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.[1] miRNAs are transcribed as ~70 nucleotide precursors (modelled here) 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.

mir-7 microRNA precursor
Predicted secondary structure and sequence conservation of mir-7
Identifiers
Symbolmir-7
RfamRF00053
miRBaseMI0000263
miRBase familyMIPF0000022
Other data
RNA typeGene; miRNA
Domain(s)Eukaryota
GO0035195 0035068
SO0001244
PDB structuresPDBe

Mature miRNA-7 is derived from three microRNA precursors in the human genome, miR-7-1, miR-7-2 and miR-7-3. miRNAs are numbered based on the sequence of the mature RNA.

miR-7 is directly regulated by the transcription factor HoxD10.[2]

miRNAs are thought to have regulatory roles through complementarity to mRNA. miR-7 is essential for the maintenance of regulatory stability under conditions of environmental flux.[3] It plays an important role in controlling mRNA expression. The miR-7 gene is found in most sequenced Urbilateria species, and the sequence of its mature miRNA product is perfectly conserved from annelids to humans, indicating a strong functional conservation.[3]

Targets of miR-7

Bioinformatic predictions suggest that the human EGFR mRNA 3'-untranslated region contains three microRNA-7 (miR-7) target sites, which are not conserved across mammals.[4] In Drosophila photoreceptor cells, miR-7 controls epidermal growth factor receptor (EGFR) signaling and promotes photoreceptor differentiation.[5] Among other targets of miR-7 are insulin-like growth factor 1 receptor (IGF1R) and PIK3CD,[6] E(spl) gene family [7] and Pak1 (cancer cells).[2] c-Fos is also a target of miR-7b in mice.[8] Pax6 translation in the lateral wall of the subventricular zone of developed mice is post-transcriptionally regulated by miRNA-7a mediated gene silencing, which is necessary to control the rate of dopaminergic neuron production in the olfactory bulb.[9]

Clinical relevance

Multiple roles and targets of miR-7 as well as its expression pattern were linked to regulatory mechanisms and pathogenesis in glioblastoma,[10] breast cancer[11] and other types of cancers,[4][6][12] as well as in schizophrenia[13] and visual abnormalities.[14] Inhibition of the motility, invasiveness, anchorage-independent growth, and tumorigenic potential of highly invasive breast cancer cells through the introduction of miR-7 suggests a strong therapeutic potential of miR-7.[2][15]

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References
  1. "miRNA gene family: mir-7 (92 sequences)". MiRBase. Archived from the original on 2007-09-29.
  2. Reddy SD, Ohshiro K, Rayala SK, Kumar R (October 2008). "MicroRNA-7, a homeobox D10 target, inhibits p21-activated kinase 1 and regulates its functions". Cancer Research. 68 (20): 8195–200. doi:10.1158/0008-5472.CAN-08-2103. PMC 3636563. PMID 18922890.
  3. Li X, Cassidy JJ, Reinke CA, Fischboeck S, Carthew RW (April 2009). "A microRNA imparts robustness against environmental fluctuation during development". Cell. 137 (2): 273–82. doi:10.1016/j.cell.2009.01.058. PMC 2674871. PMID 19379693.
  4. Webster RJ, Giles KM, Price KJ, Zhang PM, Mattick JS, Leedman PJ (February 2009). "Regulation of epidermal growth factor receptor signaling in human cancer cells by microRNA-7". The Journal of Biological Chemistry. 284 (9): 5731–41. doi:10.1074/jbc.M804280200. PMID 19073608.
  5. Li X, Carthew RW (December 2005). "A microRNA mediates EGF receptor signaling and promotes photoreceptor differentiation in the Drosophila eye". Cell. 123 (7): 1267–77. doi:10.1016/j.cell.2005.10.040. PMID 16377567.
  6. Jiang L, Liu X, Chen Z, Jin Y, Heidbreder CE, Kolokythas A, Wang A, Dai Y, Zhou X (November 2010). "MicroRNA-7 targets IGF1R (insulin-like growth factor 1 receptor) in tongue squamous cell carcinoma cells". The Biochemical Journal. 432 (1): 199–205. doi:10.1042/BJ20100859. PMC 3130335. PMID 20819078.
  7. Stark A, Brennecke J, Russell RB, Cohen SM (December 2003). "Identification of Drosophila MicroRNA targets". PLoS Biology. 1 (3): E60. doi:10.1371/journal.pbio.0000060. PMC 270017. PMID 14691535.
  8. Lee HJ, Palkovits M, Young WS (October 2006). "miR-7b, a microRNA up-regulated in the hypothalamus after chronic hyperosmolar stimulation, inhibits Fos translation". Proceedings of the National Academy of Sciences of the United States of America. 103 (42): 15669–74. doi:10.1073/pnas.0605781103. PMC 1622879. PMID 17028171.
  9. de Chevigny A (2012). "miR-7a regulation of Pax6 controls spatial origin of forebrain dopaminergic neurons". Nature Neuroscience. 15: 1120–1126. doi:10.1038/nn.3142.
  10. Kefas B, Godlewski J, Comeau L, Li Y, Abounader R, Hawkinson M, Lee J, Fine H, Chiocca EA, Lawler S, Purow B (May 2008). "microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma". Cancer Research. 68 (10): 3566–72. doi:10.1158/0008-5472.CAN-07-6639. PMID 18483236.
  11. Foekens JA, Sieuwerts AM, Smid M, Look MP, de Weerd V, Boersma AW, Klijn JG, Wiemer EA, Martens JW (September 2008). "Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer". Proceedings of the National Academy of Sciences of the United States of America. 105 (35): 13021–6. Bibcode:2008PNAS..10513021F. doi:10.1073/pnas.0803304105. PMC 2529088. PMID 18755890.
  12. Veerla S, Lindgren D, Kvist A, Frigyesi A, Staaf J, Persson H, Liedberg F, Chebil G, Gudjonsson S, Borg A, Månsson W, Rovira C, Höglund M (May 2009). "MiRNA expression in urothelial carcinomas: important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31". International Journal of Cancer. 124 (9): 2236–42. doi:10.1002/ijc.24183. PMID 19127597.
  13. Perkins DO, Jeffries CD, Jarskog LF, Thomson JM, Woods K, Newman MA, Parker JS, Jin J, Hammond SM (2007). "microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder". Genome Biology. 8 (2): R27. doi:10.1186/gb-2007-8-2-r27. PMC 1852419. PMID 17326821.
  14. Arora A, McKay GJ, Simpson DA (September 2007). "Prediction and verification of miRNA expression in human and rat retinas". Investigative Ophthalmology & Visual Science. 48 (9): 3962–7. doi:10.1167/iovs.06-1221. PMID 17724173.
  15. Czech MP (March 2006). "MicroRNAs as therapeutic targets". The New England Journal of Medicine. 354 (11): 1194–5. doi:10.1056/NEJMcibr060065. PMID 16540623.

Further reading

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