Mir-205

Last updated
mir-205
MiR-205 secondary structure.png
miR-205 microRNA secondary structure and sequence conservation
Identifiers
Symbolmir-205
Rfam RF00656
miRBase family MIPF0000058
NCBI Gene 406988
HGNC 31583
OMIM 613147
Other data
RNA type microRNA
Domain(s) Eukaryota; Euteleostomi;
PDB structures PDBe

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. [1]

Contents

The miR-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) and miR-205 are frequently silenced in advanced cancer. Studies has shown that—by targeting the transcriptional repressors of E-cadherin, ZEB1 and ZEB2 miR-205 is involved in epithelial to mesenchymal transition (EMT) and tumor invasion. [2]

Recently, miR-200 silencing was also reported in cancer stem cells, implying that miR-200 deregulation is a key event in multiple levels of tumor biology. The cause of miR-200 silencing in naturally occurring cancer cells, however, remains largely unknown. [3]

Genomic locations

Members of miR-200 family including miR -205 are found clustered at two locations in the human genome : 1142000 – 1144500 in chromosome 1 and 6942000 – 6944500 in chromosome 12. Short genomic distance between members suggests that they may function collaboratively and are highly related in sequence. [2]

miR-205 targets

Role of miR-205 in Cancer

Studies have demonstrated that miR-205 has a role in both normal development and cancer.

Breast Cancer

miR-205 was found to be highly expressed in stem cell-enriched populations from the mouse mammary gland, and thus may play a function in normal mammary stem cell maintenance. [4]

An increasing amount of experimental evidence shows that microRNAs can have a causal role in breast cancer tumorigenesis as a novel class of oncogenes or tumor suppressor genes, depending on the targets they regulate. It was found down-modulated in breast tumors compared with normal breast tissue. [5] [6] miR-205 expression is associated with survival in breast cancer. Patients with higher expression have higher probability of survival. [7] This down regulation was also observed in breast cancer cell lines, including MCF-7 and MDA-MB-231 compared to the non-malignant cell line MCF-10A. It directly targets HER3 receptor, vascular endothelial growth factor A (VEGF-A) through interaction with putative binding site in the 3'-untranslated region (3'-UTR) of ErbB3 and VEGF-A. [8] miR-205 inhibits the activation of the downstream mediator Akt. miR-205 was found to be able to interfere with the proliferative pathway mediated by HER receptor family. [5] [6]

Ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage independent growth, as well as cell invasion. Furthermore, miR-205 was shown to suppress lung metastasis in an animal model. [5]

Prostate cancer

Research has shown that miR-205 was significantly down-regulated in prostate cancer compared with match normal tissue. Its re-expression induced apoptosis and cell cycle arrest and resulted in a mesenchymal-to-epithelial transition, such as up-regulation of E-cadherin and reduction of cell locomotion and invasion, and in the down-regulation of several oncogenes known to be involved in disease progression (i.e., interleukin 6, caveolin-1, EZH2). [9]

It also impaired cell growth, migration, clonability, and invasiveness of prostate cancer cells. Micro-RNA-205 induced the expression of tumor suppressor genes IL-24 and IL-32 at both the messenger RNA and protein levels.

miR-205 exerts a tumor-suppressive effect in human prostate by counteracting epithelial-to-mesenchymal transition and reducing cell migration/invasion, at least in part through the down-regulation of protein kinase Cepsilon. [9] miR-205 activated tumor suppressor genes by targeting specific sites in their promoters. These results corroborate a newly identified function that miRNAs have in regulating gene expression at the transcriptional level. The specific activation of tumor suppressor genes (e.g., IL-24, IL-32) or other dysregulated genes by miRNA may contribute to a novel therapeutic approach for the treatment of prostate cancer. [10]

Bladder Cancer

From a study on transcriptional regulation of the miR-200 and miR-205 loci in bladder tumors and bladder cell lines, the miR-200 and miR-205 loci were found specifically silenced and gain promoter hypermethylation and repressive chromatin marks in muscle invasive bladder tumors and undifferentiated bladder cell lines. miR-200c expression is significantly correlated with early stage T1 bladder tumor progression, and propose miR-200 and miR-205 silencing and DNA hypermethylation as possible prognostic markers in bladder cancer. [3]

Lung Cancer

has-miR-205 was identified as a highly specific marker for squamous cell lung carcinoma. Has-miR-205 is a highly accurate marker for lung cancer of squamous histology. Diagnostic assay can provide highly accurate subclassification of NSCLC patients. [11]

Colorectal Cancer

Mir-205 has been found to be significantly deregulated in colorectal cancer. [12] Elevated expression levels of miR-205 have been shown to be associated with mucinous colorectal cancers and mucin-producing ulcerative colitis-associated colon cancers, but not with sporadic colonic adenocarcinoma that lack mucinous components. [13] Overexpression of miR-205 in an intestinal epithelial cell line (Caco-2 subclone) promoted accumulation of mucus-secreting goblet cell-like cells and mucin production and MUC2 mRNA expression were enhanced in-vitro. [13]

Cellular and molecular biological functions

It is still not clear how miR-205 plays in directing stem cell fate. A study on mammary-gland stem or progenitor cells showed that miR-205 over expression led to an expansion of the progenitor-cell population, decreased cell size and increased cellular proliferation. [4]

Research also shows miR-205 might regulate the expression of the tumor-suppressor protein PTEN. Several other putative and previously validated miR-205 targets include ZEB1 and ZEB2. [14]

Inhibition of microRNA-205 increased the number of phosphorylated FAK and phosphorylated Pax, and decreased filamentous actin. microRNA-205 has down-regulating effect on cell motility in NHCEKs. [15]

microRNA-205 (miR-205) and miR-184 coordinately regulate the lipid phosphatase SHIP2 for Akt survival signaling in keratinocytes. [16]

miR-205 also interacts with a specific target in the 3'-UTR sequence of MED1, which plays an important role in placental development, and silences MED1 expression in human trophoblasts exposed to hypoxia. [17]

Potentials in clinical applications

microRNA (miRNA) expression profiles are being intensively investigated for their involvement in carcinogenesis.

Detection of metastatic head and neck squamous cell carcinoma

The presence of cervical lymph node metastases in head and neck squamous cell carcinoma (HNSCC) is the strongest determinant of patient prognosis. Owing to the impact of nodal metastases on patient survival, a system for sensitive and accurate detection is required. Studies has shown that the expression of microRNA-205 (miR-205) is highly specific for squamous epithelium and can be used as a molecular marker for the detection of metastatic HNSCC. [18]

See also

Related Research Articles

The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell–cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal cells that can differentiate into a variety of cell types. EMT is essential for numerous developmental processes including mesoderm formation and neural tube formation. EMT has also been shown to occur in wound healing, in organ fibrosis and in the initiation of metastasis in cancer progression.

<span class="mw-page-title-main">Keratin 8</span>

Keratin, type II cytoskeletal 8 also known as cytokeratin-8 (CK-8) or keratin-8 (K8) is a keratin protein that is encoded in humans by the KRT8 gene. It is often paired with keratin 18.

miR-218 microRNA precursor family Non-coding RNA

miR-218 microRNA precursor is a small non-coding RNA that regulates gene expression by antisense binding.

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">H19 (gene)</span> Negative regulation (or limiting) of body weight and cell proliferation

H19 is a gene for a long noncoding RNA, found in humans and elsewhere. H19 has a role in the negative regulation of body weight and cell proliferation. This gene also has a role in the formation of some cancers and in the regulation of gene expression. .

A metastasis suppressor is a protein that acts to slow or prevent metastases from spreading in the body of an organism with cancer. Metastasis is one of the most lethal cancer processes. This process is responsible for about ninety percent of human cancer deaths. Proteins that act to slow or prevent metastases are different from those that act to suppress tumor growth. Genes for about a dozen such proteins are known in humans and other animals.

<span class="mw-page-title-main">MTA3</span> Protein-coding gene in the species Homo sapiens

Metastasis-associated protein MTA3 is a protein that in humans is encoded by the MTA3 gene. MTA3 protein localizes in the nucleus as well as in other cellular compartments MTA3 is a component of the nucleosome remodeling and deacetylate (NuRD) complex and participates in gene expression. The expression pattern of MTA3 is opposite to that of MTA1 and MTA2 during mammary gland tumorigenesis. However, MTA3 is also overexpressed in a variety of human cancers.

mir-126

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.

miR-137

In molecular biology, miR-137 is a short non-coding RNA molecule that functions to regulate the expression levels of other genes by various mechanisms. miR-137 is located on human chromosome 1p22 and has been implicated to act as a tumor suppressor in several cancer types including colorectal cancer, squamous cell carcinoma and melanoma via cell cycle control.

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-184 Non-coding microRNA molecule

In molecular biology, miR-184 microRNA is a short non-coding RNA molecule. MicroRNAs (miRNAs) function as posttranscriptional regulators of expression levels of other genes by several mechanisms. Several targets for miR-184 have been described, including that of mediators of neurological development, apoptosis and it has been suggested that miR-184 plays an essential role in development.

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-203

In molecular biology miR-203 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 messenger RNA cleavage. miR-203 has been identified as a skin-specific microRNA, and it forms an expression gradient that defines the boundary between proliferative epidermal basal progenitors and terminally differentiating suprabasal cells. It has also been found upregulated in psoriasis and differentially expressed in some types of cancer.

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-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-138

miR-138 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-138 precursor is the microRNA mir-138.

In molecular biology mir-452 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-708 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. miR-708 is located on chromosome 11q14.1 and is endcoded in intron 1 of the ODZ4 gene. It is most highly expressed in the brain and eyes, and has a supposed role in endoplasmic reticular stress of the eye.

mIR489 Non-coding RNA in the species Homo sapiens

MicroRNA 489 is a miRNA that in humans is encoded by the MIR489 gene.

References

  1. ↑ Bartel DP (2004). "MicroRNAs: genomics, biogenesis, mechanism, and function". Cell. 116 (2): 281–97. doi: 10.1016/S0092-8674(04)00045-5 . PMID   14744438.
  2. 1 2 Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ (2008). "The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1". Nat Cell Biol. 10 (5): 593–601. doi:10.1038/ncb1722. PMID   18376396. S2CID   9513443.
  3. 1 2 Wiklund ED, Bramsen JB, Hulf T, Dyrskjøt L, Ramanathan R, Hansen TB, Villadsen SB, Gao S, Ostenfeld MS, Borre M, Peter ME, Ørntoft TF, Kjems J, Clark SJ (2010). "Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer". Int J Cancer. 128 (6): 1327–34. doi: 10.1002/ijc.25461 . PMID   20473948.
  4. 1 2 Greene SB, Herschkowitz JI, Rosen JM (2010). "The ups and downs of miR-205: Identifying the roles of miR-205 in mammary gland development and breast cancer". RNA Biol. 7 (3): 300–4. doi:10.4161/rna.7.3.11837. PMC   3008649 . PMID   20436283.
  5. 1 2 3 Iorio MV, Casalini P, Piovan C, Di Leva G, Merlo A, Triulzi T, Ménard S, Croce CM, Tagliabue E (2009). "microRNA-205 regulates HER3 in human breast cancer". Cancer Res. 69 (6): 2195–200. doi: 10.1158/0008-5472.CAN-08-2920 . PMID   19276373.
  6. 1 2 Wu H, Zhu S, Mo YY (2009). "Suppression of cell growth and invasion by miR-205 in breast cancer". Cell Res. 19 (4): 439–48. doi:10.1038/cr.2009.18. PMC   2664859 . PMID   19238171.
  7. ↑ 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.
  8. ↑ Xiao Y, Humphries B, Yang C, Wang Z (November 2019). "MiR-205 Dysregulations in Breast Cancer: The Complexity and Opportunities". Non-Coding RNA. 5 (4): 53. doi: 10.3390/ncrna5040053 . PMC   6958506 . PMID   31752366.
  9. 1 2 Gandellini P, Folini M, Longoni N, Pennati M, Binda M, Colecchia M, Salvioni R, Supino R, Moretti R, Limonta P, Valdagni R, Daidone MG, Zaffaroni N (2009). "miR-205 Exerts tumor-suppressive functions in human prostate through down-regulation of protein kinase Cepsilon". Cancer Res. 69 (6): 2287–95. doi: 10.1158/0008-5472.CAN-08-2894 . hdl: 2434/69700 . PMID   19244118.
  10. ↑ Majid S, Dar AA, Saini S, Yamamura S, Hirata H, Tanaka Y, Deng G, Dahiya R (2010). "MicroRNA-205–directed transcriptional activation of tumor suppressor genes in prostate cancer". Cancer. 116 (24): 5637–49. doi:10.1002/cncr.25488. PMC   3940365 . PMID   20737563.
  11. ↑ Lebanony D, Benjamin H, Gilad S, Ezagouri M, Dov A, Ashkenazi K, Gefen N, Izraeli S, Rechavi G, Pass H, Nonaka D, Li J, Spector Y, Rosenfeld N, Chajut A, Cohen D, Aharonov R, Mansukhani M (2009). "Diagnostic assay based on hsa-miR-205 expression distinguishes squamous from nonsquamous non-small-cell lung carcinoma". J Clin Oncol. 27 (12): 2030–7. doi: 10.1200/JCO.2008.19.4134 . PMID   19273703.
  12. ↑ Kara M, Yumrutas O, Ozcan O, Celik O, Bozgeyik E, Bozgeyik I, Tasdemir S (2015). "Differential expression of cancer-associated genes and their regulatory miRNAs in colorectal carcinoma". Gene. 567 (1): 81–6. doi: 10.1016/j.gene.2015.04.065 . PMID   25925209.
  13. 1 2 Eyking A, Reis H, Frank M, Gerken G, Schmid KW, Cario E (2016). "MiR-205 and MiR-373 Are Associated with Aggressive Human Mucinous Colorectal Cancer". PLOS ONE. 11 (6): e0156871. Bibcode:2016PLoSO..1156871E. doi: 10.1371/journal.pone.0156871 . PMC   4894642 . PMID   27271572.
  14. ↑ Greene SB, Gunaratne PH, Hammond SM, Rosen JM (2010). "A putative role for microRNA-205 in mammary epithelial cell progenitors". J Cell Sci. 123 (Pt 4): 606–18. doi:10.1242/jcs.056812. PMC   2818197 . PMID   20103531.
  15. ↑ Li J, Bai H, Zhu Y, Wang XY, Wang F, Zhang JW, Lavker RM, Yu J (2010). "Antagomir dependent microRNA-205 reduction enhances adhesion ability of human corneal epithelial keratinocytes". Chin Med Sci J. 25 (2): 65–70. doi: 10.1016/s1001-9294(10)60024-7 . PMID   20598226.
  16. ↑ Yu J, Peng H, Ruan Q, Fatima A, Getsios S, Lavker RM (2010). "MicroRNA-205 promotes keratinocyte migration via the lipid phosphatase SHIP2". FASEB J. 24 (10): 3950–9. doi:10.1096/fj.10-157404. PMC   2996908 . PMID   20530248.
  17. ↑ Mouillet JF, Chu T, Nelson DM, Mishima T, Sadovsky Y (2010). "MiR-205 silences MED1 in hypoxic primary human trophoblasts". FASEB J. 24 (6): 2030–9. doi:10.1096/fj.09-149724. PMC   2874470 . PMID   20065103.
  18. ↑ Fletcher AM, Heaford AC, Trask DK (2008). "Detection of metastatic head and neck squamous cell carcinoma using the relative expression of tissue-specific mir-205". Transl Oncol. 1 (4): 202–8. doi:10.1593/tlo.08163. PMC   2582169 . PMID   19043531.

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