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miR-146 is a family of
microRNA precursors found in
mammal
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
s, including
human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
s. The ~22
nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
mature miRNA sequence is excised from the precursor hairpin by the enzyme
Dicer. This sequence then associates with
RISC
In computer engineering, a reduced instruction set computer (RISC) is a computer designed to simplify the individual instructions given to the computer to accomplish tasks. Compared to the instructions given to a complex instruction set comput ...
which effects
RNA interference.
miR-146 is primarily involved in the regulation of
inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
and other process that function in the
innate immune system
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...
.
Loss of functional miR-146 (and
mir-145
In molecular biology, mir-145 microRNA is a short RNA molecule that in humans is encoded by the MIR145 gene. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.
Targets
MicroRNAs are involved in down-reg ...
) could predispose an individual to suffer from
chromosome 5q deletion syndrome
Chromosome 5q deletion syndrome is an acquired, hematological disorder characterized by loss of part of the long arm (q arm, band 5q33.1) of human chromosome 5 in bone marrow myelocyte cells. This chromosome abnormality is most commonly associate ...
.
miR-146 has also been reported to be highly upregulated in
osteoarthritis
Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...
cartilage, and could be involved in its
pathogenesis. mir-146 expression is associated with survival in triple negative breast cancer.
Function
miR-146 is thought to be a mediator of inflammation along with another microRNA,
mir-155
MiR-155 is a microRNA that in humans is encoded by the ''MIR155'' host gene or ''MIR155HG''. MiR-155 plays a role in various physiological and pathological processes. Exogenous molecular control ''in vivo'' of miR-155 expression may inhibit mali ...
. The expression of miR-146 is upregulated by inflammatory factors such as
interleukin 1 and
tumor necrosis factor-alpha.
miR-146 dysregulates a number of targets which are mostly involved in
toll-like receptor
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are Bitopic protein, single-pass membrane-spanning Receptor (biochemistry), receptors usually expressed on sentinel cells such as macrophage ...
pathways that bring about a
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
response as part of the innate immune system.
miR-146 operates in a feedback system or "negative regulatory loop" to finely tune inflammatory responses.
Applications
miR-146 could be used as a
biomarker for
sepsis
Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
. In addition it was found to be absent from the exosomes of prion infected cells suggesting it could be used as a biomarker for prion infection. miR-146a could be targeted therapeutically as its depletion has implication in the hyperactive response to infection.
References
Further reading
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See also
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microRNA (
miRNA)
External links
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{{miRNA precursor families
MicroRNA