Contributors:

miR-17-92a-1 cluster host gene

  • genes

1. Introduction

The MIR17HG gene provides instructions for making the miR-17~92 microRNA (miRNA) cluster. MiRNAs are short pieces of RNA, a chemical cousin of DNA. These molecules control gene expression by blocking protein production. The miR-17~92 cluster includes six miRNAs: miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a-1. MiRNAs in this cluster control the expression of hundreds of genes. These miRNAs help regulate signaling pathways that direct several cellular processes involved in growth and development, including cell growth and division (proliferation), cell maturation (differentiation), and the self-destruction of cells (apoptosis). Studies suggest that the miR-17~92 cluster is necessary for normal development of the skeleton, heart, kidneys, lungs, and nervous system.

The MIR17HG gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous.

2. Health Conditions Related to Genetic Changes

2.1. Feingold syndrome

Genetic changes that reduce the amount of the MIR17HG gene cause Feingold syndrome type 2. This developmental disorder is characterized by abnormalities of the fingers and toes, particularly shortening of the second and fifth fingers (brachymesophalangy). Other common features include an unusually small head size (microcephaly) and learning disabilities. The mutations involved in this condition, known as 13q31.3 microdeletions, remove (delete) a small region of chromosome 13 that includes the MIR17HG gene and sometimes part or all of other nearby genes. Loss of the MIR17HG gene is thought to underlie the characteristic features of the disorder, although loss of other genes may play a role in some cases.

Deletion of one copy of the MIR17HG gene reduces the amount of miR-17~92 cluster miRNAs available to control the activity of specific genes during development before birth. While it is likely that the resulting disruption of signaling pathways leads to the problems with growth and development characteristic of Feingold syndrome type 2, it remains unclear exactly how a shortage of miR-17~92 cluster miRNAs causes the specific features of the condition.

2.2. Other disorders

Genetic changes, called microduplications, that result in an extra copy of the MIR17HG gene have been associated with developmental problems in a small number of people. Some individuals with these microduplications have overgrowth of the skeleton, resulting in extra fingers (polydactyly) and an unusually large head size (macrocephaly). Others with these microduplications have impaired growth, leading to short fingers (brachydactyly) and short stature. Affected individuals may also have features of autism spectrum disorder, which is characterized by impaired communication and social interaction. Researchers suggest that an extra copy of the MIR17HG gene disrupts normal skeletal growth, although they are unsure why the microduplications can either increase or reduce growth.

2.3. Cancers

Genetic changes that result in extra copies of the MIR17HG gene have been found in cancer. These genetic changes likely occur when DNA makes a copy of itself (replicates) in preparation for cell division. Errors in the replication process can result in one or more extra copies of a gene within a cell, which is known as gene amplification. The amplifications are somatic, which means they are not inherited but instead occur in cells that give rise to the tumor. Gene amplifications involving MIR17HG have been found in a cancer of immune system cells called diffuse large B-cell lymphoma. Such amplifications are thought to increase the amount of miR-17~92 miRNAs. The resulting alterations to cell signaling pathways may lead to too much cell proliferation or too little apoptosis. As a result, cells can grow and divide uncontrollably, leading to the development of cancer.

3. Other Names for This Gene

  • C13orf25
  • FGLDS2
  • FLJ14178
  • LINC00048
  • MIHG1
  • miR-17-92
  • MIRH1
  • MIRHG1
  • NCRNA00048

This entry is adapted from https://medlineplus.gov/genetics/gene/mir17hg

References

  1. de Pontual L, Yao E, Callier P, Faivre L, Drouin V, Cariou S, Van Haeringen A,Geneviève D, Goldenberg A, Oufadem M, Manouvrier S, Munnich A, Vidigal JA,Vekemans M, Lyonnet S, Henrion-Caude A, Ventura A, Amiel J. Germline deletion of the miR-17∼92 cluster causes skeletal and growth defects in humans. Nat Genet.2011 Sep 4;43(10):1026-30. doi: 10.1038/ng.915.
  2. Fang LL, Wang XH, Sun BF, Zhang XD, Zhu XH, Yu ZJ, Luo H. Expression,regulation and mechanism of action of the miR-17-92 cluster in tumor cells(Review). Int J Mol Med. 2017 Dec;40(6):1624-1630. doi: 10.3892/ijmm.2017.3164.
  3. Grote LE, Repnikova EA, Amudhavalli SM. Expanding the phenotype of feingoldsyndrome-2. Am J Med Genet A. 2015 Dec;167A(12):3219-25. doi:10.1002/ajmg.a.37368.
  4. Hemmat M, Rumple MJ, Mahon LW, Strom CM, Anguiano A, Talai M, Nguyen B, Boyar FZ. Short stature, digit anomalies and dysmorphic facial features are associated with the duplication of miR-17 ~ 92 cluster. Mol Cytogenet. 2014 Apr 16;7:27.doi: 10.1186/1755-8166-7-27.
  5. Kannu P, Campos-Xavier AB, Hull D, Martinet D, Ballhausen D, Bonafé L.Post-axial polydactyly type A2, overgrowth and autistic traits associated with a chromosome 13q31.3 microduplication encompassing miR-17-92 and GPC5. Eur J MedGenet. 2013 Aug;56(8):452-7. doi: 10.1016/j.ejmg.2013.06.001.Review. Erratum in: Eur J Med Genet. 2014 Feb;57(2-3):123-4.
  6. Mirzamohammadi F, Kozlova A, Papaioannou G, Paltrinieri E, Ayturk UM,Kobayashi T. Distinct molecular pathways mediate Mycn and Myc-regulated miR-17-92microRNA action in Feingold syndrome mouse models. Nat Commun. 2018 Apr10;9(1):1352. doi: 10.1038/s41467-018-03788-7.
  7. Mogilyansky E, Rigoutsos I. The miR-17/92 cluster: a comprehensive update onits genomics, genetics, functions and increasingly important and numerous rolesin health and disease. Cell Death Differ. 2013 Dec;20(12):1603-14. doi:10.1038/cdd.2013.125. Review.
More
This entry is offline, you can click here to edit this entry!
Top