroRNAs/genetics*
  2. Fulltext IsomiRs have functional importance
    Tan GC, Dibb N
    Malays J Pathol, 2015 Aug;37(2):73-81.
    PMID: 26277662 MyJurnal
    Since the inception of deep sequencing, isomiRs are consistently observed to be produced by most miRNA genes in a variety of cell types. IsomiRs appear as a variation in length from the canonical sequence annotated in miRBase, due to an addition or deletion of one or more nucleotides at the 5(') or 3(') ends or both. As the seed sequence is located at the 5(') end of the microRNA, the target mRNA will be theoretically different. Therefore, 5(')isomiRs might potentially target a new set mRNA compared to their canonical counterpart. This article gives an overview of investigations that explored the functional potential of isomiRs such as their ability to incorporate into Argonaute protein, the differential expression of isomiRs in various tissue types and cell lines, and the differences of mRNA targets between isomiR and its canonical microRNA. In addition, this article provides a brief introduction of RNA sponges as a potential way to inhibit isomiRs.
    Matched MeSH terms: MicroRNAs/genetics*
  3. Fulltext Evaluation of extraction kits and RT-qPCR systems adapted to high-throughput platform for circulating miRNAs
    Tan GW, Khoo AS, Tan LP
    Sci Rep, 2015;5:9430.
    PMID: 25800946 DOI: 10.1038/srep09430
    MicroRNAs regulate gene expression at the post-transcriptional level. Differential expression of miRNAs can potentially be used as biomarkers for early diagnosis and prediction for outcomes. Failure in validation of miRNA profiles is often caused by variations in experimental parameters. In this study, the performance of five extraction kits and three RT-qPCR systems were evaluated using BioMark high-throughput platform and the effects of different experimental parameters on circulating miRNA levels were determined. Differences in the performance of extraction kits as well as varying accuracy, sensitivity and reproducibility in qPCR systems were observed. Normalisation of RT-qPCR data to spike-in controls can reduce extraction bias. However, the extent of correlation for different qPCR systems varies in different assays. At different time points, there was no significant fold change in eight of the plasma miRNAs that we evaluated. Higher level of miRNAs was detected in plasma as compared to serum of the same cohort. In summary, we demonstrated that high-throughput RT-qPCR with pre-amplification step had increased sensitivity and can be achieved with accuracy and high reproducibility through stringent experimental controls. The information provided here is useful for planning biomarker validation studies involving circulating miRNAs.
    Matched MeSH terms: MicroRNAs/genetics*
  4. MicroRNA pathways: an emerging role in identification of therapeutic strategies
    Vijayarathna S, Oon CE, Jothy SL, Chen Y, Kanwar JR, Sasidharan S
    Curr Gene Ther, 2014;14(2):112-20.
    PMID: 24588707
    For years researchers have exerted every effort to improve the influential roles of microRNA (miRNA) in regulating genes that direct mammalian cell development and function. In spite of numerous advancements, many facets of miRNA generation remain unresolved due to the perplexing regulatory networks. The biogenesis of miRNA, eminently endures as a mystery as no universal pathway defines or explicates the variegation in the rise of miRNAs. Early evidence in biogenesis ignited specific steps of being omitted or replaced that eventuate in the individual miRNAs of different mechanisms. Understanding the basic foundation concerning how miRNAs are generated and function will help with diagnostic tools and therapeutic strategies. This review encompasses the canonical and the non-canonical pathways involved in miRNA biogenesis, while elucidating how miRNAs regulate genes at the nuclear level and also the mechanism that lies behind circulating miRNAs.
    Matched MeSH terms: MicroRNAs/genetics*
  5. MicroRNAs horizon in retinoblastoma
    Mirakholi M, Mahmoudi T, Heidari M
    Acta Med Iran, 2013;51(12):823-9.
    PMID: 24442535
    In the retinoblastoma research, it is of great interest to identify molecular markers associated with the genetics of tumorigenesis. microRNAs (miRNAs) are small non-coding RNA molecules that play a regulatory role in many crucial cellular pathways such as differentiation, cell cycle progression, and apoptosis. A body of evidences showed dysregulation of miRNAs in tumor biology and many diseases. They potentially play a significant role in tumorigenesis processes and have been the subject of research in many types of cancers including retinal tumorigenesis. miRNA expression profiling was found to be associated with tumor development, progression and treatment. These associations demonstrate the putative applications of miRNAs in monitoring of different aspect of tumors consisting diagnostic, prognostic and therapeutic. Herein, we review the current literature concerning to the study of miRNA target recognition, function to tumorigenesis and treatment in retinoblastoma. Identification the specific miRNA biomarkers associated with retinoblastoma cancer may help to establish new therapeutic approaches for salvage affected eyes in patients.
    Matched MeSH terms: MicroRNAs/genetics
  6. PLASMA MICRORNA-133А LEVEL IN PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION
    Koval S, Snihurska I, Yushko K, Lytvynova O, Berezin A
    Georgian Med News, 2019 May.
    PMID: 31322515
    The aim of research was to investigate the plasma microRNA (miR-133а) level in patients with essential arterial hypertension (EAH). A total of 45 patients with EAH 2-3 degrees aged 52.14 ± 8.25 years and 21 healthy individuals (control group) with comparable age and sex distributions. The following frequency of risk factors was revealed among the examined patients: overweight (53%), dyslipidaemia (73%), pre-diabetes (13%), asymptomatic hyperuricemia (29%); hypertension-mediated organ damage: increased arterial stiffness (27%), left ventricular hypertrophy (55%), atherosclerotic plaque in the carotid artery (40%), microalbuminuria (15%), moderate stage of chronic kidney disease (22%) and cardiovascular diseases: stable ischemic heart disease (11%) and heart failure with preserved ejection fraction of NYHA functional class I (18%). The plasma miR-133a level was determined by polymerase chain reaction using "CFX96 Touch" detection system (BioRad) and "TaqMan microRNA Assay" and "TaqMan® Universal PCR Master Mix" reagents (Thermo Fisher Scientific, USA). It has been established that in patients with EAH the plasma level of miR-133a was significantly lower than in practically healthy individuals (0,182 [0,102; 0,301] ), vs (0,382 [0,198; 0,474]), p <0.05). It has also been revealed a significant decrease in the level of miR-133a in the blood plasma in patients with such organs damage as LVH (0,133 [0,099;0,184]) in comparison with patients without LVH (0,238 [0,155; 0,410]), p <0.05) and also significantly lower than in healthy subjects in the control group (0,382 [0,198; 0,474]), p<0.05). There were no statistically significant differences in the plasma levels of miR-133a in the group of patients with EAH, depending on the presence of risk factors, other organ damage and cardiovascular diseases. The findings suggest the significant role of reducing of plasma levels of miR-133a in the pathogenesis of hypertension itself and in pathological remodeling of the heart.
    Matched MeSH terms: MicroRNAs/genetics
  7. Association of Micro RNA and Postoperative Cognitive Dysfunction: A Review
    Yazit NAA, Juliana N, Das S, Teng NIMF, Fahmy NM, Azmani S, et al.
    Mini Rev Med Chem, 2020;20(17):1781-1790.
    PMID: 32564754 DOI: 10.2174/1389557520666200621182717
    Postoperative Cognitive Dysfunction (POCD) refers to the condition of neurocognitive decline following surgery in a cognitive and sensory manner. There are several risk factors, which may be life-threatening for this condition. Neuropsychological assessment of this condition is very important. In the present review, we discuss the association of apolipoprotein epsilon 4 (APOE ε4) and few miRNAs with POCD, and highlight the clinical importance for prognosis, diagnosis and treatment of POCD. Microarray is a genome analysis that can be used to determine DNA abnormalities. This current technique is rapid, efficient and high-throughout. Microarray techniques are widely used to diagnose diseases, particularly in genetic disorder, chromosomal abnormalities, mutations, infectious diseases and disease-relevant biomarkers. MicroRNAs (miRNAs) are a class of non-coding RNAs that are widely found distributed in eukaryotes. Few miRNAs influence the nervous system development, and nerve damage repair. Microarray approach can be utilized to understand the miRNAs involved and their pathways in POCD development, unleashing their potential to be considered as a diagnostic marker for POCD. This paper summarizes and identifies the studies that use microarray based approaches for POCD analysis. Since the application of microarray in POCD is expanding, there is a need to review the current knowledge of this approach.
    Matched MeSH terms: MicroRNAs/genetics
  8. Downregulation of human choline kinase α gene expression by miR-876-5p
    Ayub Khan SM, Few LL, See Too WC
    Mol Med Rep, 2018 May;17(5):7442-7450.
    PMID: 29568919 DOI: 10.3892/mmr.2018.8762
    Choline kinase (CK) is the first enzyme in the CDP-choline pathway for the synthesis of phosphatidylcholine, the most abundant phospholipid in the mammalian cell membrane. This enzyme exists as three isozymes (α1, α2 and β) and the CKα isozyme has been implicated in cancer pathogenesis. Inhibition of CK activity has been proposed for cancer therapies. MicroRNAs (miRNAs/miRs) are non‑coding RNAs that serve important roles in diverse biological pathways and human diseases, including cancer. However, the regulation of CKα gene expression by miRNAs has never been investigated, to the best of the authors' knowledge. In the present study, two miRNA mimics, miR‑876‑5p and miR‑646, were transfected into the HepG2 cell line and the effect of these miRNAs on the levels of CKα mRNA were determined by reverse transcription‑quantitative polymerase chain reaction. Cells transfected with 25 nM miR‑876‑5p for 48 h exhibited significantly lower levels of CKα mRNA. Following optimization, miR‑876‑5p caused four times lower levels of CKα mRNA compared to the negative control. Effects of the miRNAs on HepG2 cell viability and cellular morphology were additionally analyzed using an MTT cell viability assay and scanning electron microscopy, respectively. HepG2 cells that were transfected with the optimum concentration of miR‑876‑5p for the optimum duration exhibited 25% lower viability than negative control and signs of apoptosis in electron micrographs. The results suggested miR‑876‑5p as a potential miRNA modulator of CKα expression in the cells, and may be relevant for the design of more effective anticancer strategy targeting CK.
    Matched MeSH terms: MicroRNAs/genetics*
  9. microRNAs expression profiles in Schistosoma japonicum of different sex 14 and 28 days post-infection
    Ai L, Hu W, Zhang RL, Huang DN, Chen SH, Xu B, et al.
    Trop Biomed, 2020 Dec 01;37(4):947-962.
    PMID: 33612748 DOI: 10.47665/tb.37.4.947
    Different miRNAs are involved in the life cycles of Schistosoma japonicum. The aim of this study was to examine the expression profile of miRNAs in individual S. japonicum of different sex before and after pairing (18 and 24 dpi). The majority of differential expressed miRNAs were highly abundant at 14 dpi, except for sja-miR-125b and sja-miR-3505, in both male and female. Moreover, it was estimated that sja-miR-125b and sja-miR-3505 might be related to laying eggs. sja-miR-2a-5p and sja-miR-3484-5p were expressed at 14 dpi in males and were significantly clustered in DNA topoisomerase III, Rap guanine nucleotide exchange factor 1 and L-serine/L-threonine ammonia-lyase. Target genes of sja-miR-2d-5p, sja-miR-31- 5p and sja-miR-125a, which were expressed at 14 dpi in males but particularly females, were clustered in kelch-like protein 12, fructose-bisphosphate aldolase, class I, and heat shock protein 90 kDa beta. Predicted target genes of sja-miR-3483-3p (expressed at 28 dpi in females but not in males) were clustered in 26S proteasome regulatory subunit N1, ATPdependent RNA helicase DDX17. Predicted target genes of sja-miR-219-5p, which were differentially expressed at 28 dpi in females but particularly males, were clustered in DNA excision repair protein ERCC-6, protein phosphatase 1D, and ATPase family AAA domaincontaining protein 3A/B. Moreover, at 28 dpi, eight miRNAs were significantly up-regulated in females compared to males. The predicted target genes of these miRNAs were significantly clustered in heat shock protein 90 kDa beta, 26S proteasome regulatory subunit N1, and protein arginine N-methyltransferase 1. To sum up, differentially expressed miRNAs may have an essential role and provide necessary information on clarifying this trematode's growth, development, maturation, and infection ability to mammalian hosts in its complex life cycle, and may be helpful for developing new drug targets and vaccine candidates for schistosomiasis.
    Matched MeSH terms: MicroRNAs/genetics*
  10. Fulltext Drought Response in Rice: The miRNA Story
    Nadarajah K, Kumar IS
    Int J Mol Sci, 2019 Aug 01;20(15).
    PMID: 31374851 DOI: 10.3390/ijms20153766
    As a semi-aquatic plant, rice requires water for proper growth, development, and orientation of physiological processes. Stress is induced at the cellular and molecular level when rice is exposed to drought or periods of low water availability. Plants have existing defense mechanisms in planta that respond to stress. In this review we examine the role played by miRNAs in the regulation and control of drought stress in rice through a summary of molecular studies conducted on miRNAs with emphasis on their contribution to drought regulatory networks in comparison to other plant systems. The interaction between miRNAs, target genes, transcription factors and their respective roles in drought-induced stresses is elaborated. The cross talk involved in controlling drought stress responses through the up and down regulation of targets encoding regulatory and functional proteins is highlighted. The information contained herein can further be explored to identify targets for crop improvement in the future.
    Matched MeSH terms: MicroRNAs/genetics*
  11. Fulltext Cross-Kingdom Regulation by Plant microRNAs Provides Novel Insight into Gene Regulation
    Samad AFA, Kamaroddin MF, Sajad M
    Adv Nutr, 2021 Feb 01;12(1):197-211.
    PMID: 32862223 DOI: 10.1093/advances/nmaa095
    microRNAs (miRNAs) are well known as major players in mammalian and plant genetic systems that act by regulating gene expression at the post-transcriptional level. These tiny molecules can regulate target genes (mRNAs) through either cleavage or translational inhibition. Recently, the discovery of plant-derived miRNAs showing cross-kingdom abilities to regulate mammalian gene expression has prompted exciting discussions among researchers. After being acquired orally through the diet, plant miRNAs can survive in the digestive tract, enter the circulatory system, and regulate endogenous mRNAs. Here, we review current knowledge regarding the cross-kingdom mechanisms of plant miRNAs, related controversies, and potential applications of these miRNAs in dietary therapy, which will provide new insights for plant miRNA investigations related to health issues in humans.
    Matched MeSH terms: MicroRNAs/genetics
  12. Fulltext Association between MIR499A rs3746444 polymorphism and breast cancer susceptibility: a meta-analysis
    Tan SC, Lim PY, Fang J, Mokhtar MFM, Hanif EAM, Jamal R
    Sci Rep, 2020 Feb 26;10(1):3508.
    PMID: 32103099 DOI: 10.1038/s41598-020-60442-3
    Numerous studies have investigated the association of MIR499A rs3746444 polymorphism with breast cancer susceptibility, but the results have been inconsistent. In this work, we performed a meta-analysis to obtain a more reliable estimate of the association between the polymorphism and susceptibility to breast cancer. A comprehensive literature search was conducted on PubMed, Scopus, Web of Science (WoS), China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases up to January 2020. A total of 14 studies involving 6,797 cases and 8,534 controls were included for analysis under five genetic models: homozygous (GG vs. AA), heterozygous (AG vs. AA), dominant (AG + GG vs. AA), recessive (GG vs. AA + AG) and allele (G vs. A). A statistically significant association was observed between the polymorphism and an increased breast cancer susceptibility under all genetic models (homozygous, OR = 1.33, 95% CI = 1.03-1.71, P = 0.03; heterozygous, OR = 1.08, 95% CI = 1.00-1.16, P = 0.04; dominant, OR = 1.15, 95% CI = 1.02-1.30; P = 0.03; recessive, OR = 1.35, 95% CI = 1.06-1.72, P = 0.01; allele, OR = 1.12, 95% CI = 1.00-1.26, P = 0.04). Subgroup analysis based on ethnicity suggested that significant association was present only among Asians, but not Caucasians. In conclusion, MIR499A rs3746444 polymorphism was significantly associated with breast cancer susceptibility among Asians, suggesting its potential use as a genetic risk marker in this population.
    Matched MeSH terms: MicroRNAs/genetics*
  13. Fulltext The Regulatory Role of MicroRNAs in Breast Cancer
    Loh HY, Norman BP, Lai KS, Rahman NMANA, Alitheen NBM, Osman MA
    Int J Mol Sci, 2019 Oct 06;20(19).
    PMID: 31590453 DOI: 10.3390/ijms20194940
    MicroRNAs (miRNAs) are small non-coding RNA molecules which function as critical post-transcriptional gene regulators of various biological functions. Generally, miRNAs negatively regulate gene expression by binding to their selective messenger RNAs (mRNAs), thereby leading to either mRNA degradation or translational repression, depending on the degree of complementarity with target mRNA sequences. Aberrant expression of these miRNAs has been linked etiologically with various human diseases including breast cancer. Different cellular pathways of breast cancer development such as cell proliferation, apoptotic response, metastasis, cancer recurrence and chemoresistance are regulated by either the oncogenic miRNA (oncomiR) or tumor suppressor miRNA (tsmiR). In this review, we highlight the current state of research into miRNA involved in breast cancer, with particular attention to articles published between the years 2000 to 2019, using detailed searches of the databases PubMed, Google Scholar, and Scopus. The post-transcriptional gene regulatory roles of various dysregulated miRNAs in breast cancer and their potential as therapeutic targets are also discussed.
    Matched MeSH terms: MicroRNAs/genetics*
  14. Fulltext Horseshoe crab genomes reveal the evolution of genes and microRNAs after three rounds of whole genome duplication
    Nong W, Qu Z, Li Y, Barton-Owen T, Wong AYP, Yip HY, et al.
    Commun Biol, 2021 01 19;4(1):83.
    PMID: 33469163 DOI: 10.1038/s42003-020-01637-2
    Whole genome duplication (WGD) has occurred in relatively few sexually reproducing invertebrates. Consequently, the WGD that occurred in the common ancestor of horseshoe crabs ~135 million years ago provides a rare opportunity to decipher the evolutionary consequences of a duplicated invertebrate genome. Here, we present a high-quality genome assembly for the mangrove horseshoe crab Carcinoscorpius rotundicauda (1.7 Gb, N50 = 90.2 Mb, with 89.8% sequences anchored to 16 pseudomolecules, 2n = 32), and a resequenced genome of the tri-spine horseshoe crab Tachypleus tridentatus (1.7 Gb, N50 = 109.7 Mb). Analyses of gene families, microRNAs, and synteny show that horseshoe crabs have undergone three rounds (3R) of WGD. Comparison of C. rotundicauda and T. tridentatus genomes from populations from several geographic locations further elucidates the diverse fates of both coding and noncoding genes. Together, the present study represents a cornerstone for improving our understanding of invertebrate WGD events on the evolutionary fates of genes and microRNAs, at both the individual and population level. We also provide improved genomic resources for horseshoe crabs, of applied value for breeding programs and conservation of this fascinating and unusual invertebrate lineage.
    Matched MeSH terms: MicroRNAs/genetics*
  15. MicroRNAs: association with radioresistant and potential uses of natural remedies as green gene therapeutic approaches
    Jothy SL, Chen Y, Vijayarathna S, Kanwar JR, Sasidharan S
    Curr Gene Ther, 2015;15(1):15-20.
    PMID: 25478696
    Radiotherapy plays an essential primary role in cancer patients. Regardless of its significant advances in treatment options, tumor recurrence and radio-resistance in cancer cells still occur in a high percentage of patients. Furthermore, the over expression of miRNAs accompanies the development of radio-resistant cancer cells. Consequently, miRNAs might serve as therapeutic targets for the treatment of radio-resistance in cancer cells. The findings of the current research also signify that the use of a natural anti-miRNA substance could inhibit specific miRNAs, and, concurrently, these natural remedies could exhibit radioprotective activity against the healthy cells during radiotherapy. Therefore, in this review, we have reported the association of miRNAs with radio-resistance and the potential uses of natural remedies as green gene therapeutic approaches, as well as radioprotectors against the adverse effects of irradiation on healthy cells during radiotherapy.
    Matched MeSH terms: MicroRNAs/genetics*
  16. Role of miRNA in head and neck squamous cell carcinoma
    Masood Y, Kqueen CY, Rajadurai P
    Expert Rev Anticancer Ther, 2015 Feb;15(2):183-97.
    PMID: 25367254 DOI: 10.1586/14737140.2015.978294
    Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Evidence suggests that miRNAs play an important role in progression, recurrence, metastasis and postoperative survival of HNSCC. Studies have investigated the utility of miRNAs as diagnostic/prognostic tools and as potential therapeutic targets and biomarkers that may improve the management and outcomes of HNSCC. The aim of this article is to review the current literature on aberrant expression profiles of miRNAs in biopsy samples of HNSCC and their role in cancer development, metastasis, prognosis and survival of these patients. This review gives an overview that miRNAs deregulation play major role in the development of HNSCC. They offer the potential to be used as biomarkers or novel therapeutic targets. Future research is required to test their use in both of these fields.
    Matched MeSH terms: MicroRNAs/genetics*
  17. Fulltext Frequent co-expression of miRNA-5p and -3p species and cross-targeting in induced pluripotent stem cells
    Huang CJ, Nguyen PN, Choo KB, Sugii S, Wee K, Cheong SK, et al.
    Int J Med Sci, 2014;11(8):824-33.
    PMID: 24936146 DOI: 10.7150/ijms.8358
    A miRNA precursor generally gives rise to one major miRNA species derived from the 5' arm, and are called miRNA-5p. However, more recent studies have shown co-expression of miRNA-5p and -3p, albeit in different concentrations, in cancer cells targeting different sets of transcripts. Co-expression and regulation of the -5p and -3p miRNA species in stem cells, particularly in the reprogramming process, have not been studied.
    Matched MeSH terms: MicroRNAs/genetics
  18. Coaxing cancer pro-apoptoticity: an approach blending therapeutic miRNAs and dietary phytochemicals
    Vijayarathna S, Sasidharan S
    Asian Pac J Cancer Prev, 2014;15(13):5499-500.
    PMID: 25041025
    Matched MeSH terms: MicroRNAs/genetics*
  19. MicroRNAs: biogenesis, roles for carcinogenesis and as potential biomarkers for cancer diagnosis and prognosis
    Kavitha N, Vijayarathna S, Jothy SL, Oon CE, Chen Y, Kanwar JR, et al.
    Asian Pac J Cancer Prev, 2014;15(18):7489-97.
    PMID: 25292018
    MicroRNAs (miRNAs) are short non-coding RNAs of 20-24 nucleotides that play important roles in carcinogenesis. Accordingly, miRNAs control numerous cancer-relevant biological events such as cell proliferation, cell cycle control, metabolism and apoptosis. In this review, we summarize the current knowledge and concepts concerning the biogenesis of miRNAs, miRNA roles in cancer and their potential as biomarkers for cancer diagnosis and prognosis including the regulation of key cancer-related pathways, such as cell cycle control and miRNA dysregulation. Moreover, microRNA molecules are already receiving the attention of world researchers as therapeutic targets and agents. Therefore, in-depth knowledge of microRNAs has the potential not only to identify their roles in cancer, but also to exploit them as potential biomarkers for cancer diagnosis and identify therapeutic targets for new drug discovery.
    Matched MeSH terms: MicroRNAs/genetics*
  20. Fulltext 5' isomiR variation is of functional and evolutionary importance
    Tan GC, Chan E, Molnar A, Sarkar R, Alexieva D, Isa IM, et al.
    Nucleic Acids Res, 2014 Aug;42(14):9424-35.
    PMID: 25056318 DOI: 10.1093/nar/gku656
    We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3' and/or 5' end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5' differences and in support of this we report that a 5' isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5' isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes.
    Matched MeSH terms: MicroRNAs/genetics
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