Mir-126

Last updated
mir-126
MiR-126 secondary structure.png
miR-126 precursor secondary structure and sequence conservation.
Identifiers
Symbolmir-126
Rfam RF00701
miRBase family MIPF0000115
OMIM 611767
Other data
RNA type microRNA
Domain(s) Eukaryota
SO SO:0001244
PDB structures PDBe

In molecular biology mir-126 is a short non-coding RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several pre- and post-transcription mechanisms.

Contents

Mir-126 is a human microRNA that is expressed only in endothelial cells, throughout capillaries as well as larger blood vessels, [1] and acts upon various transcripts to control angiogenesis. [2]

Genomic Location

miR-126 is located within the 7th intron of the EGFL7 gene which resides on human chromosome 9. [3]

mir-126*

mir-126* is the complementary strand to mir-126 which forms once the double stranded pri-miRNA is cleaved and the two strands denature, separating. mir-126* is less abundantly found in organisms than mir-126 and fewer roles in regulating gene expression have been identified. However, mir-126* has recently been implicated in the silencing of prostien in non-endothelial cells. Prostein is able to be produced specifically in the prostate through the silencing of both mir-126* and EGFL7. [4]

Regulation of expression

mir-126 is regulated by the binding of two transcription factors: ETS1 and ETS2. [5] Binding of these factors induce the transcription of the mir-126 pre-miRNA resulting in the formation of the hairpin pri-miRNA. Hairpin miRNA is targeted to Dicer for cleavage, producing mature mir-126 and mir-126* transcripts.

Epigenetic regulation of the host gene by accumulation of methylation and gene silencing nucleosomes reduces expression of intronic miRNA affecting. This has been observed in cancers which benefit from the silencing of both EGFL7 and mir-126, resulting in neither being expressed. [6]

Only one Single-nucleotide polymorphism within mir-126 has been identified. A change to the 24th base prevents the processing of the pri-miRNA into the mature miRNA, reducing the suppression of the various targets of mir-126. [7] The frequency of the SNP varies between different ethnic backgrounds and potentially is related to the differential acquisition of human disease.

Targets of mir-126

miRNA binds to target sequences reducing the expression of the target gene. miRNA can bind either directly to DNA preventing transcription or to transcribed mRNA preventing translation and directing the mRNA for degradation. One of the main targets of mir-126 is the host gene EGFL7. Transcription of both occur, however mature mir-126 binds to a complementary sequence within EGFL7 preventing translation of the mRNA resulting in a decrease of EGFL7 protein levels. [8] EGFL7 is known to be involved in cell migration and blood vessel formation, [9] making EGFL7 and mir-126 opportune targets for disease, such as cancers, which require the continual formation of blood vessels to supply the tumour with nutrients and cell migration pathways to mediate tissue invasion.

Involvement in homeostasis

Tissue repair and maintenance are important parts of the life cycle of an organism, cells and tissues must remain in homeostasis to ensure survival. This includes controlled cell death and responses to wounds. During apoptosis cell death, cells release apoptotic bodies containing paracrine signals to neighbouring cells. In endothelial cells, mir-126 is also released with in these bodies are upon absorption in a neighbouring cell induce the CXCL12 dependant vascular protection. [13] CXCL12 binds the receptor CXCR4 actively counteracting apoptosis and recruiting progenitor cells to the site of injury.

Involvement in disease

Cancer

mir-126 has been shown to be both a tumour suppressor and an oncogene depending on the type of cancer. Inhibition of cancer progression occurs through mir-126s negative control of proliferation, migration, invasion and cell survival, while mir-126 also may support cancer progression through the promotion of blood vessel formation and inflammation at the site of activation. [3]

Recently, mir-126 has been used as a tumour marker in a non-invasive diagnostic testing method. Urine samples have been able to identify bladder cancer sufferers apart from those non-effected, as small RNAs are readily excreted through urine. [21]

Diabetes

Low expression levels of many types of miRNA have been observed in type 2 diabetes including: mir-15a, mir-20b, mir-21, mir-124, mir-126, mir-191, mir-197, mir-223, mir-320 and mir-486. [22] Increased expression of mir-28-3p has also been observed. [22] The consequence of misregulation of these miRNAs has not been fully elucidated, however mir-126 has been shown to decrease in expression in response to high glucose levels. [22] The decrease of mir-15a, mir-29b, mir-126 and mir-223 proceedes the manifestation of the disease, making these transcripts a possible target for diagnostic testing for type 2 diabetes.

Cystic fibrosis

Comparisons of cystic fibrosis against non-cystic fibrosis airway epithelial cells shows that various miRNAs are differentially regulated in response to the disease. mir-126 is suspected to play a role in regulating the innate immune responses within Cystic Fibrosis affected lungs. [12]

Allergic asthma

mir-126 increases the immune response to certain antigens resulting in overstimulation of the immune system and allergic asthma. T Helper 2 Cells are affected by mir-126 through a complicated interaction pathway, an increase in mir-126 results in an increase of the response of T Helper 2 Cells. [14]

See also

Related Research Articles

The Let-7 microRNA precursor was identified from a study of developmental timing in C. elegans, and was later shown to be part of a much larger class of non-coding RNAs termed microRNAs. miR-98 microRNA precursor from human is a let-7 family member. Let-7 miRNAs have now been predicted or experimentally confirmed in a wide range of species (MIPF0000002). miRNAs are initially transcribed in long transcripts called primary miRNAs (pri-miRNAs), which are processed in the nucleus by Drosha and Pasha to hairpin structures of about 70 nucleotide. These precursors (pre-miRNAs) are exported to the cytoplasm by exportin5, where they are subsequently processed by the enzyme Dicer to a ~22 nucleotide mature miRNA. The involvement of Dicer in miRNA processing demonstrates a relationship with the phenomenon of RNA interference.

mir-199 microRNA precursor

The miR-199 microRNA precursor is a short non-coding RNA gene involved in gene regulation. miR-199 genes have now been predicted or experimentally confirmed in mouse, human and a further 21 other species. microRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. The mature products are thought to have regulatory roles through complementarity to mRNA.

mir-19 microRNA precursor family

There are 89 known sequences today in the microRNA 19 (miR-19) family but it will change quickly. They are found in a large number of vertebrate species. The miR-19 microRNA precursor is a small non-coding RNA molecule that regulates gene expression. Within the human and mouse genome there are three copies of this microRNA that are processed from multiple predicted precursor hairpins:

mir-1 microRNA precursor family

The miR-1 microRNA precursor is a small micro RNA that regulates its target protein's expression in the cell. microRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give products at ~22 nucleotides. In this case the mature sequence comes from the 3' arm of the precursor. The mature products are thought to have regulatory roles through complementarity to mRNA. In humans there are two distinct microRNAs that share an identical mature sequence, and these are called miR-1-1 and miR-1-2.

mir-7 microRNA precursor

This family represents the microRNA (miRNA) precursor mir-7. This miRNA has been predicted or experimentally confirmed in a wide range of species. miRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. In this case the mature sequence comes from the 5' arm of the precursor. The extents of the hairpin precursors are not generally known and are estimated based on hairpin prediction. The involvement of Dicer in miRNA processing suggests a relationship with the phenomenon of RNA interference.

<span class="mw-page-title-main">EGFL7</span> Protein-coding gene in the species Homo sapiens

EGF-like domain-containing protein 7 is a protein that in humans is encoded by the EGFL7 gene. Intron 7 of EGFL7 hosts the miR-126 microRNA gene.

mir-127

mir-127 microRNA is a short non-coding RNA molecule with interesting overlapping gene structure. miR-127 functions to regulate the expression levels of genes involved in lung development, placental formation and apoptosis. Aberrant expression of miR-127 has been linked to different cancers.

mir-143 RNA molecule

In molecular biology mir-143 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. mir–143 is highly conserved in vertebrates. mir-143 is thought be involved in cardiac morphogenesis but has also been implicated in cancer.

mir-145 Non-coding RNA in the species Homo sapiens

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.

mir-200

In molecular biology, the miR-200 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by binding and cleaving mRNAs or inhibiting translation. The miR-200 family contains miR-200a, miR-200b, miR-200c, miR-141, and miR-429. There is growing evidence to suggest that miR-200 microRNAs are involved in cancer metastasis.

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-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-221 microRNA

In molecular biology, mir-221 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.

miR-27 Family of microRNA precursors found in animals

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

miR-296

miR-296 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. This sequence then associates with RISC which effects RNA interference.

In molecular biology mir-301 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-365 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

References

  1. ↑ van Solingen C, Seghers L, Bijkerk R, Duijs JM, Roeten MK, van Oeveren-Rietdijk AM, Baelde HJ, Monge M, Vos JB, de Boer HC, Quax PH, Rabelink TJ, van Zonneveld AJ (2009). "Antagomir-mediated silencing of endothelial cell specific microRNA-126 impairs ischemia-induced angiogenesis". Journal of Cellular and Molecular Medicine. 13 (8A): 1577–85. doi:10.1111/j.1582-4934.2008.00613.x. PMC   3828868 . PMID   19120690.
  2. ↑ Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, Richardson JA, Bassel-Duby R, Olson EN (2008). "The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis". Dev Cell. 15 (2): 261–71. doi:10.1016/j.devcel.2008.07.002. PMC   2685763 . PMID   18694565.
  3. 1 2 Meister J, Schmidt MH (2010). "miR-126 and miR-126*: new players in cancer". ScientificWorldJournal. 10: 2090–100. doi: 10.1100/tsw.2010.198 . PMC   5763667 . PMID   20953557.
  4. ↑ Musiyenko A, Bitko V, Barik S (2008). "Ectopic expression of miR-126*, an intronic product of the vascular endothelial EGF-like 7 gene, regulates prostein translation and invasiveness of prostate cancer LNCaP cells". Journal of Molecular Medicine. 86 (3): 313–22. doi:10.1007/s00109-007-0296-9. PMC   3263384 . PMID   18193184.
  5. ↑ Harris TA, Yamakuchi M, Kondo M, Oettgen P, Lowenstein CJ (2010). "Ets-1 and Ets-2 regulate the expression of microRNA-126 in endothelial cells". Arterioscler Thromb Vasc Biol. 30 (10): 1990–7. doi:10.1161/ATVBAHA.110.211706. PMC   3121560 . PMID   20671229.
  6. 1 2 3 Saito Y, Friedman JM, Chihara Y, Egger G, Chuang JC, Liang G (2009). "Epigenetic therapy upregulates the tumor suppressor microRNA-126 and its host gene EGFL7 in human cancer cells". Biochem Biophys Res Commun. 379 (3): 726–31. doi:10.1016/j.bbrc.2008.12.098. PMID   19116145.
  7. ↑ Harnprasopwat R, Ha D, Toyoshima T, Lodish H, Tojo A, Kotani A (2010). "Alteration of processing induced by a single nucleotide polymorphism in pri-miR-126". Biochem Biophys Res Commun. 399 (2): 117–22. doi:10.1016/j.bbrc.2010.07.009. PMC   3056433 . PMID   20621067.
  8. ↑ Sun YQ, Zhang F, Bai YF, Guo LL (2010). "[miR-126 modulates the expression of epidermal growth factor-like domain 7 in human umbilical vein endothelial cells in vitro]". Nan Fang Yi Ke da Xue Xue Bao. 30 (4): 767–70. PMID   20423846.
  9. 1 2 Sun Y, Bai Y, Zhang F, Wang Y, Guo Y, Guo L (2010). "miR-126 inhibits non-small cell lung cancer cells proliferation by targeting EGFL7". Biochem Biophys Res Commun. 391 (3): 1483–9. doi:10.1016/j.bbrc.2009.12.098. PMID   20034472.
  10. 1 2 Feng R, Chen X, Yu Y, Su L, Yu B, Li J, Cai Q, Yan M, Liu B, Zhu Z (2010). "miR-126 functions as a tumour suppressor in human gastric cancer". Cancer Lett. 298 (1): 50–63. doi:10.1016/j.canlet.2010.06.004. PMID   20619534.
  11. ↑ Crawford M, Brawner E, Batte K, Yu L, Hunter MG, Otterson GA, Nuovo G, Marsh CB, Nana-Sinkam SP (2008). "MicroRNA-126 inhibits invasion in non-small cell lung carcinoma cell lines". Biochem Biophys Res Commun. 373 (4): 607–12. doi:10.1016/j.bbrc.2008.06.090. PMID   18602365.
  12. 1 2 Oglesby IK, Bray IM, Chotirmall SH, Stallings RL, O'Neill SJ, McElvaney NG, Greene CM (2010). "miR-126 is downregulated in cystic fibrosis airway epithelial cells and regulates TOM1 expression". Journal of Immunology. 184 (4): 1702–9. doi: 10.4049/jimmunol.0902669 . PMID   20083669.
  13. 1 2 Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan L, Denecke B, Hristov M, Köppel T, Jahantigh MN, Lutgens E, Wang S, Olson EN, Schober A, Weber C (2009). "Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection". Sci Signal. 2 (100): ra81. doi:10.1126/scisignal.2000610. PMID   19996457. S2CID   45583628.
  14. 1 2 Mattes J, Collison A, Plank M, Phipps S, Foster PS (2009). "Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease". Proceedings of the National Academy of Sciences, USA. 106 (44): 18704–9. Bibcode:2009PNAS..10618704M. doi: 10.1073/pnas.0905063106 . PMC   2773983 . PMID   19843690.
  15. 1 2 Liu B, Peng XC, Zheng XL, Wang J, Qin YW (2009). "MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo". Lung Cancer. 66 (2): 169–75. doi:10.1016/j.lungcan.2009.01.010. PMID   19223090.
  16. 1 2 Zhang J, Du YY, Lin YF, Chen YT, Yang L, Wang HJ, Ma D (2008). "The cell growth suppressor, mir-126, targets IRS-1". Biochem Biophys Res Commun. 377 (1): 136–40. doi:10.1016/j.bbrc.2008.09.089. PMID   18834857.
  17. ↑ Shen WF, Hu YL, Uttarwar L, Passegue E, Largman C (2008). "MicroRNA-126 regulates HOXA9 by binding to the homeobox". Mol Cell Biol. 28 (14): 4609–19. doi:10.1128/MCB.01652-07. PMC   2447122 . PMID   18474618.
  18. ↑ Li Z, Chen J (2011). "In vitro functional study of miR-126 in leukemia". MicroRNA and Cancer. Methods in Molecular Biology. Vol. 676. pp. 185–95. doi:10.1007/978-1-60761-863-8_13. ISBN   978-1-60761-862-1. PMID   20931398.
  19. ↑ Li XM, Wang AM, Zhang J, Yi H (2010). "Down-regulation of miR-126 expression in colorectal cancer and its clinical significance". Med Oncol. 28 (4): 1054–7. doi:10.1007/s12032-010-9637-6. PMID   20680522. S2CID   24084013.
  20. ↑ Png, K. J.; Halberg, N.; Yoshida, M.; Tavazoie, S. F. (2011). "A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells". Nature. 481 (7380): 190–194. doi:10.1038/nature10661. PMID   22170610. S2CID   205227054.
  21. ↑ Hanke M, Hoefig K, Merz H, Feller AC, Kausch I, Jocham D, Warnecke JM, Sczakiel G (2009). "A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer". Urol Oncol. 28 (6): 655–61. doi:10.1016/j.urolonc.2009.01.027. PMID   19375957.
  22. 1 2 3 Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A, Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M (2010). "Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes". Circ Res. 107 (6): 810–7. doi: 10.1161/CIRCRESAHA.110.226357 . PMID   20651284.

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