miR-27 is a family of

microRNA Micro ribonucleic acid (microRNA, miRNA, μRNA) are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcr ...

precursors found in animals, including

human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

s. MicroRNAs are typically transcribed as ~70

nucleotide Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...

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 shor ...

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) * Squirrel mo ...

'' expresses several non-coding RNAs (

HSUR HSURs (''Herpesvirus saimiri'' U RNAs) are viral small non-coding RNA, 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 f ...

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 the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

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 processe ...

. 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 lipoblast ...

. 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 In cellular biology, 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, pronounced "wint", is a portmanteau created from the ...

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

, 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 breasts are two prominences located on the upper ventral region of the torso among humans and other primates. Both sexes develop breasts from the same embryology, embryological tissues. The relative size and development of the breasts is ...

and

ovarian The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are endoc ...

. 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