miR-27 is a family of

microRNA MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...

precursors found in animals, 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. MicroRNAs are typically transcribed as ~70

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 ...

precursors and subsequently processed by the

Dicer Dicer, also known as endoribonuclease Dicer or helicase with RNase motif, is an enzyme that in humans is encoded by the gene. Being part of the RNase III family, Dicer cleaves double-stranded RNA (dsRNA) and pre-microRNA (pre-miRNA) into short d ...

enzyme to give a ~22 nucleotide product. The excised region or, mature product, of the miR-27 precursor is the microRNA mir-27. ''

Herpesvirus saimiri ''Saimiriine gammaherpesvirus 2'' (SaHV-2) is a species of virus in the genus ''Rhadinovirus'', subfamily ''Gammaherpesvirinae'', family ''Herpesviridae'', and order ''Herpesvirales''. See also * HSUR (''Herpesvirus saimiri'' U RNAs) * Squirre ...

'' expresses several non-coding RNAs (

HSUR HSURs (''Herpesvirus saimiri'' U RNAs) are viral small regulatory RNAs. They are found in ''Herpesvirus saimiri'' which is responsible for aggressive T-cell leukemias in primates. They are nuclear RNAs which bind host proteins to form small nuc ...

s) which have been found to significantly reduce the level of mir-27 in a host cell. It has been proposed that miR-27 operates together with miR-23 and mir-24 in a co-operative cluster.

Regulation of adipocyte differentiation

miR-27 is one of a number of microRNAs implicated in

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

homeostasis and

fatty acid metabolism Fatty acid metabolism consists of various metabolic processes involving or closely related to fatty acids, a family of molecules classified within the lipid macronutrient category. These processes can mainly be divided into (1) catabolic processes ...

. The miR-27 gene family has been shown to be downregulated during the differentiation of adipocytes. miR-27 inhibits adipocyte formation when overexpressed, acting by blocking the expression of two main regulators of

adipogenesis Adipogenesis is the formation of adipocytes (fat cells) from stem cells. It involves 2 phases, determination, and terminal differentiation. Determination is mesenchymal stem cells committing to the adipocyte precursor cells, also known as preadipocy ...

. MicroRNAs miR-27a and -27b have been found to negatively regulate adipocyte differentiation through regulation of the peroxisome proliferator-activated receptor gamma (PPARγ) post-transcriptionally, as well as C/EBP alpha in the case of miR-27b. miR-27 can be identified both as an adipogenic inhibitor and as playing an important role in the development of obesity.

Wnt signalling pathway

miR-27 is an activator of the

Wnt signalling pathway The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling p ...

, affecting the differentiation of mesenchymal stem cells into osteoblasts. miR-27 has been found to target and inhibit gene expression of the adenomatous polyposis coli (APC) protein, enabling it to regulate osteoblast differentiation. Expression levels of miR-27 are positively correlated with

beta-catenin Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene. Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcripti ...

, a key protein in Wnt signalling. There is activation of Wnt signalling through nuclear accumulation of this protein, which is in response to inhibition of the beta-catenin destruction complex. This in turn is brought about by APC inhibition of miR-27.

Cancer Regulation

miR-27 is known to regulate components involved in numerous types of cancer, including

breast The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues. In females, it serves as the mammary gland, which produces and secret ...

and

ovarian The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...

. miR-27a has been identified as an oncogenic microRNA and, specifically, is highly expressed in breast cancer cells. mir-27b expression is associated with survival in triple negative breast cancer patients. Inhibition of miR-27 by antisense molecules decreases cell proliferation. Antisense RNA directed against miR-27a has been shown to decrease the percentage of cells in S phase whilst also increasing those in the G2-M phase. The FOXO (Forkhead Box O) gene sub-family encodes tumour-suppressive transcription factors that regulate multiple aspects of cell cycle progression and survival. FOXO1 protein expression is down-regulated in breast tumour tissue samples; miR-27a has been identified as one of three miRNAS (along with miR-96 and miR-182) which directly target FOXO1 and regulate its endogenous expression. Suppression of miR-27a results in a FOXO1 protein increase and a consequent cell number decrease.

References

External links

* {{miRNA precursor families MicroRNA