Oestrogen-dependent regulation of miRNA biogenesis: many ways to skin the cat

2012 ◽  
Vol 40 (4) ◽  
pp. 752-758 ◽  
Author(s):  
Ananya Gupta ◽  
Emer Caffrey ◽  
Grace Callagy ◽  
Sanjeev Gupta
Keyword(s):  
Untranslated Region ◽  
Steroid Hormone ◽  
Mirna Biogenesis ◽  
Transcriptional Level ◽  
Normal Female ◽  
Cellular Processes ◽  
Non Coding Rnas ◽  
Multiple Levels ◽  
Oestrogen Signalling ◽  
Er Status

The steroid hormone oestrogen is central to normal female physiology, reproduction and behaviour, through its effects on cellular processes including cell proliferation and cell survival. The effects of oestrogen are mediated by nuclear ERs (oestrogen receptors). ER status is important for the development, progression and treatment of breast cancer. miRNAs (microRNAs) are small non-coding RNAs that bind the 3′-UTR (untranslated region) of target mRNAs to reduce their stability and/or translation. miRNAs participate in oestrogen signalling by regulating oestrogen-responsive genes and pathways. Interestingly expression and maturation of miRNAs can also be regulated by ER signalling at multiple levels. In addition to regulating the expression of miRNAs at the transcriptional level, ER appears to be able to regulate the biogenesis of miRNAs. In the present review, we summarize recent findings on miRNA biogenesis and describe various mechanisms by which oestrogen signalling can modulate the production of miRNAs.

Using miRNAs as diagnostic biomarkers for male infertility: opportunities and challenges

2020 ◽  
Vol 26 (4) ◽  
pp. 199-214 ◽  
Author(s):  
A Vashisht ◽  
G K Gahlay
Keyword(s):  
Male Infertility ◽  
Human Development ◽  
Infertility Treatment ◽  
Mirna Biogenesis ◽  
Testicular Development ◽  
Transcriptional Level ◽  
Diagnostic Biomarkers ◽  
Clinical Disorder ◽  
Epididymal Maturation ◽  
Non Coding Rnas

Abstract The non-coding genome has been extensively studied for its role in human development and diseases. MicroRNAs (miRNAs) are small non-coding RNAs, which can regulate the expression of hundreds of genes at the post-transcriptional level. Therefore, any defects in miRNA biogenesis or processing can affect the genes and have been linked to several diseases. Male infertility is a clinical disorder with a significant number of cases being idiopathic. Problems in spermatogenesis and epididymal maturation, testicular development, sperm maturation or migration contribute to male infertility, and many of these idiopathic cases are related to issues with the miRNAs which tightly regulate these processes. This review summarizes the recent research on various such miRNAs and puts together the candidate miRNAs that may be used as biomarkers for diagnosis. The development of strategies for male infertility treatment using anti-miRs or miRNA mimics is also discussed. Although promising, the development of miRNA diagnostics and therapeutics is challenging, and ways to overcome some of these challenges are also reviewed.

scholarly journals MicroRNAs and endocrine biology

2005 ◽  
Vol 187 (3) ◽  
pp. 327-332 ◽  
Author(s):  
Trinna L Cuellar ◽  
Michael T McManus
Keyword(s):  
Adipocyte Differentiation ◽  
Current Knowledge ◽  
B Cell Development ◽  
Endocrine Function ◽  
Mirna Biogenesis ◽  
Transcriptional Level ◽  
Biological Processes ◽  
Regulate Gene Expression ◽  
Non Coding Rnas ◽  
Regulate Gene

microRNAs (miRNAs) are highly conserved, non-coding RNAs that powerfully regulate gene expression at the post-transcriptional level. These fascinating molecules play essential roles in many biological processes in mammals, including insulin secretion, B-cell development, and adipocyte differentiation. This review provides a general background regarding current knowledge about miRNA biogenesis and the potential contributions of these RNAs to endocrine function.

scholarly journals Complexity in regulating microRNA biogenesis in cancer

2020 ◽  
Vol 245 (5) ◽  
pp. 395-401
Author(s):  
Pai-Sheng Chen ◽  
Shao-Chieh Lin ◽  
Shaw-Jenq Tsai
Keyword(s):  
Noncoding Rna ◽  
Target Genes ◽  
Mirna Biogenesis ◽  
Transcriptional Level ◽  
Cellular Processes ◽  
Wide Range ◽  
Mirnas Expression ◽  
Cellular Phenotypes ◽  
Fine Tune ◽  
Processing Factors

The discovery of microRNA (miRNA) significantly extends our knowledge on gene regulation and noncoding gene functions. MiRNAs are important post-transcriptional regulators involve in a wide range of biological functions and diseases, including cancer. MiRNAs are produced by a unique biogenesis pathway involving the two-step sequential nuclear and cytoplasmic RNase-dependent processing at post-transcriptional level. However, a specific (set) of miRNA(s) is (are) synthesized under certain circumstance or developmental/pathological stage to fine-tune the gene expression profile. In this minireview, we will discuss the mechanism of miRNA biogenesis in cancer, mainly focusing on how Drosha and Dicer, two critical molecules controlling miRNA biogenesis, are modulated and which factor contributes to the specificity of selected miRNA maturation. Impact statement The canonical maturation pathway of miRNAs is highly conserved, indicating the crucial roles of these mini-regulators in most cellular processes. Dysregulation of specific miRNAs or imbalance of miRNA abundance has been observed in cancers. Accumulating evidence has shown that the interplay between miRNA processing factors and regulatory proteins previously known as key players in cancer malignancy regulates the biogenesis of miRNAs, expression of target genes, and eventually the alteration of cellular phenotypes. This minireview summarizes the current findings in the modulation of miRNA biogenesis in cancer to advance the understanding of how noncoding RNA contributes to cancer development and malignancy.

scholarly journals Potential miRNAs for miRNA-Based Therapeutics in Breast Cancer

2020 ◽  
Vol 6 (3) ◽  
pp. 29
Author(s):  
Jun Sheng Wong ◽  
Yoke Kqueen Cheah
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Cancer Recurrence ◽  
Mirna Biogenesis ◽  
In Vivo Models ◽  
Cellular Processes ◽  
Non Coding Rnas ◽  
Tumor Suppressor Mirnas

MicroRNAs (miRNAs) are small non-coding RNAs that can post-transcriptionally regulate the genes involved in critical cellular processes. The aberrant expressions of oncogenic or tumor suppressor miRNAs have been associated with cancer progression and malignancies. This resulted in the dysregulation of signaling pathways involved in cell proliferation, apoptosis and survival, metastasis, cancer recurrence and chemoresistance. In this review, we will first (i) provide an overview of the miRNA biogenesis pathways, and in vitro and in vivo models for research, (ii) summarize the most recent findings on the roles of microRNAs (miRNAs) that could potentially be used for miRNA-based therapy in the treatment of breast cancer and (iii) discuss the various therapeutic applications.

scholarly journals Deciphering miRNAs’ Action through miRNA Editing

2019 ◽  
Vol 20 (24) ◽  
pp. 6249 ◽  
Author(s):  
Marta Correia de Sousa ◽  
Monika Gjorgjieva ◽  
Dobrochna Dolicka ◽  
Cyril Sobolewski ◽  
Michelangelo Foti
Keyword(s):  
Stress Responses ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Metabolic Diseases ◽  
Rna Binding Proteins ◽  
Mrna Translation ◽  
Mirna Biogenesis ◽  
Transcriptional Level ◽  
Non Coding Rnas ◽  
Mirna Editing

MicroRNAs (miRNAs) are small non-coding RNAs with the capability of modulating gene expression at the post-transcriptional level either by inhibiting messenger RNA (mRNA) translation or by promoting mRNA degradation. The outcome of a myriad of physiological processes and pathologies, including cancer, cardiovascular and metabolic diseases, relies highly on miRNAs. However, deciphering the precise roles of specific miRNAs in these pathophysiological contexts is challenging due to the high levels of complexity of their actions. Indeed, regulation of mRNA expression by miRNAs is frequently cell/organ specific; highly dependent on the stress and metabolic status of the organism; and often poorly correlated with miRNA expression levels. Such biological features of miRNAs suggest that various regulatory mechanisms control not only their expression, but also their activity and/or bioavailability. Several mechanisms have been described to modulate miRNA action, including genetic polymorphisms, methylation of miRNA promoters, asymmetric miRNA strand selection, interactions with RNA-binding proteins (RBPs) or other coding/non-coding RNAs. Moreover, nucleotide modifications (A-to-I or C-to-U) within the miRNA sequences at different stages of their maturation are also critical for their functionality. This regulatory mechanism called “RNA editing” involves specific enzymes of the adenosine/cytidine deaminase family, which trigger single nucleotide changes in primary miRNAs. These nucleotide modifications greatly influence a miRNA’s stability, maturation and activity by changing its specificity towards target mRNAs. Understanding how editing events impact miRNA’s ability to regulate stress responses in cells and organs, or the development of specific pathologies, e.g., metabolic diseases or cancer, should not only deepen our knowledge of molecular mechanisms underlying complex diseases, but can also facilitate the design of new therapeutic approaches based on miRNA targeting. Herein, we will discuss the current knowledge on miRNA editing and how this mechanism regulates miRNA biogenesis and activity.

scholarly journals The discovery potential of RNA processing profiles

2016 ◽  
Author(s):  
Amadís Pagès ◽  
Ivan Dotu ◽  
Joan Pallarès-Albanell ◽  
Eulàlia Martí ◽  
Roderic Guigó ◽  
...  
Keyword(s):  
Clustering Algorithms ◽  
Computational Method ◽  
Mirna Biogenesis ◽  
Cellular Processes ◽  
Cell Compartments ◽  
Non Coding Rna ◽  
Density Based Clustering ◽  
Discovery Potential ◽  
Non Coding Rnas ◽  
Dynamic Time

AbstractSmall non-coding RNAs are highly abundant molecules that regulate essential cellular processes and are classified according to sequence and structure. Here we argue that read profiles from size-selected RNA sequencing capture the post-transcriptional processing specific to each RNA family, thereby providing functional information independently of sequence and structure. We developed SeRPeNT, the first unsupervised computational method that exploits reproducibility across replicates and uses dynamic time-warping and density-based clustering algorithms to identify, characterize and compare small non-coding RNAs (sncRNAs) by harnessing the power of read profiles. We applied SeRPeNT to: a) generate an extended human annotation with 671 new sncRNAs from known classes and 131 from new potential classes, b) show pervasive differential processing between cell compartments and c) predict new molecules with miRNA-like behaviour from snoRNA, tRNA and long non-coding RNA precursors, potentially dependent on the miRNA biogenesis pathway. Furthermore, we validated experimentally four predicted novel non-coding RNAs: a miRNA, a snoRNA-derived miRNA, a processed tRNA and a new uncharacterized sncRNA. SeRPeNT facilitates fast and accurate discovery and characterization of small non-coding RNAs at unprecedented scale. SeRPeNT code is available under the MIT license at https://github.com/comprna/SeRPeNT.

scholarly journals ROLE OF COMPONENTS OF microRNA MACHINERY IN CARCINOGENESIS

2018 ◽  
Vol 40 (1) ◽  
pp. 2-9 ◽  
Author(s):  
R Kian ◽  
S Moradi ◽  
S Ghorbian
Keyword(s):  
Broad Class ◽  
Mirna Biogenesis ◽  
Basic Principles ◽  
Cellular Processes ◽  
Posttranscriptional Gene Regulation ◽  
Non Coding Rnas ◽  
Major Factors ◽  
Eukaryotic Organisms ◽  
Tumor Types

MicroRNAs (miRNAs) are a broad class of non-coding RNAs nearly 21 nucleotides length, which play crucial functions in posttranscriptional gene regulation. These molecules are associated with many developmental and cellular processes in eukaryotic organisms. Current investigation has reported major factors contributing to miRNA biogenesis and has constituted basic principles of miRNA function. More recently, it was confirmed that various miRNAs are clearly implicated in human malignancies, such as lung, breast, ovarian, bladder, colon cancer and other kinds of carcinoma. In addition, dysregulation in the miRNA machinery elements such as Dicer, Drosha, DGCR8, Argonaut, and TRBP could be involved in the progress of many tumor types. The purpose of the current review was to compile growing information besides how miRNA biogenesis and gene silencing are modified to develop cancer.

scholarly journals Upregulation of 15 Antisense Long Non-Coding RNAs in Osteosarcoma

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1132
Author(s):  
Emel Rothzerg ◽  
Xuan Dung Ho ◽  
Jiake Xu ◽  
David Wood ◽  
Aare Märtson ◽  
...  
Keyword(s):  
Tumour Progression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Osteosarcoma Cell ◽  
Osteoblast Cell Line ◽  
Antisense Lncrnas ◽  
Non Coding Rnas ◽  
Polymerase Chain ◽  
Multiple Levels

The human genome encodes thousands of natural antisense long noncoding RNAs (lncRNAs); they play the essential role in regulation of gene expression at multiple levels, including replication, transcription and translation. Dysregulation of antisense lncRNAs plays indispensable roles in numerous biological progress, such as tumour progression, metastasis and resistance to therapeutic agents. To date, there have been several studies analysing antisense lncRNAs expression profiles in cancer, but not enough to highlight the complexity of the disease. In this study, we investigated the expression patterns of antisense lncRNAs from osteosarcoma and healthy bone samples (24 tumour-16 bone samples) using RNA sequencing. We identified 15 antisense lncRNAs (RUSC1-AS1, TBX2-AS1, PTOV1-AS1, UBE2D3-AS1, ERCC8-AS1, ZMIZ1-AS1, RNF144A-AS1, RDH10-AS1, TRG-AS1, GSN-AS1, HMGA2-AS1, ZNF528-AS1, OTUD6B-AS1, COX10-AS1 and SLC16A1-AS1) that were upregulated in tumour samples compared to bone sample controls. Further, we performed real-time polymerase chain reaction (RT-qPCR) to validate the expressions of the antisense lncRNAs in 8 different osteosarcoma cell lines (SaOS-2, G-292, HOS, U2-OS, 143B, SJSA-1, MG-63, and MNNG/HOS) compared to hFOB (human osteoblast cell line). These differentially expressed IncRNAs can be considered biomarkers and potential therapeutic targets for osteosarcoma.

scholarly journals MicroRNA expression profile in bovine mammary gland parenchyma infected by coagulase-positive or coagulase-negative staphylococci

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Emilia Bagnicka ◽  
Ewelina Kawecka-Grochocka ◽  
Klaudia Pawlina-Tyszko ◽  
Magdalena Zalewska ◽  
Aleksandra Kapusta ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Immune System ◽  
Differentially Expressed ◽  
Bacterial Invasion ◽  
Coagulase Negative Staphylococci ◽  
Cellular Processes ◽  
Differentially Expressed Mirnas ◽  
Non Coding Rnas ◽  
Coagulase Positive Staphylococci ◽  
Generation Sequencing

AbstractMicroRNAs (miRNAs) are short, non-coding RNAs, 21–23 nucleotides in length which are known to regulate biological processes that greatly impact immune system activity. The aim of the study was to compare the miRNA expression in non-infected (H) mammary gland parenchyma samples with that of glands infected with coagulase-positive staphylococci (CoPS) or coagulase-negative staphylococci (CoNS) using next-generation sequencing. The miRNA profile of the parenchyma was found to change during mastitis, with its profile depending on the type of pathogen. Comparing the CoPS and H groups, 256 known and 260 potentially new miRNAs were identified, including 32 that were differentially expressed (p ≤ 0.05), of which 27 were upregulated and 5 downregulated. Comparing the CoNS and H groups, 242 known and 171 new unique miRNAs were identified: 10 were upregulated (p ≤ 0.05), and 2 downregulated (p ≤ 0.05). In addition, comparing CoPS with H and CoNS with H, 5 Kyoto Encyclopedia of Genes and Genomes pathways were identified; in both comparisons, differentially-expressed miRNAs were associated with the bacterial invasion of epithelial cells and focal adhesion pathways. Four gene ontology terms were identified in each comparison, with 2 being common to both immune system processes and signal transduction. Our results indicate that miRNAs, especially miR-99 and miR-182, play an essential role in the epigenetic regulation of a range of cellular processes, including immunological systems bacterial growth in dendritic cells and disease pathogenesis (miR-99), DNA repair and tumor progression (miR-182).

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