Jump to content

MiR-203: Difference between revisions

Edit links
From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
Cdr36 (talk | contribs)
56 edits
No edit summary
Cdr36 (talk | contribs)
56 edits
No edit summary
Line 18: Line 18:
}}
}}


In molecular biology '''mir-203 microRNA''' is a short [[non-coding RNA|non-coding RNA]] molecule. [[MicroRNA]]s function to regulate the expression levels of other genes by several mechanisms, such as translational repression and Argonaute-catalyzed mRNA cleavage<ref name="pmid19167326">{{cite journal |author=Bartel DP |title=MicroRNAs: target recognition and regulatory functions. |journal=Cell |volume=136 |issue=2 |pages=215-33 |year=2009 |pmid=19167326}}</ref><ref name="pmid14744438">{{cite journal |author=Bartel DP |title=MicroRNAs: genomics, biogenesis, mechanism, and function. |journal=Cell |volume=116 |issue=2 |pages=281-97 |year=2004 |pmid=14744438}}</ref>. miR-203 has been identified as a skin-specific miRNA, and it forms an expression gradient that defines the boundary between proliferative epidermal basal progenitors and terminally differentiating suprabasal cells.<ref name="pmid18311128">{{cite journal |author=Yi R, Poy MN, Stoffel M, Fuchs E |title=A skin microRNA promotes differentiation by repressing ‘stemness’. |journal=Nature |volume=452 |issue=7184 |pages=225-9 |year=2008 |pmid=18311128}}</ref> It has also been found upregulated in psoriasis<ref name="pmid18853072">{{cite journal |author=Bostjancic E, Glavac D |title=Importance of microRNAs in skin morphogenesis and diseases. |journal=Acta Dermatovenerol Alp Panonica Adriat |volume=17 |issue=3 |pages=95-102 |year=2008 |pmid=18853072}}</ref> and differentially expressed in some types of cancer<ref name="pmid20652642">{{cite journal |author=Ikenaga N, Ohuchida K, Mizumoto K, Yu J, Kayashima T, Sakai H, Fujita H, Nakata K, Tanaka M |title=MicroRNA-203 Expression as a New Prognostic Marker of Pancreatic Adenocarcinoma. |journal=Ann Surg Oncol |volume= |issue= |pages= |year=2010 |pmid=20652642}}</ref><ref name="pmid20219920">{{cite journal |author=Melar-New M, Laimins LA |title=Human papillomaviruses modulate expression of microRNA 203 upon epithelial differentiation to control levels of p63 proteins. |journal=J Virol |volume=84 |issue=10 |pages=5212-21 |year=2010 |pmid=20219920}}</ref>.
In molecular biology '''mir-203 microRNA''' is a short [[non-coding RNA|non-coding RNA]] molecule. [[MicroRNA]]s function to regulate the expression levels of other genes by several mechanisms, such as translational repression and Argonaute-catalyzed mRNA cleavage<ref name="pmid19167326">{{cite journal |author=Bartel DP |title=MicroRNAs: target recognition and regulatory functions. |journal=Cell |volume=136 |issue=2 |pages=215-33 |year=2009 |pmid=19167326}}</ref><ref name="pmid14744438">{{cite journal |author=Bartel DP |title=MicroRNAs: genomics, biogenesis, mechanism, and function. |journal=Cell |volume=116 |issue=2 |pages=281-97 |year=2004 |pmid=14744438}}</ref>. miR-203 has been identified as a skin-specific miRNA, and it forms an expression gradient that defines the boundary between proliferative epidermal basal progenitors and terminally differentiating suprabasal cells<ref name="pmid18311128">{{cite journal |author=Yi R, Poy MN, Stoffel M, Fuchs E |title=A skin microRNA promotes differentiation by repressing ‘stemness’. |journal=Nature |volume=452 |issue=7184 |pages=225-9 |year=2008 |pmid=18311128}}</ref>. It has also been found upregulated in psoriasis<ref name="pmid18853072">{{cite journal |author=Bostjancic E, Glavac D |title=Importance of microRNAs in skin morphogenesis and diseases. |journal=Acta Dermatovenerol Alp Panonica Adriat |volume=17 |issue=3 |pages=95-102 |year=2008 |pmid=18853072}}</ref> and differentially expressed in some types of cancer<ref name="pmid20652642">{{cite journal |author=Ikenaga N, Ohuchida K, Mizumoto K, Yu J, Kayashima T, Sakai H, Fujita H, Nakata K, Tanaka M |title=MicroRNA-203 Expression as a New Prognostic Marker of Pancreatic Adenocarcinoma. |journal=Ann Surg Oncol |volume= |issue= |pages= |year=2010 |pmid=20652642}}</ref><ref name="pmid20219920">{{cite journal |author=Melar-New M, Laimins LA |title=Human papillomaviruses modulate expression of microRNA 203 upon epithelial differentiation to control levels of p63 proteins. |journal=J Virol |volume=84 |issue=10 |pages=5212-21 |year=2010 |pmid=20219920}}</ref>.


== Introduction ==
== Introduction ==
MicroRNAs are short (20-22nt), non-coding RNA molecules involved in the regulation of mRNAs by targeting their 3’ UTR and affecting their stability or promoting their silencing or degradation[cite]. MicroRNAs are likely to play roles in most cellular processes, including proliferation, development, differentiation and apoptosis<ref name="pmid20652642"/>. MicroRNAs are located in intergenic and intragenic regions, and are transcribed as pri-miRNA by Pol II or Pol III<ref name="pmid18853072"/>. They then undergo extensive post-transcriptional modifications, starting with the processing of the pri-miRNA in the nucleus to generate a 70-100 nt long pre-miRNA by ribonucleases Drosha and DGCR8. This pre-miRNA is then transported out of the nucleus by Exportin-5, and is then further processed by Dicer into a mature 18-25 nt long double stranded microRNA<ref name="pmid20885409">{{cite journal |author=Garzon R, Marcucci G, Croce CM |title=Targeting microRNAs in cancer: rationale, strategies and challenges. |journal=Nat Rev Drug Discov. |volume=9 |issue=10 |pages=775-89 |year=2010 |pmid=20885409}}</ref>. The guide strand of the miRNA is then loaded into RISC (RNA-inducing silencing complex)<ref name="pmid20885409"/> and is then able to bind its target. The passenger miRNA, denoted by a star, is commonly degraded, though this is not always the case[reference].
MicroRNAs are short (20-22nt), non-coding RNA molecules involved in the regulation of messenger RNAs (mRNAs) by pairing with their 3’ UTR and affecting their stability<ref name="pmid18853072"/> or directing their silencing or degradation<ref name="pmid19167326"/>. MicroRNAs are likely to play roles in most cellular processes, including proliferation, development, differentiation and apoptosis<ref name="pmid20652642"/>. They are located in intergenic and intragenic regions, and are transcribed as pri-miRNA by Pol II or Pol III<ref name="pmid18853072"/>. They then undergo extensive post-transcriptional modifications, starting with the processing of the pri-miRNA in the nucleus to generate a 70-100 nt long pre-miRNA by ribonucleases Drosha and DGCR8. This pre-miRNA is then transported out of the nucleus by Exportin-5, and is then further processed by Dicer into a mature 18-25 nt long double stranded microRNA<ref name="pmid20885409">{{cite journal |author=Garzon R, Marcucci G, Croce CM |title=Targeting microRNAs in cancer: rationale, strategies and challenges. |journal=Nat Rev Drug Discov. |volume=9 |issue=10 |pages=775-89 |year=2010 |pmid=20885409}}</ref>. The guide strand of the miRNA is then loaded into RISC (RNA-inducing silencing complex)<ref name="pmid20885409"/> and is then able to pair with its target. The passenger strand, denoted by a star, is commonly degraded, though this is not always the case<ref name="pmid20613982">{{cite journal |author=Guo L, Lu Z |title=The fate of miRNA* strand through evolutionary analysis: implication for degradation as merely carrier strand or potential regulatory molecule? |journal=PLoS One |volume=5 |issue=6 |pages=e11387 |year=2010 |pmid=20613982}}</ref>.


miR-203 is a microRNA that is specifically expressed in keratinocytes (the most abundant cell type in the epidermis) and in normal conditions promotes epidermal differentiation by restricting proliferative potential and inducing cell-cycle exit<ref name="pmid18311128"/>. It does so by repressing p63, an essential regulator of stem cell maintenance in epithelial stratified tissues<ref name="pmid18311128"/>.
miR-203 is a microRNA that is specifically expressed in keratinocytes (the most abundant cell type in the epidermis) and in normal conditions promotes epidermal differentiation by restricting proliferative potential and inducing cell-cycle exit<ref name="pmid18311128"/>. It does so by repressing p63, an essential regulator of stem cell maintenance in epithelial stratified tissues<ref name="pmid18311128"/>.

Revision as of 19:44, 8 November 2010

mir-203
miR-203 microRNA secondary structure and sequence conservation
Identifiers
Symbolmir-203
RfamRF00696
miRBase familyMIPF0000108
NCBI Gene406986
HGNC31581
OMIM611899
Other data
RNA typemicroRNA
Domain(s)Eukaryota; Euteleostomi
PDB structuresPDBe

In molecular biology mir-203 microRNA is a short non-coding RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms, such as translational repression and Argonaute-catalyzed mRNA cleavage[1][2]. miR-203 has been identified as a skin-specific miRNA, and it forms an expression gradient that defines the boundary between proliferative epidermal basal progenitors and terminally differentiating suprabasal cells[3]. It has also been found upregulated in psoriasis[4] and differentially expressed in some types of cancer[5][6].

Introduction

MicroRNAs are short (20-22nt), non-coding RNA molecules involved in the regulation of messenger RNAs (mRNAs) by pairing with their 3’ UTR and affecting their stability[4] or directing their silencing or degradation[1]. MicroRNAs are likely to play roles in most cellular processes, including proliferation, development, differentiation and apoptosis[5]. They are located in intergenic and intragenic regions, and are transcribed as pri-miRNA by Pol II or Pol III[4]. They then undergo extensive post-transcriptional modifications, starting with the processing of the pri-miRNA in the nucleus to generate a 70-100 nt long pre-miRNA by ribonucleases Drosha and DGCR8. This pre-miRNA is then transported out of the nucleus by Exportin-5, and is then further processed by Dicer into a mature 18-25 nt long double stranded microRNA[7]. The guide strand of the miRNA is then loaded into RISC (RNA-inducing silencing complex)[7] and is then able to pair with its target. The passenger strand, denoted by a star, is commonly degraded, though this is not always the case[8].

miR-203 is a microRNA that is specifically expressed in keratinocytes (the most abundant cell type in the epidermis) and in normal conditions promotes epidermal differentiation by restricting proliferative potential and inducing cell-cycle exit[3]. It does so by repressing p63, an essential regulator of stem cell maintenance in epithelial stratified tissues[3].


Localization

In humans, miR-203 is located in an intergenic region in chromosome 14, position 104583742-104583851. In mouse, it is found in chromosome 12[7].

Evidence

This miRNA was predicted using computational tools by comparison to mouse and tiger blowfish sequences. It has been validated in zebrafish and its expression confirmed in humans[9] [7].

Targets

miR-203 has two validated and conserved targets, p63 and SOCS3 (suppressor of cytokine signaling 3). p63 is an essential regulator of stem cell maintenance in stratified epithelial tissues[3]. By repressing the expression of this protein, miR-203 is able to induce the differentiation program in suprabasal layers of skin. SOCS3

Foetal skin development

Yi R et al. showed that in mice, the expression of miR-203 is significantly upregulated between E13.5 and E15.5, suggesting that it may be absent from multipotent progenitors of single-layered epidermis, but is induced upon stratification and differentiation[3]. It also was expressed at high levels in differentiating cells such as hair follicles, epidermis and sebaceous glands.

A study by Wei T et al. demonstrated that in humans, miR-203 expression is first detectable at 17 weeks gestation in the suprabasal layers of epidermis, and this localization was the same in the adult skin[10].

Role in carcinogenesis

miR-203 has been found overexpressed in pancreatic adenocarcinoma and shows correlation with poor prognosis in patients that had underwent pancreatectomy, and has been suggested as a new prognostic marker for this disease [5]. Also, miR-203 has been identified as target of human papillomavirus (HPV) protein E7[6], which causes its downregulation and thus de-repression of p63 and its downstream targets, ensuring proliferative potential on the host cell, required for the virus to replicate. High levels of miR-203 are inhibitory of HPV amplification[6].

Role in psoriasis

See also

References

  1. ^ a b Bartel DP (2009). "MicroRNAs: target recognition and regulatory functions". Cell. 136 (2): 215–33. PMID 19167326.
  2. ^ Bartel DP (2004). "MicroRNAs: genomics, biogenesis, mechanism, and function". Cell. 116 (2): 281–97. PMID 14744438.
  3. ^ a b c d e Yi R, Poy MN, Stoffel M, Fuchs E (2008). "A skin microRNA promotes differentiation by repressing 'stemness'". Nature. 452 (7184): 225–9. PMID 18311128.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ a b c Bostjancic E, Glavac D (2008). "Importance of microRNAs in skin morphogenesis and diseases". Acta Dermatovenerol Alp Panonica Adriat. 17 (3): 95–102. PMID 18853072.
  5. ^ a b c Ikenaga N, Ohuchida K, Mizumoto K, Yu J, Kayashima T, Sakai H, Fujita H, Nakata K, Tanaka M (2010). "MicroRNA-203 Expression as a New Prognostic Marker of Pancreatic Adenocarcinoma". Ann Surg Oncol. PMID 20652642.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ a b c Melar-New M, Laimins LA (2010). "Human papillomaviruses modulate expression of microRNA 203 upon epithelial differentiation to control levels of p63 proteins". J Virol. 84 (10): 5212–21. PMID 20219920.
  7. ^ a b Garzon R, Marcucci G, Croce CM (2010). "Targeting microRNAs in cancer: rationale, strategies and challenges". Nat Rev Drug Discov. 9 (10): 775–89. PMID 20885409.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Guo L, Lu Z (2010). "The fate of miRNA* strand through evolutionary analysis: implication for degradation as merely carrier strand or potential regulatory molecule?". PLoS One. 5 (6): e11387. PMID 20613982.
  9. ^ Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, Lin C, Socci ND, Hermida L, Fulci V, Chiaretti S, Foa R, Schliwka J, Fuchs U, Novosel A, Muller RU, Schermer B, Bissels U, Inman J, Phan Q, Chien M (2007). "A mammalian microRNA expression atlas based on small RNA library sequencing". Cell. 129 (7): 1401–14. PMID 17604727.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ Wei T, Orfanidis K, Xu N, Janson P, StÃ¥hle M, Pivarcsi A, Sonkoly E (2010). "The expression of microRNA-203 during human skin morphogenesis". Exp Dermatol. 19 (9): 854–6. PMID 20698882.{{cite journal}}: CS1 maint: multiple names: authors list (link)

Further reading

  1. ^ Stanczyk J, Ospelt C, Karouzakis E, Filer A, Raza K, Kolling C, Gay R, Buckley CD, Tak PP, Gay S, Kyburz D (2010). "Altered expression of miR-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation". Arthritis Rheum. PMID 20981815.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ McKenna DJ, McDade SS, Patel D, McCance DJ (2010). "MicroRNA 203 expression in keratinocytes is dependent on regulation of p53 levels by E6". J Virol. 84 (20): 10644–52. PMID 20702634.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ Furuta M, Kozaki KI, Tanaka S, Arii S, Imoto I, Inazawa J (2010). "miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma". Carcinogenesis. 31 (5): 766–76. PMID 19843643.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Sonkoly E, Wei T, Pavez Loriè E, Suzuki H, Kato M, Törmä H, StÃ¥hle M, Pivarcsi A (2010). "Protein kinase C-dependent upregulation of miR-203 induces the differentiation of human keratinocytes". J Invest Dermatol. 130 (1): 124–34. PMID 19759552.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Bueno MJ, Pérez de Castro I, Gómez de Cedrón M, Santos J, Calin GA, Cigudosa JC, Croce CM, Fernández-Piqueras J, Malumbres M (2008). "Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression". Cancer Cell. 13 (6): 496–506. PMID 18538733.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ Lena AM, Shalom-Feuerstein R, Rivetti di Val Cervo P, Aberdam D, Knight RA, Melino G, Candi E (2008). "miR-203 represses 'stemness' by repressing DeltaNp63". Cell Death Differ. 15 (7): 1187–95. PMID 18483491.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Garzon R, Marcucci G, Croce CM (2010). "Targeting microRNAs in cancer: rationale, strategies and challenges". Nat Rev Drug Discov. 9 (10): 775–89. PMID 20885409.{{cite journal}}: CS1 maint: multiple names: authors list (link)

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=MiR-203&oldid=395597924"