I am a scientist specialized in mitochondria and genetics, but above all, I am just curious guy who loves learning new things.
Big power comes in small sizes...
In 10 seconds? All of our cells carry exactly the same DNA, but it is expressed differently depending on the type of cell, the developmental stage and physiological changes. Imagine it like a huge control board with little fingers turning the buttons on or off depending on what is needed. And the smallest of those fingers are microRNAs.
What are microRNAs? These are small non-coding RNAs that target mRNAs to inhibit their translation, thereby turning off the expression of a specific gene, and they have been established as key players in the molecular mechanisms that allow cell differentiation, the maintenance of normal homeostasis and the regulation of disease pathogenesis.
And what mechanisms do microRNAs control? MicroRNAs are involved in virtually every biological function, like MotomiRs, specifically required for motor neuron development and function, or GeromiRs, which modulate lifespan and are implicated in aging. Others are involved in organ injury and repair, stem cell reprograming, spermatogenesis or placental development during pregnancy.
So their dysregulation could cause any sort of disease? Indeed, although research on microRNAs is recent it has already been established that their dysregulation can have negative consequences on health, for example in the development of psychiatric conditions such as depression, bipolar disorder, schizophrenia, autism or ADHD.
The good part is that microRNAs will certainly have a huge impact on treating disease because they are easy to measure, making them very good biomarkers to detect disease, and the use of artificial miRNAs could be an effective therapeutic strategy to modify gene expression and treat several pathologies.
Abstract: MicroRNAs (miRNAs) are a group of small noncoding RNA molecules, 18–25 nucleotides in length, which can negatively regulate gene expression at the post-transcriptional level by binding to messenger RNAs. About half of all identified miRNAs in humans are expressed in the brain and display regulatory functions important for many biological processes related to the development of the central nervous system (CNS). Disruptions in miRNA biogenesis and miRNA-target interaction have been related to CNS diseases, including psychiatric disorders. In this review, we focus on the role of miRNAs in autism spectrum disorder (ASD) and summarize recent findings about ASD-associated genetic variants in miRNA genes, in miRNA biogenesis genes, and miRNA targets. We discuss deregulation of miRNA expression in ASD and functional validation of ASD-related miRNAs in animal models. Including miRNAs in studies of ASD will contribute to our understanding of its etiology and pathogenesis and facilitate the discrimination between different disease subgroups. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Pub.: 17 Apr '17, Pinned: 23 Jun '17
Abstract: MicroRNAs (miRNAs) are endogenous approximately 23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
Pub.: 27 Jan '09, Pinned: 23 Jun '17
Abstract: This review focuses on the recent emergence of microRNAs (miRNAs) as metabolic and developmental regulators in pregnancy and their role in the development of gestational diabetes mellitus (GDM). MiRNAs are short and stable RNA sequences that repress protein synthesis through interference with messenger RNA translation.The placenta produces numerous miRNAs with some of them being released in the maternal circulation. These miRNA genes are encoded into specific clusters and expressed preferentially by placental cells, in a time-dependent manner. They were shown to be dysregulated in plasma and placenta from women suffering from GDM and associated with pregnancy and birth-related outcomes. The discovery of pregnancy-related miRNAs and their respective characterization will provide us with important information as to their function in maternal and placental metabolic regulation. More studies are needed to determine whether they will be useful for early screening of GDM.
Pub.: 06 Apr '17, Pinned: 23 Jun '17
Abstract: Mammalian spermatogenesis contains three continuous and organized processes, by which spermatogonia undergo mitosis and differentiate to spermatocytes, follow on meiosis to form haploid spermatids and ultimately transform into spermatozoa. These processes require an accurately, spatially and temporally regulated gene expression patterns. The microRNAs are a novel class of post-transcriptional regulators. Cumulating evidences have demonstrated that microRNAs are expressed in a cell-specific or stage-specific manner during spermatogenesis. In this review, we focus on the roles of microRNAs in spermatogenesis. We highlight that N6-methyladenosine (m6A) is involved in the biogenesis of microRNAs and miRNA regulates the m6A modification on mRNA, and that specific miRNAs have been exploited as potential biomarkers for the male factor infertility, which will provide insightful understanding of microRNA roles in spermatogenesis.
Pub.: 05 May '17, Pinned: 23 Jun '17
Abstract: Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric disorder whose aetiology still remains elusive. Nevertheless, evidence supports a high genetic contribution that interacts with environmental factors, also known to modulate epigenetic processes. These epigenetic modulators are a class of non-coding RNAs, microRNAs (miRNAs), known as post-transcriptional regulators, which have emerged as prospective players in neuropsychiatric disorders since they play a role in brain development, synapse formation, and the fine-tuning of genes underlying synaptic and memory formation. Here, we review the current literature following a systematic search up until August 2016. The keywords used were "ADHD", "attention deficit hyperactivity disorder", "attention hyperactivity" in combination with "miRNA" or "microRNA". A total of 9 studies out of 34 met inclusion criteria. The results provide preliminary information, shedding light on two important aspects. First, it depicts that miRNAs modulate expression of genes (BDNF, DAT1, HTR2C, HTR1B, SNAP-25) linked to ADHD aetiology. Dysregulation of miRNAs affects regulatory mechanisms of aforementioned genes, which may affect neurodevelopmental processes leading to alterations. Secondly, altered peripheral miRNA levels are observed in both ADHD animal model and humans, suggesting a notion of utilizing circulatory miRNA in disease diagnosis. Therefore, deciphering the role of miRNAs in ADHD seems a promising step in understanding its aetiology.
Pub.: 12 May '17, Pinned: 23 Jun '17
Abstract: Stem cells are undifferentiated cells and have multi-lineage differentiation potential. Generally, stem cells are classified into adult stem cells, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Stem cells have great potential in clinical therapy due to their pluripotency and self-renewal ability. microRNAs (miRNAs) are small non-coding RNAs which are evolutionarily conserved and participate in the pathogenesis of many diseases, cell cycle regulation, apoptosis, aging, cell fate decisions, and different signaling pathways. Different kinds of stem cells possess distinct miRNA expression profiles. Our review summarizes the critical roles of miRNAs in stem cell reprogramming, pluripotency maintenance, and differentiation. In the future, miRNAs may greatly contribute to stem cell clinical therapy and have potential applications in regenerative medicine.
Pub.: 13 May '17, Pinned: 23 Jun '17
Abstract: Two distinguishing characteristics of stem cells, their continuous division in the undifferentiated state and growth into any cell types, are orchestrated by a number of cell signaling pathways. These pathways act as a niche factor in controlling variety of stem cells. The core stem cell signaling pathways include Wingless-type (Wnt), Hedgehog (HH), and Notch. Additionally, they critically regulate the self-renewal and survival of cancer stem cells. Conversely, stem cells' main properties, lineage commitment and stemness, are tightly controlled by epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNA-mediated regulatory events. MicroRNAs (miRNAs) are cellular switches that modulate stem cells outcomes in response to diverse extracellular signals. Numerous scientific evidences implicating miRNAs in major signal transduction pathways highlight new crosstalks of cellular processes. Aberrant signaling pathways and miRNAs levels result in developmental defects and diverse human pathologies. This review discusses the crosstalk between the components of main signaling networks and the miRNA machinery, which plays a role in the context of stem cells development and provides a set of examples to illustrate the extensive relevance of potential novel therapeutic targets.
Pub.: 16 May '17, Pinned: 23 Jun '17
Abstract: Organ damage and resulting pathologies often involve multiple deregulated pathways. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate a multitude of genes at the post-transcriptional level. Since their discovery over two decades ago, miRNAs have been established as key players in the molecular mechanisms of mammalian biology including the maintenance of normal homeostasis and the regulation of disease pathogenesis. In recent years, there has been substantial progress in innovative techniques to measure miRNAs along with advances in targeted delivery of agents modulating their expression. This has expanded the scope of miRNAs from being important mediators of cell signaling to becoming viable quantitative biomarkers and therapeutic targets. Currently, miRNA therapeutics are in clinical trials for multiple disease areas and vast numbers of patents have been filed for miRNAs involved in various pathological states. In this review, we summarize miRNAs involved in organ injury and repair, specifically with regard to organs that are the most susceptible to injury: the liver, heart and kidney. In addition, we review the current state of knowledge on miRNA biology, miRNA biomarkers and nucleotide-based therapeutics designed to target miRNAs to prevent organ injury and promote repair.
Pub.: 16 May '17, Pinned: 23 Jun '17
Abstract: Ageing is a complex biological process characterized by the progressive loss of biological fitness due to the accumulation of macromolecular and cellular damage that affects most living organisms. Moreover, ageing is an important risk factor for many pathologies, including cardiovascular diseases, neurological disorders, and cancer. However, the ageing rate can be modulated by genetic, nutritional, and pharmacological factors, highlighting the concept of "ageing plasticity". Progeroid syndromes are a group of rare genetic diseases that resemble many characteristics of physiological ageing. Accordingly, studies on these diseases have been very useful for gaining mechanistic insights in ageing biology. In recent years, a great effort has been made in ageing research and several works have confirmed that geromiRs, the growing subgroup of miRNAs implicated in ageing, are able to modulate organismal lifespan. However, very little is still known about the impact of miRNA in premature ageing. In this review, we will address the functional relevance of this class of small non-coding RNAs in the regulation of the hallmarks of progeroid syndromes. In addition, we will discuss the potential strategies for managing progeria based on geromiR modulation.
Pub.: 16 May '17, Pinned: 23 Jun '17
Abstract: Parkinson's disease is the second most common neurodegenerative disease commonly affecting the older population. Loss of dopaminergic neurons in the substantia nigra of brain leads to impairment of motor activities as well as cognitive defects. There are many underlying causes to this disease, both genetic and epigenetic, which are yet to be fully explored. Non-coding RNAs are significant part of our genome and are involved in various cellular processes. MicroRNAs, which are small non-coding RNAs having 20-22 nucleotides, are involved in many underlying mechanisms of pathogenesis of several neurodegenerative diseases including Parkinson's. This review focuses on the role played by microRNAs in regulating various genes responsible for the onset and pathogenesis of Parkinson's disease and various literature evidences pointing at the usefulness of targeting specific microRNAs as a potential alternate therapeutic strategy for successful impairment of the disease progression. This review also discusses about various biofluid-based microRNA markers which may be potentially utilized for diagnostic purposes.
Pub.: 21 May '17, Pinned: 23 Jun '17
Abstract: Meningiomas originate from the arachnoid layer of the meninges and divided histologically into three grades: benign (grade I), atypical (grade II), and malignant meningiomas (grade III). Genetic alterations in grade I meningiomas include frequent deletions of chromosomal locus 22q12 and NF2 gene mutations and uncommon somatic SMARCB1 and SMARCE1gene mutations; In grade II meningiomas, chromosomal losses occur on 1p, 22q, 14q, 18q, 10, and 6q, and gains on 20q, 12q, 15q, 1q, 9q, and 17q; In grade III meningiomas, losses have been recognized on 6q, 10, and 14q and alterations of PTEN, CDKN2A and CDKN2B genes. Epigenetic alterations in meningiomas include hypermethylation of the tumor suppressor genes p73 in grade I meningiomas and TIMP3 GSTP1, MEG3, HOXA6, HOXA9, PENK, WNK2 and UPK3A genes with an increasing frequency according to grade. Abnormal expression of IGF signaling family genes and Wnt signaling pathway is associated with meningioma progression. MiRNA expression profiling of meningiomas show downregulation of miR-29c-3p, miR-200a, miR-145 and miR- 219-5p and upregulation of miR-21 miR-335 and miR-190a levels. In conclusion, extensive genetic and epigenetic alterations exist in meningiomas that may help assessing prognosis. In addition, since miRNA expression may be modified by artificial miRNAs, new effective therapeutic strategies may be developed especially for resistant or high grade meningiomas.
Pub.: 22 May '17, Pinned: 23 Jun '17
Abstract: Advances in genomics technology over recent years have led to the surprising discovery that the genome is far more pervasively transcribed than was previously appreciated. Much of the newly-discovered transcriptome appears to represent long non-coding RNA (lncRNA), a heterogeneous group of largely uncharacterised transcripts. Understanding the biological function of these molecules represents a major challenge and in this review we discuss some of the progress made to date. One major theme of lncRNA biology seems to be the existence of a network of interactions with microRNA (miRNA) pathways. lncRNA has been shown to act as both a source and an inhibitory regulator of miRNA. At the transcriptional level, a model is emerging whereby lncRNA bridges DNA and protein by binding to chromatin and serving as a scaffold for modifying protein complexes. Such a mechanism can bridge promoters to enhancers or enhancer-like non-coding genes by regulating chromatin looping, as well as conferring specificity on histone modifying complexes by directing them to specific loci.
Pub.: 23 May '17, Pinned: 23 Jun '17