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-126 is a human microRNA that is expressed only in

miR-126 is located within the 7th intron of the EGFL7 gene which resides on human chromosome 9.^[3]

mir-126*

mir-126* is the complementary strand to mir-126 which forms once the double stranded pri-miRNA is cleaved and the two strands denature, separating. mir-126* is less abundantly found in organisms than mir-126 and fewer roles in regulating gene expression have been identified. However, mir-126* has recently been implicated in the silencing of

Only one Single-nucleotide polymorphism within mir-126 has been identified. A change to the 24th base prevents the processing of the pri-miRNA into the mature miRNA, reducing the suppression of the various targets of mir-126.^[7] The frequency of the SNP varies between different ethnic backgrounds and potentially is related to the differential acquisition of human disease.

Targets of mir-126

miRNA binds to target sequences reducing the expression of the target gene. miRNA can bind either directly to DNA preventing

• CRK, a protein involved in intracellular signal pathways involved in regulating cellular adhesion, proliferation, migration and invasion.^[10][11]
• TNF-alpha signalling pathways.^[12]
• Production of
  CXCL12, a chemokine, is regulated by mir-126.^[13]
• PU.1. PU.1 negatively regulates GATA3 expression, altering the response of the T helper 2 cells.^[14]
• VEGF-A protein production is reduced as mir-126 binds to the 3' untranslated region of the VEGF-A mRNA.^[15]
• IRS-1 inhibiting the cell cycle from progressing from G₀/G₁into S phase.^[16]
• HOXA9, mir-126 modulates HOXA9 expression in haematopoietic cells.^[17] HOX genes are important developmental regulatory genes.

Involvement in homeostasis

Tissue repair and maintenance are important parts of the life cycle of an organism, cells and tissues must remain in homeostasis to ensure survival. This includes controlled cell death and responses to wounds. During apoptosis cell death, cells release apoptotic bodies containing paracrine signals to neighbouring cells. In endothelial cells, mir-126 is also released with in these bodies are upon absorption in a neighbouring cell induce the CXCL12 dependant vascular protection.^[13] CXCL12 binds the receptor CXCR4 actively counteracting apoptosis and recruiting progenitor cells to the site of injury.

Involvement in disease

Cancer

mir-126 has been shown to be both a

• mir-126 and mir126* are overexpressed in acute myeloid leukemia.^[18]
• mir-126 expression is reduced in colorectal cancer.^[19]
• mir-126 expression is reduced in
  gastric cancer.^[10]
• mir-126 expression is reduced in lung cancer cell lines.^[15]
• mir-126 expression is reduced in prostate cancer^[6] and bladder cancer.^[6]
• mir-126 expression is reduced in breast cancer.^[16] It also suppresses metastatic endothelial recruitment, angiogenesis and colonisation, through interaction with its target genes IGFBP2, PITPNC1, and MERTK.^[20]
• Increased expression of mir-126 inhibits cell proliferation of
  non-small cell lung carcinoma cells in vitro and prevents tumour growth through the targeting of EGFL7.^[9]

Comparisons of cystic fibrosis against non-cystic fibrosis airway epithelial cells shows that various miRNAs are differentially regulated in response to the disease. mir-126 is suspected to play a role in regulating the innate immune responses within Cystic Fibrosis affected lungs.^[12]

Allergic asthma

mir-126 increases the immune response to certain antigens resulting in overstimulation of the immune system and

• MicroRNA
• EGFL7

References