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CURATOR

I am a scientist specialized in mitochondria and genetics, but above all, I am just curious guy who loves learning new things.

PINBOARD SUMMARY

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.

12 ITEMS PINNED

Emerging role of miRNA in attention deficit hyperactivity disorder: a systematic review.

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

Tuning of major signaling networks (TGF-β, Wnt, Notch and Hedgehog) by miRNAs in human stem cells commitment to different lineages: Possible clinical application.

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

Genetic and epigenetic alterations in meningiomas.

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