MiR-27

Last updated
miR-27
Mir-27 SS.png
Conserved secondary structure of miR-27 prescursor
Identifiers
SymbolmiR-27
Rfam RF00644
miRBase MI0000085
miRBase family MIPF0000036
NCBI Gene 407018
HGNC 31613
Other data
RNA typemiRNA
Domain(s) Animalia
Locus Chr. 19
PDB structures PDBe

miR-27 is a family of microRNA precursors found in animals, including humans. [1] MicroRNAs are typically transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. [2] The excised region or, mature product, of the miR-27 precursor is the microRNA mir-27.

Contents

Herpesvirus saimiri expresses several non-coding RNAs (HSURs) which have been found to significantly reduce the level of mir-27 in a host cell. [3] It has been proposed that miR-27 operates together with miR-23 and mir-24 in a co-operative cluster. [4]

Regulation of adipocyte differentiation

miR-27 is one of a number of microRNAs implicated in cholesterol homeostasis and fatty acid metabolism. [5] 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. [6] 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. [7] miR-27 can be identified both as an adipogenic inhibitor and as playing an important role in the development of obesity. [6]

Wnt signalling pathway

miR-27 is an activator of the Wnt signalling pathway, affecting the differentiation of mesenchymal stem cells into osteoblasts. [8] 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, [9] 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. [9]

Cancer Regulation

miR-27 is known to regulate components involved in numerous types of cancer, including breast [10] [11] and ovarian. [12] 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. [13] Inhibition of miR-27 by antisense molecules decreases cell proliferation. [14] 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. [15]

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. [15]

Related Research Articles

<span class="mw-page-title-main">Osteoprotegerin</span> Mammalian protein found in Homo sapiens

Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor (OCIF) or tumour necrosis factor receptor superfamily member 11B (TNFRSF11B), is a cytokine receptor of the tumour necrosis factor (TNF) receptor superfamily encoded by the TNFRSF11B gene.

mir-9/mir-79 microRNA precursor family

The miR-9 microRNA, is a short non-coding RNA gene involved in gene regulation. The mature ~21nt miRNAs are processed from hairpin precursor sequences by the Dicer enzyme. The dominant mature miRNA sequence is processed from the 5' arm of the mir-9 precursor, and from the 3' arm of the mir-79 precursor. The mature products are thought to have regulatory roles through complementarity to mRNA. In vertebrates, miR-9 is highly expressed in the brain, and is suggested to regulate neuronal differentiation. A number of specific targets of miR-9 have been proposed, including the transcription factor REST and its partner CoREST.

mir-10 microRNA precursor family

The mir-10 microRNA precursor is a short non-coding RNA gene involved in gene regulation. It is part of an RNA gene family which contains mir-10, mir-51, mir-57, mir-99 and mir-100. mir-10, mir-99 and mir-100 have now been predicted or experimentally confirmed in a wide range of species. miR-51 and miR-57 have currently only been identified in the nematode Caenorhabditis elegans.

mir-17 microRNA precursor family

The miR-17 microRNA precursor family are a group of related small non-coding RNA genes called microRNAs that regulate gene expression. The microRNA precursor miR-17 family, includes miR-20a/b, miR-93, and miR-106a/b. With the exception of miR-93, these microRNAs are produced from several microRNA gene clusters, which apparently arose from a series of ancient evolutionary genetic duplication events, and also include members of the miR-19, and miR-25 families. These clusters are transcribed as long non-coding RNA transcripts that are processed to form ~70 nucleotide microRNA precursors, that are subsequently processed by the Dicer enzyme to give a ~22 nucleotide products. The mature microRNA products are thought to regulate expression levels of other genes through complementarity to the 3' UTR of specific target messenger RNA.

mir-92 microRNA precursor family

The miR-92 microRNAs are short single stranded non-protein coding RNA fragments initially discovered incorporated into an RNP complex with a proposed role of processing RNA molecules and further RNP assembly. Mir-92 has been mapped to the human genome as part of a larger cluster at chromosome 13q31.3, where it is 22 nucleotides in length but exists in the genome as part of a longer precursor sequence. There is an exact replica of the mir-92 precursor on the X chromosome. MicroRNAs are endogenous triggers of the RNAi pathway which involves several ribonucleic proteins (RNPs) dedicated to repressing mRNA molecules via translation inhibition and/or induction of mRNA cleavage. miRNAs are themselves matured from their long RNA precursors by ribonucleic proteins as part of a 2 step biogenesis mechanism involving RNA polymerase 2.

mir-96 microRNA

miR-96 microRNA precursor is a small non-coding RNA that regulates gene expression. microRNAs are transcribed as ~80 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~23 nucleotide products. In this case the mature sequence comes from the 5′ arm of the precursor. The mature products are thought to have regulatory roles through complementarity to mRNA.

mir-205 Micro RNA involved in the regulation of multiple genes

In molecular biology miR-205 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. They are involved in numerous cellular processes, including development, proliferation, and apoptosis. Currently, it is believed that miRNAs elicit their effect by silencing the expression of target genes.

mir-22

In molecular biology mir-22 microRNA is a short RNA molecule. MicroRNAs are an abundant class of molecules, approximately 22 nucleotides in length, which can post-transcriptionally regulate gene expression by binding to the 3' UTR of mRNAs expressed in a cell.

mir-31

miR-31 has been characterised as a tumour suppressor miRNA, with its levels varying in breast cancer cells according to the metastatic state of the tumour. From its typical abundance in healthy tissue is a moderate decrease in non-metastatic breast cancer cell lines, and levels are almost completely absent in mouse and human metastatic breast cancer cell lines. Mir-31-5p has also been observed upregulated in Zinc Deficient rats compared to normal in ESCC and in other types of cancers when using this animal model. There has also been observed a strong encapsulation of tumour cells expressing miR-31, as well as a reduced cell survival rate. miR-31's antimetastatic effects therefore make it a potential therapeutic target for breast cancer. However, these two papers were formally retracted by the authors in 2015.

mir-451 microRNA

In molecular biology mir-451 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

mir-210 microRNA

In molecular biology mir-210 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-339 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. miR-339-5p expression was associated with overall survival in breast cancer.

In molecular biology mir-340 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

Mir-423 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-489 microRNA is a short RNA molecule. MicroRNAs function is to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-153 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-186 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-764 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

<span class="mw-page-title-main">MiR-206</span>

MiR-206 is a microRNA with a sequence conserved across most mammalian species, and in humans is a member of the myo-miR family of miRNAs, which includes miR-1, miR-133, and miR-208a/b. Mir-206 is well established for the regulation of cellular processes involving skeletal muscle development, as well as mitochondrial functioning. miR-206 is studied in C2C12 myoblast cells as this is a widely used model for the study of cellular differentiation of skeletal muscle. The biogenesis of miR-206 is unique in that the primary mature transcript is generated from the 3p arm of the precursor microRNA hairpin rather than the 5p arm. Currently, miR-206 has approximately twelve miRNA family members, and the cognate seed sequence of the miR-206 family is conserved across all twelve miRNA members.

References

  1. ↑ Landgraf, P; Rusu, M; Sheridan, R; Sewer, A; Iovino, N; Aravin, A; Pfeffer, S; Rice, A; et al. (Jun 29, 2007). "A mammalian microRNA expression atlas based on small RNA library sequencing". Cell. 129 (7): 1401–14. doi:10.1016/j.cell.2007.04.040. PMC   2681231 . PMID   17604727.
  2. ↑ Ambros, V (2001). "microRNAs: tiny regulators with great potential". Cell. 107 (7): 823–826. doi: 10.1016/S0092-8674(01)00616-X . PMID   11779458. S2CID   14574186.
  3. ↑ Cazalla, D; Yario, T; Steitz, JA (Jun 18, 2010). "Down-regulation of a host microRNA by a Herpesvirus saimiri noncoding RNA". Science. 328 (5985): 1563–6. Bibcode:2010Sci...328.1563C. doi:10.1126/science.1187197. PMC   3075239 . PMID   20558719.
  4. ↑ Chhabra, R; Dubey, R; Saini, N (Sep 3, 2010). "Cooperative and individualistic functions of the microRNAs in the miR-23a~27a~24-2 cluster and its implication in human diseases". Molecular Cancer. 9: 232. doi: 10.1186/1476-4598-9-232 . PMC   2940846 . PMID   20815877.
  5. ↑ Fernández-Hernando, C; Suárez, Y; Rayner, KJ; Moore, KJ (April 2011). "MicroRNAs in lipid metabolism". Current Opinion in Lipidology. 22 (2): 86–92. doi:10.1097/MOL.0b013e3283428d9d. PMC   3096067 . PMID   21178770.
  6. 1 2 Lin Q, Gao Z, Alarcon RM, Ye J, Yun Z (2009). "A role of miR-27 in the regulation of adipogenesis". FEBS J. 276 (8): 2348–58. doi:10.1111/j.1742-4658.2009.06967.x. PMC   5330386 . PMID   19348006.
  7. ↑ Kim SY, Kim AY, Lee HW, Son YH, Lee GY, Lee JW, et al. (2010). "miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression". Biochem Biophys Res Commun. 392 (3): 323–8. doi:10.1016/j.bbrc.2010.01.012. PMID   20060380.
  8. ↑ Wang, T; Xu, Z (Nov 12, 2010). "miR-27 promotes osteoblast differentiation by modulating Wnt signaling". Biochemical and Biophysical Research Communications. 402 (2): 186–9. doi:10.1016/j.bbrc.2010.08.031. PMID   20708603.
  9. 1 2 Wang T, Xu Z (2010). "miR-27 promotes osteoblast differentiation by modulating Wnt signaling". Biochem Biophys Res Commun. 402 (2): 186–9. doi:10.1016/j.bbrc.2010.08.031. PMID   20708603.
  10. ↑ Li, X; Mertens-Talcott, SU; Zhang, S; Kim, K; Ball, J; Safe, S (June 2010). "MicroRNA-27a Indirectly Regulates Estrogen Receptor {alpha} Expression and Hormone Responsiveness in MCF-7 Breast Cancer Cells". Endocrinology. 151 (6): 2462–73. doi:10.1210/en.2009-1150. PMC   2875816 . PMID   20382698.
  11. ↑ Guttilla, IK; White, BA (Aug 28, 2009). "Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells". The Journal of Biological Chemistry. 284 (35): 23204–16. doi: 10.1074/jbc.M109.031427 . PMC   2749094 . PMID   19574223.
  12. ↑ Kontorovich, T; Levy, A; Korostishevsky, M; Nir, U; Friedman, E (Aug 1, 2010). "Single nucleotide polymorphisms in miRNA binding sites and miRNA genes as breast/ovarian cancer risk modifiers in Jewish high-risk women". International Journal of Cancer. 127 (3): 589–97. doi:10.1002/ijc.25065. PMID   19950226. S2CID   29984487.
  13. ↑ Lánczky, András; Nagy, Ádám; Bottai, Giulia; Munkácsy, Gyöngyi; Szabó, András; Santarpia, Libero; Győrffy, Balázs (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. ISSN   1573-7217. PMID   27744485. S2CID   11165696.
  14. ↑ Mertens-Talcott SU, Chintharlapalli S, Li X, Safe S (2007). "The oncogenic microRNA-27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells". Cancer Res. 67 (22): 11001–11. doi: 10.1158/0008-5472.CAN-07-2416 . PMID   18006846.
  15. 1 2 Guttilla IK, White BA (2009). "Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells". J Biol Chem. 284 (35): 23204–16. doi: 10.1074/jbc.M109.031427 . PMC   2749094 . PMID   19574223.
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