Table 4.
Reports of miR-132 Expression and Function.
| Pathway | Finding | Profiling Method | Validated mRNA Target | References |
| Angiogenesis | • miR-132 expression in HUVEC cells is induced by VEGF and bFGF | qRT-PCR | p250RasGAP | [12] |
| • miR-132 is highly expressed in the endothelium of human breast carcinoma (n = 12 tumors) and hemangiomas (n = 68 tissues) but not in normal endothelium | LNA probes (in situ hybridization) | |||
| • Transfection of HUVEC cells with miR-132 increases their proliferative and tube-forming capacity | ||||
| • Treatment of HUVEC cells with anti-miR-132 significantly decreases VEGF-induced phosphorylation of MEK-1 | ||||
| • Targeted delivery of anti-miR-132 to tumor endothelium (through a liposome carrier and αvβ3 integrin-targeting peptide) suppresses angiogenesis and tumor burden in an orthotopic xenograft model of human breast cancer | ||||
| Immune function/inflammation | • miR-132 is highly upregulated in lymphatic endothelial cells following infection with Kaposi sarcoma-associated herpesvirus and after infection of monocytes with herpes simplex virus and human cytomegalovirus | miRNA microarray and qRT-PCR | p300 | [43] |
| • miR-132 is upregulated in primary human macrophages treated with LPS | Spotted microarray (customized, in-house miRNA microarray) and qRT-PCR | AChE | [15] | |
| • Overexpression of miR-132 through lentiviral infections downregulates acetylcholine activity in primary bone marrow-derived macrophages | ||||
| • miR-132 is one of three miRNAs upregulated in NK cells following prolonged treatment with IL-12 and negatively regulates the IL-12 signaling pathway, modulating NK cell responsiveness to further IL-12 stimulation | qRT-PCR | STAT4 | [28] | |
| • miR-132 is significantly upregulated in IgE-activated human and mouse mast cells | miRNA microarray and qRT-PCR | HB-EGF | [29] | |
| • miR-132 is one of five miRNAs significantly upregulated in peripheral blood mononuclear cells isolated from patients with rheumatoid arthritis (n = 16) compared to controls (n = 4) | qRT-PCR | [35] | ||
| • miR-132 is induced in primary human adipose-derived stem cells following serum deprivation. Overexpression of miR-132 in this cell line promotes an increase in proinflammatory chemokines IL-8 and MCP-1 and promotes NF-κB activation (through an increase in acetylated p65) | qRT-PCR | SIRT1 | [31] | |
| Glial/neuronal signaling | •Overexpression of miR-132 in embryonic stem cells reduces the differentiation of dopamine neurons | qRT-PCR | [16] | |
| • miR-132 is significantly upregulated in cultured cortical neuronal cells in response to BDNF treatment | qRT-PCR | NR2B, NR2A, GluR1* | [14] | |
| • miR-132 is significantly upregulated in cultured astroglial cells in response to bFGF | qRT-PCR | [44] | ||
| • miR-132 expression is significantly upregulated in LβT2 pituitary gonadotrope cells, following treatment with GnRH | qRT-PCR | [45] | ||
| • miR-132 expression is rapidly induced by synaptic activity in hippocampal neurons. miR-132 expression promotes dendrite growth and branching | qRT-PCR | p250RhoGAP | [27] | |
| • miR-132 is required for dendrite maturation in newborn neurons of the adult hippocampus | qRT-PCR | [13] | ||
| Neurologic disease | •miR-132 expression is significantly downregulated in the prefrontal cortex of schizophrenia subjects (n = 35; n = 16) compared to normal health controls (n = 34; n = 15), in two independent cohorts | miRNA microarray and qRT-PCR | DNMT3A, GATA2, DPYSL3 | [18] |
| • miR-132 is one of four miRNAs identified as important regulators of τ exon 10 splicing and is downregulated in sporadic progressive supranuclear palsy dementia cases (n = 8) compared to nondimentia controls (n = 8) | qRT-PCR | PTBP2 | [30] | |
| • miR-132 identified as a regulator of seizure-induced neuronal death. Depletion of hippocampal miR-132 levels using LNA-modified anti-miR-132 oligonucleotides (antagomirs) protected mice against seizure damage, in a mouse model of epileptic tolerance | TaqMan Low Density Array (Applied Biosystem, Foster City, CA) | [46] | ||
| • miR-132 is one of nine miRNAs downregulated in two transgenic mouse models of Huntington disease | miRNA microarray and qRT-PCR | [17] | ||
| Carcinogenesis | • miR-132 is significantly upregulated in PDAC (n = 11), compared to adjacent benign (n = 6) and normal (n = 4) tissue | qRT-PCR | Rb1 | [26] |
| • miR-132 is overexpressed in lung tumor tissue (n = 123) and pancreatic tumor tissue (n = 39) compared to normal control tissue (n = 123 and 12, respectively) | miRNA microarray (customized) | [11] | ||
| • miR-132 was part of a five-miRNA panel distinguishing responders and nonresponders to ifosfamide therapy (n = 27 high-grade osteosarcoma cases), with miR-132 reduced in responders | TaqMan Low Density Array | [47] |
HUVEC indicates human umbilical vein endothelial cell; VEGF, vascular endothelial growth factor; bFGF, basic fibroblast growth factor; LNA, locked nucleic acid; MEK-1, MAPK/ERK kinase 1; LPS, lipopolysaccharide; AChE, acetylcholinesterase; NK, natural killer; STAT4, signal transducer and activator of transcription 4; IL-12, interleukin-12; HB-EGF, heparin-binding EGF-like growth factor; IL-8, interleukin-8; MCP-1, monocyte chemoattractant protein; NF-κB, nuclear factor-κ-light-chain enhancer of activated B cells; SIRT1, sirtuin 1; BDNF, brain-derived neurotrophic factor; NR2B, glutamate receptor, ionotrophic, N-methyl D-aspartate 2B; NR2A, glutamate receptor, ionotropic, N-methyl D-aspartate 2A, GluR1, glutamate receptor, ionotropic, AMPA 1; GnRH, gonadotropin-releasing hormone; DNMT3A, DNA (cytosine-5-)-methyltransferase 3 α; GATA2, GATA-binding protein 2; DPYSL3, dihydropyrimidinase-like 3; PTBP2, polypyrimidine tract-binding protein 2; PDAC, pancreatic ductal adenocarcinoma; Rb1, retinoblastoma 1.
With the exception of references [11], [15], and [18], microarrays were Agilent technology (Santa Clara, CA).
Indirect targets.