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mirna and long non-coding rna: molecular function and clinical value in breast and ovarian cancers

EXPERT REVIEW OF MOLECULAR DIAGNOSTICS 2018年第11期18卷 963-979页

作者： Panoutsopoulou, Konstantina Avgeris, Margaritis Scorilas, Andreas Natl & Kapodistrian Univ Athens Dept Biochem & Mol Biol Fac Biol Athens 15701 Greece

Introduction: The elucidation of tumor molecular hallmarks and the identification of novel molecular markers are of first translational priority in breast and ovarian cancer research, aiming to support personalized disease treatment and monitoring decisions. Recent high-throughput studies have revealed that 80% of the genome is transcribed into rnas without protein-coding potential, namely non-coding rnas (ncrnas), challenging the concept of 'junk DNA'. Undoubtedly, micrornas (mirnas) and long non-coding rnas (lncrnas) represent the best-studied family classes, emerging as the most powerful gene-expression regulators at epigenetic, transcriptional and post-transcriptional levels. Areas covered: Cancer research has highlighted the active implication of ncrnas, most notably of mirnas and lncrnas, in almost every aspect of the cancer cells' biology as well as their deregulated expression in both breast and ovarian tumors. In the present manuscript we discuss the existing knowledge regarding the involvement of mirnas and lncrnas in the molecular background of breast and ovarian malignancies, to highlight their clinical utility in improving disease management. Expert commentary: mirnas and lncrnas represent central mediators of cancer cells' phenotype, and promising molecular markers and therapeutic targets to support precision medicine in breast and ovarian cancers.

关键词： microrna lncrna non coding rna ovarian cancer breast cancer

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non-coding rna: a novel opportunity for the personalized treatment of multiple myeloma

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EXPERT OPINION ON BIOLOGICAL THERAPY 2013年第Sup1期13卷 S125-S137页

作者： Amodio, Nicola Di Martino, Maria Teresa Neri, Antonino Tagliaferri, Pierosandro Tassone, Pierfrancesco Magna Graecia Univ Catanzaro I-88100 Catanzaro Italy T Campanella Canc Ctr Dept Expt & Clin Med Med Oncol Unit I-88100 Catanzaro Italy Univ Milan Dept Clin Sci & Community Hlth IRCCS Policlin Fdn Milan Italy Temple Univ Coll Sci & Technol Ctr Biotechnol Sbarro Inst Canc Res & Mol Med Philadelphia PA 19122 USA

Introduction: Increasing evidence indicates that non-coding rnas (ncrnas) are aberrantly expressed and/or functionally deregulated in hematological malignancies, including multiple myeloma. Harnessing these abnormalities by either replacing or inhibiting ncrnas is emerging as novel therapeutic option. Areas covered: We review the recent remarkable advancement in the understanding of the biological functions of human ncrnas in multiple myeloma, including the biogenesis, the mechanisms of expression, the relevance as biomarkers, and mostly, the therapeutic potential. Special emphasis is given to micrornas, the best characterized class of ncrnas. Expert opinion: An improved understanding of the role of ncrnas in multiple myeloma would provide valuable information about key cancer-promoting pathways and might be highly useful for diagnostic and prognostic assessments. This knowledge might also lead to advancement in the management of multiple myeloma through the development of novel personalized ncrna-based therapies.

关键词： microrna mirna mirna therapeutics multiple myeloma non coding rna

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Abundant class of non-coding rna regulates development in the social amoeba Dictyostelium discoideum

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rna BIOLOGY 2011年第6期8卷 1094-1104页

作者： Avesson, Lotta Schumacher, Heiko T. Fechter, Pierre Romby, Pascale Hellman, Ulf Soderbom, Fredrik Swedish Univ Agr Sci Dept Mol Biol Uppsala Sweden Uppsala Univ Biomed Ctr Ludwig Inst Canc Res Ltd Uppsala Sweden Univ Strasbourg CNRS IBMC Architecture & React ARN Strasbourg France

non-coding (nc)rnas are important players in most biological processes. Although small rnas such as micrornas and small interfering rnas have emerged as exceptionally important regulators of gene expression, great numbers of larger ncrnas have also been identified. Many of these are abundant and differentially expressed but their functions have in most cases not been elucidated. The social amoeba Dictyostelium discoideum contain the ncrnas commonly found in eukaryotes. In addition, we previously reported the identification of two novel classes of 42-65 nt long stem-loop forming rnas, Class I and Class II rnas, with unknown function. In this study we have further characterized these abundant ncrnas, which are downregulated during development. We have confirmed expression of 29 Class I rnas and experimentally verified the formation of the computationally predicted short conserved stem structure. Furthermore, we have for the first time created knockout strains for several small ncrna genes in D. discoideum and found that deletion of one of the Class I rnas, DdR-21, results in aberrant development. In addition we have shown that this Class I rna forms a complex with one or several proteins but do not appear to be associated with ribosomes or polysomes. In a pull down assay, several proteins interacting with DdR-21 were identified, one of these has two rna recognition motifs (RRMs). The purified RRM containing protein was demonstrated to bind directly and specifically to DdR-21.

关键词： non coding rna rna-binding protein regulation Dictyostelium discoideum development gene knockout

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cncrnas: Bi-functional rnas with protein coding and non-coding functions

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SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY 2015年 47-48卷 40-51页

作者： Kumari, Pooja Sampath, Karuna Univ Warwick Warwick Med Sch Div Biomed Cell Biol Coventry CV4 7AJ W Midlands England

For many decades, the major function of mrna was thought to be to provide protein-coding information embedded in the genome. The advent of high-throughput sequencing has led to the discovery of pervasive transcription of eukaryotic genomes and opened the world of rna-mediated gene regulation. Many regulatory rnas have been found to be incapable of protein coding and are hence termed as non-coding rnas (ncrnas). However, studies in recent years have shown that several previously annotated noncoding rnas have the potential to encode proteins, and conversely, some coding rnas have regulatory functions independent of the protein they encode. Such bi-functional rnas, with both protein coding and non-coding functions, which we term as 'cncrnas', have emerged as new players in cellular systems. Here, we describe the functions of some cncrnas identified from bacteria to humans. Because the functions of many rnas across genomes remains unclear, we propose that rnas be classified as coding, non-coding or both only after careful analysis of their functions. (C) 2015 The Authors. Published by Elsevier Ltd.

关键词： cncrnas Bi-functional rna non coding rna Protein coding Regulatory rna rna structure rna processing Dual function rna

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The Impact of mirnas on the Efficacy of Tamoxifen in Breast Cancer Treatment: A Systematic Review

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CLINICAL BREAST CANCER 2024年第4期24卷 341-350页

作者： Kavishahi, Nima Nikbin Rezaee, Aryan Jalalian, Sara Shahid Sadoughi Univ Med Sci Student Res Comm Sch Med Dept Med Genet Yazd Iran Iran Univ Med Sci Student Res Comm Sch Med Tehran Iran North Khorasan Univ Med Sci Student Res Comm Sch Med Bojnurd Iran

Seventy percent of breast cancer patients have an active estrogen receptor. Tamoxifen interferes with estrogen's ability to bind to cancer cells. The most challenging aspect of tamoxifen, however, is that breast cancer cells become resistant to its effects. Some studies have shown that alterations in mirna expression contribute significantly to drug resistance in breast cancer. Therefore, the present systematic review aims to investigate mirnas that significantly influence the response to tamoxifen treatment. The present study follows the PRISMA instructions. The Web of Science, PubMed, and Scopus databases were searched to retrieve English articles. The searches were conducted up to September 11, 2022. The search strategy included the terms "Tamoxifen", "Breast Neoplasm", and "Microrna". The inclusion cr iter ia of this study are English, original, and experimental studies investigating mirnas that are effective in the treatment efficacy of tamoxifen. A total of 565 articles were retrieved. After screening, 75 studies met our inclusion criteria. This systematic review study examined 105 mirnas, of which 44 have a positive effect, and 47 mirnas inhibit tamoxifen function. Fourteen mirnas have a controversial effect, ie, some studies show positive and negative effects. The study of mirnas affecting tamoxifen function in breast cancer patients may facilitate the identification of individuals at higher risk of disease recurrence. Conversely, it can potentially utilize appropriate interventions to defeat drug resistance effectively.

关键词： Estrogen receptor non coding rna Mammary carcinoma Chemotherapy Resistance

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The importance of mirnas and epigenetics in acute lymphoblastic leukemia prognosis

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JOUrnaL OF CELLULAR PHYSIOLOGY 2019年第4期234卷 3216-3230页

作者： Ranjbar, Reza Karimian, Ansar Fard, Arad Aghaie Tourani, Mehdi Majidinia, Maryam Jadidi-Niaragh, Farhad Yousefi, Bahman Baqiyatallah Univ Med Sci Mol Biol Res Ctr Tehran Iran Babol Univ Med Sci Hlth Res Inst Cellular & Mol Biol Res Ctr Babol Sar Iran Kurdistan Univ Med Sci Canc & Immunol Res Ctr Sanandaj Iran Babol Univ Med Sci Student Res Comm Babol Sar Iran Tarbiat Modares Univ Fac Med Sci Dept Hematol Tehran Iran Urmia Univ Med Sci Solid Tumor Res Ctr Orumiyeh Iran Tabriz Univ Med Sci Immunol Res Ctr Tabriz Iran Tabriz Univ Med Sci Mol Med Res Ctr Tabriz Iran Tabriz Univ Med Sci Drug Appl Res Ctr Tabriz Iran

Acute lymphoblastic leukemia (ALL), one of the most common malignant human disorders, originates in different important genetic lesions in T-cell or B-cell progenitors. ALL is a malignant lymphoid progenitor with peak prevalence in children (2-5 years). The rate of survival when one is suffering from ALL depends on various agents including the age of the patient, responses to anti-leukemic therapy, and cell biology. mirnas and epigenetics are important regulatory factors in the expression of genes. mirnas are noncoding rna with inhibitory effectors on specific mrna. Patterns of DNA methylation are profoundly changed in ALL by epigenetic mechanisms. The deciphering of mirna and the epigenetic pathogenesis in ALL could revolutionize response to the therapy and outcome, and create an enormous promise for novel approaches to reduce the toxic side-effects of intensive leukemia. Hence, pathogenetic mirnas and epigenetics leading to the initiation and the progression of ALL are summarized in this review.

关键词： epigenetics leukemia non coding rna

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Circulating exosomal mirnas: clinical significance in human cancers

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EXPERT REVIEW OF MOLECULAR DIAGNOSTICS 2019年第11期19卷 979-995页

作者： Avgeris, Margaritis Panoutsopoulou, Konstantina Papadimitriou, Maria-Alexandra Scorilas, Andreas Natl & Kapodistrian Univ Athens Fac Biol Dept Biochem & Mol Biol Athens 15701 Greece

Introduction: The identification of novel noninvasive biomarkers to ameliorate early-diagnosis, and disease prognosis, as well as to support personalized treatment and monitoring decisions is of first clinical priority for cancer patients? care. Exosomes are natural endosome-derived extracellular vesicles that have emerged as crucial mediators of intercellular communication and tumor progression. Considering that deregulated mirna levels have been described in numerous human malignancies and that tumor-derived exosomes reflect mirna expression of donor tumor cells, the evaluation of exosome-derived circulating mirnas (exomiRs) may offer a new promising class of noninvasive molecular markers to improve patients? management and quality-of-life. Areas covered: In the current review we have summarized the existing knowledge on the clinical relevance of circulating exosomal mirnas in improving cancer diagnosis and prognosis, and thus supporting personalized patients? management Expert commentary: Cancer research has highlighted the abundance of exomiRs in patients? plasma and serum samples, as well as their biomarker capabilities in the vast majority of human malignancies studied so far. Their analytical stability constitutes exomiRs ideal molecular markers to overcome numerous limitations of cancer clinical management, while future large-scale studies should unveil exomiRs translational utility in modern cancer molecular diagnostics.

关键词： Circulating mirna exomiR exosomes non coding rna noninvasive biomarkers

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Microrna-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2)

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2010年第49期107卷 21098-21103页

作者： Valeri, Nicola Gasparini, Pierluigi Braconi, Chiara Paone, Alessio Lovat, Francesca Fabbri, Muller Sumani, Khlea M. Alder, Hansjuerg Amadori, Dino Patel, Tushar Nuovo, Gerard J. Fishel, Richard Croce, Carlo M. Ohio State Univ Dept Mol Virol Immunol & Med Genet Columbus OH 43210 USA Ohio State Univ Dept Internal Med Columbus OH 43210 USA Ohio State Univ Dept Pathol Columbus OH 43210 USA Ohio State Univ Dept Phys Columbus OH 43210 USA Ohio State Univ Ctr Comprehens Canc Columbus OH 43210 USA Univ Ferrara Dept Embryol & Morphol I-44011 Ferrara Italy Univ Ferrara Dept Expt & Diagnost Med I-44011 Ferrara Italy Ist Sci Romagnolo Studio & Cura Tumori I-47014 Meldola Italy

The overexpression of microrna-21 (miR-21) is linked to a number of human tumors including colorectal cancer, where it appears to regulate the expression of tumor suppressor genes including p21, phosphatase and tensin homolog, TGF beta receptor II, and B-cell leukemia/lymphoma 2 -associated X protein. Here we demonstrate that miR-21 targets and down-regulates the core mismatch repair (MMR) recognition protein complex, human mutS homolog 2 (hMSH2) and 6 (hMSH6). Colorectal tumors that express a high level of miR-21 display reduced hMSH2 protein expression. Cells that overproduce miR-21 exhibit significantly reduced 5-fluorouracil (5-FU)-induced G2/M damage arrest and apoptosis that is characteristic of defects in the core MMR component. Moreover, xenograft studies demonstrate that miR-21 overexpression dramatically reduces the therapeutic efficacy of 5-FU. These studies suggest that the down-regulation of the MMR mutator gene associated with miR-21 overexpression may be an important clinical indicator of therapeutic efficacy in colorectal cancer.

关键词： colon cancer non coding rna DNA repair

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Cascade transcription of mrna-type long non-coding rnas (mlonrnas) and local chromatin remodeling

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EPIGENETICS 2009年第1期4卷 5-7页

作者： Hirota, Kouji Ohta, Kunihiro Kyoto Univ Grad Sch Med Dept Radiat Genet Sakyo Ku Kyoto 6068501 Japan Univ Tokyo Grad Sch Arts & Sci Dept Life Sci Meguro Ku Tokyo Japan

Eukaryotic transcriptome analyses have revealed the presence of a huge number of mrna-type non-coding rnas (ncrnas). Expression of them is often developmentally regulated, but little is known about their function. We have recently demonstrated that cascade of rna polymerase II (rnaPII)-mediated transcription initiation of such mrna-type long ncrnas (mlonrna) results in stepwise disruption of local chromatin structure at the fission yeast Schizosaccharomyces pombe fbp1(+) locus during transcriptional activation upon glucose derepression. Similar transition of rna transcripts coupled with local chromatin alteration is observed meiotically in the fission yeast recombination hotspot ade6-M26. Here, we hypothesize that rnaPII transcription of mlonrnas disrupts chromatin array. This idea may provide a new clue to understand why so many species of ncrnas are expressed in eukaryotic cells.

关键词： mlonrna non coding rna pioneer polymerase chromatin remodeling transcription

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Lncrnas expression profile in peripheral blood mononuclear cells from multiple sclerosis patients

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JOUrnaL OF NEUROIMMUNOLOGY 2018年 324卷 129-135页

作者： Fenoglio, Chiara Oldoni, Emanuela Serpente, Maria De Riz, Milena A. Arcaro, Marina D'Anca, Marianna Pietroboni, Anna M. Calvi, Alberto Lecchi, Elisabetta Goris, An Mallants, Klara Dubois, Benedicte Comi, Cristoforo Cantello, Roberto Scarpini, Elio Galimberti, Daniela Univ Milan Dino Ferrari Ctr Milan Italy Katholieke Univ Leuven Dept Neurosci Lab Neuroimmunol Herestr 49 Bus 1022 B-3000 Leuven Belgium Fdn IRCCS Ca Granda Osped Maggiore Policlin Neurodegenerat Dis Unit Milan Italy Univ Hosp Leuven Dept Neurol Herestr 49 B-3000 Leuven Belgium Univ Eastern Piedmont Amedeo Avogadro Sect Neurol Dept Translat Med Novara Italy

Lncrna PCR arrays containing 90 common Lncrnas were used to screen lncrna expression levels in PBMC from a discovery population of patients with MS. Data from discovery and replications cohorts showed a generalized dysregulation of lncrna levels in MS patients compared with controls. MALAT1, MEG9, NRON, ANRIL, TUG1, XIST, SOX2OT, GOMAFU, HULC, BACE-1AS were significantly downregulated in MS patients in comparison with controls. Therefore, we performed a validation analysis in an independent cohort of Belgian origin. In this study, NRON and TUG1 downregulations in MS patients compared with controls were confirmed (p <= .05 and p <= .0001 respectively), whereas considering the other lncrnas, the statistical threshold was not reached. Lncrnas profiling could thus represent a new challenge in the research of easy detectable biomarkers of disease susceptibility and progression.

关键词： Multiple Sclerosis non coding rna Gene expression Biomarker

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