miR-146 is a family of
microRNA precursors found in
mammals, including
humans. The ~22
nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme
Dicer.[1] This sequence then associates with
RISC which effects
RNA interference.[2]
miR-146 is primarily involved in the regulation of
inflammation[3] and other process that function in the
innate immune system.[4] Loss of functional miR-146 (and
mir-145) could predispose an individual to suffer from
chromosome 5q deletion syndrome.[5] miR-146 has also been reported to be highly upregulated in
osteoarthritis cartilage, and could be involved in its
pathogenesis.[6] mir-146 expression is associated with survival in triple negative breast cancer.[7]
Function
miR-146 is thought to be a mediator of inflammation along with another microRNA,
mir-155. The expression of miR-146 is upregulated by inflammatory factors such as
interleukin 1 and
tumor necrosis factor-alpha.[8] miR-146 dysregulates a number of targets which are mostly involved in
toll-like receptor pathways that bring about a
cytokine response as part of the innate immune system.[4][8] miR-146 operates in a feedback system or "negative regulatory loop"[9] to finely tune inflammatory responses.[5]
Applications
miR-146 could be used as a
biomarker for
sepsis.[10] 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.[11] miR-146a could be targeted therapeutically as its depletion has implication in the hyperactive response to infection.[12]
^
abSonkoly E, Ståhle M, Pivarcsi A (Apr 2008). "MicroRNAs and immunity: novel players in the regulation of normal immune function and inflammation". Seminars in Cancer Biology. 18 (2): 131–40.
doi:
10.1016/j.semcancer.2008.01.005.
PMID18291670.
^Lánczky A, Nagy Á, Bottai G, Munkácsy G, Szabó A, Santarpia L, Győrffy B (2016-12-01). "miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients". Breast Cancer Research and Treatment. 160 (3): 439–446.
doi:
10.1007/s10549-016-4013-7.
ISSN1573-7217.
PMID27744485.
S2CID11165696.
^
abSheedy FJ, O'Neill LA (Dec 2008). "Adding fuel to fire: microRNAs as a new class of mediators of inflammation". Annals of the Rheumatic Diseases. 67 (Suppl 3): iii50-5.
doi:
10.1136/ard.2008.100289.
PMID19022814.
S2CID20802154.
^Gîză DE, Vasilescu C (Sep–Oct 2010). "[MicroRNA's role in sepsis and endotoxin tolerance. More players on the stage]". Chirurgia (Bucur.). 105 (5): 625–30.
PMID21141085.
Jädersten M, Hellström-Lindberg E (May 2010). "New clues to the molecular pathogenesis of myelodysplastic syndromes". Experimental Cell Research. 316 (8): 1390–6.
doi:
10.1016/j.yexcr.2010.02.043.
PMID20211165.