Mir-31

Last updated
mir-31
RF00661.png
Conserved secondary structure of mir-31
Identifiers
Symbolmir-31
Rfam RF00661
miRBase family MIPF0000064
Other data
RNA type microRNA
Domain(s) Eukaryota
PDB structures PDBe

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. [1] 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. [2] Mir-31-5p has also been observed upregulated in Zinc Deficient rats compared to normal in ESCC (Esophageal Squamous Cell Carcinoma) and in other types of cancers when using this animal model. [3] There has also been observed a strong encapsulation of tumour cells expressing miR-31, as well as a reduced cell survival rate. [4] 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.

Contents

Functions

mir-31 has been linked to Duchenne muscular dystrophy − a genetic disorder characterised by a lack of the protein dystrophin − as a potential therapeutic target. Duchenne muscular dystrophy is caused by mutations arising in the dystrophin gene, which impair the translation of dystrophin through the formation of premature termination codons. [5]

miR-31 overexpression is more abundant in human Duchenne muscular dystrophy than in healthy controls, with levels remaining high only in Duchenne muscular dystrophy myoblasts. miR-31 levels in healthy controls are instead decreased with the onset of cell differentiation. miR-31 is part of the circuit controlling late muscle differentiation by repression of dystrophin synthesis, and its expression is localised specifically to regenerating myoblasts of dystrophic muscles. [6] miR-31 is believed to repress the expression of dystrophin by antisense binding of the dystrophin mRNA 3′ untranslated region, and in this way it is thought that miR-31 manipulation could aid treatment for Duchenne muscular dystrophy.

Applications

In serous ovarian cancer, miR-31 is frequently deleted and is the most underexpressed microRNA in this cancer type. It has been shown to affect the levels of gene transcription factor p53, responsible for encoding the tumour suppressor protein p53. [7] Cancer cell lines with an inactive p53 pathway show a vulnerability to miR-31 overexpression, whilst there is resistance to overexpression in cell lines with a functional p53 pathway. [8] miR-31 overexpression is associated with a better prognosis in tumours, suggesting that therapeutic delivery of miR-31 may be beneficial in patients with p53-deficient cancers. Conversely, in gastric cancer miR-31 levels have been found to be significantly lower in tumour cells relative to healthy cells, meaning further potential for use as a diagnostic marker. [9] However, high expression levels of miR-31 correlate to shorter survival in patients with malignant pleural mesothelioma, whereas longer survival has been associated with normal/low expression of miR-31 from blood-based samples. [10] Furthermore, in vivo, anti-miR-31 has proved to reduce miR-31-5p overexpression suppressing the esophageal preneoplasia in Zinc deficient rats. This leads to the repression of miR-31-5p target Stk40 by the inhibition of the STK40-NF-κΒ-controlled inflammatory pathway, with resultant decreased cellular proliferation and activated apoptosis. Notably Zn replenishment is able to restore the regulation of miR-31-5p targets leading to a normal esophageal phenotype. [11] miR-31 has further been shown to negatively regulate FOXP3, the master regulator in T-lymphocyte development and function. [12] This is through direct binding of miR-31 at its target site in the 3′UTR of FOXP3 mRNA. [13]

Related Research Articles

<span class="mw-page-title-main">Dystrophin</span> Rod-shaped cytoplasmic protein

Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costamere or the dystrophin-associated protein complex (DAPC). Many muscle proteins, such as α-dystrobrevin, syncoilin, synemin, sarcoglycan, dystroglycan, and sarcospan, colocalize with dystrophin at the costamere. It has a molecular weight of 427 kDa

<span class="mw-page-title-main">Duchenne muscular dystrophy</span> Type of muscular dystrophy

Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy that primarily affects boys. Muscle weakness usually begins around the age of four, and worsens quickly. Muscle loss typically occurs first in the thighs and pelvis followed by the arms. This can result in trouble standing up. Most are unable to walk by the age of 12. Affected muscles may look larger due to increased fat content. Scoliosis is also common. Some may have intellectual disability. Females with a single copy of the defective gene may show mild symptoms.

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.

The dystrophin-associated protein complex, also known as the dystrophin-associated glycoprotein complex is a multiprotein complex that includes dystrophin and the dystrophin-associated proteins. It is one of the two protein complexes that make up the costamere in striated muscle cells. The other complex is the integrin-vinculin-talin complex.

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-129 microRNA precursor family

The miR-129 microRNA precursor is a small non-coding RNA molecule that regulates gene expression. This microRNA was first experimentally characterised in mouse and homologues have since been discovered in several other species, such as humans, rats and zebrafish. The mature sequence is excised by the Dicer enzyme from the 5' arm of the hairpin. It was elucidated by Calin et al. that miR-129-1 is located in a fragile site region of the human genome near a specific site, FRA7H in chromosome 7q32, which is a site commonly deleted in many cancers. miR-129-2 is located in 11p11.2.

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.

mIRN21 Non-coding RNA in the species Homo sapiens

microRNA 21 also known as hsa-mir-21 or miRNA21 is a mammalian microRNA that is encoded by the MIR21 gene.

miR-155 Non-coding RNA in the species Homo sapiens

MiR-155 is a microRNA that in humans is encoded by the MIR155 host gene or MIR155HG. MiR-155 plays a role in various physiological and pathological processes. Exogenous molecular control in vivo of miR-155 expression may inhibit malignant growth, viral infections, and enhance the progression of cardiovascular diseases.

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-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-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-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-361 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. For example, miR-361-5p might act as a suppressor in triple-negative breast cancer (TNBC) by targeting RQCD1 to inhibit the EGFR/PI3K/Akt signaling pathway.

In molecular biology mir-504 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-885 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

mIR489 Non-coding RNA in the species Homo sapiens

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

miR-324-5p is a microRNA that functions in cell growth, apoptosis, cancer, epilepsy, neuronal differentiation, psychiatric conditions, cardiac disease pathology, and more. As a microRNA, it regulates gene expression through targeting mRNAs. Additionally, miR-324-5p is both an intracellular miRNA, meaning it is commonly found within the microenvironment of the cell, and one of several circulating miRNAs found throughout the body. Its presence throughout the body both within and external to cells may contribute to miR-324-5p's wide array of functions and role in numerous disease pathologies – especially cancer – in various organ systems.

References

  1. ↑ O'Day, E; Lal, A (2010). "MicroRNAs and their target gene networks in breast cancer". Breast Cancer Research. 12 (2): 201. doi: 10.1186/bcr2484 . PMC   2879559 . PMID   20346098.
  2. ↑ Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szász AM, Wang ZC, et al. (2009). "A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis". Cell. 137 (6): 1032–1046. doi:10.1016/j.cell.2009.03.047. PMC   2766609 . PMID   19524507.
  3. ↑ Fong LY, Taccioli C, Jing R, Smalley KJ, Alder H, Jiang Y, Fadda P, Farber JL, Croce CM (2016). "MicroRNA dysregulation and esophageal cancer development depend on the extent of zinc dietary deficiency". Oncotarget. 7 (10): 10723–38. doi:10.18632/oncotarget.7561. PMC   4905434 . PMID   26918602.
  4. ↑ Valastyan S, Chang A, Benaich N, Reinhardt F, Weinberg RA (2011). "Activation of miR-31 function in already-established metastases elicits metastatic regression". Genes Dev. 25 (6): 646–659. doi:10.1101/gad.2004211. PMC   3059837 . PMID   21406558.
  5. ↑ Cacchiarelli, D; Incitti, T; Martone, J; Cesana, M; Cazzella, V; Santini, T; Sthandier, O; Bozzoni, I (February 2011). "miR-31 modulates dystrophin expression: new implications for Duchenne muscular dystrophy therapy". EMBO Reports. 12 (2): 136–141. doi:10.1038/embor.2010.208. PMC   3049433 . PMID   21212803.
  6. ↑ Cacchiarelli D, Incitti T, Martone J, Cesana M, Cazzella V, Santini T, et al. (2011). "miR-31 modulates dystrophin expression: new implications for Duchenne muscular dystrophy therapy". EMBO Rep. 12 (2): 136–141. doi:10.1038/embor.2010.208. PMC   3049433 . PMID   21212803.
  7. ↑ Louis DN, von Deimling A, Chung RY, Rubio MP, Whaley JM, Eibl RH, et al. (1993). "Comparative study of p53 gene and protein alterations in human astrocytic tumors". J Neuropathol Exp Neurol. 52 (1): 31–38. doi:10.1097/00005072-199301000-00005. PMID   8381161. S2CID   21836130.
  8. ↑ Creighton CJ, Fountain MD, Yu Z, Nagaraja AK, Zhu H, Khan M, et al. (2010). "Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers". Cancer Res. 70 (5): 1906–1915. doi:10.1158/0008-5472.CAN-09-3875. PMC   2831102 . PMID   20179198.
  9. ↑ Zhang, Y; Guo, J; Li, D; Xiao, B; Miao, Y; Jiang, Z; Zhuo, H (September 2010). "Down-regulation of miR-31 expression in gastric cancer tissues and its clinical significance". Medical Oncology (Northwood, London, England). 27 (3): 685–689. doi:10.1007/s12032-009-9269-x. PMID   19598010. S2CID   22851497.
  10. ↑ Reid, Glen (June 2015). "MicroRNAs in mesothelioma: from tumour suppressors and biomarkers to therapeutic targets". Journal of Thoracic Disease. 7 (6): 1031–1040. doi:10.3978/j.issn.2072-1439.2015.04.56. PMC   4466421 . PMID   26150916.
  11. ↑ Cristian Taccioli; Michela Garofalo; Hongping Chen; Yubao Jiang; Guidantonio Malagoli Tagliazucchi; Gianpiero Di Leva; Hansjuerg Alder; Paolo Fadda; Justin Middleton; Karl J Smalley; Tommaso Selmi; Srivatsava Naidu; John L Farber; Carlo M Croce; Louise Y Fong (2015). "Repression of Esophageal Neoplasia and Inflammatory Signaling by Anti-miR-31 Delivery In Vivo". J Natl Cancer Inst. 107 (11): 1–11. doi: 10.1093/jnci/djv220 . PMC   4675101 . PMID   26286729.
  12. ↑ Rouas R, Fayyad-Kazan H, El Zein N, Lewalle P, Rothé F, Simion A, et al. (2009). "Human natural Treg microRNA signature: role of microRNA-31 and microRNA-21 in FOXP3 expression". Eur J Immunol. 39 (6): 1608–1618. doi: 10.1002/eji.200838509 . PMID   19408243.
  13. ↑ Divekar AA, Dubey S, Gangalum PR, Singh RR (2011). "Dicer insufficiency and microRNA-155 overexpression in lupus regulatory T cells: an apparent paradox in the setting of an inflammatory milieu". J Immunol. 186 (2): 924–930. doi:10.4049/jimmunol.1002218. PMC   3038632 . PMID   21149603.

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