MICRO RNA 149; MIR149

miRNA149
MIR149-5p

Other entities represented in this entry:
MICRO RNA 149, INCLUDED; MIR149, INCLUDED
MICRO RNA 149-3p, INCLUDED; MIR149-3p, INCLUDED

HGNC Approved Gene Symbol: MIR149

Cytogenetic location: 2q37.3 Genomic coordinates (GRCh38): 2:240,456,001-240,456,089 (from NCBI)

▼ Description

MicroRNAs (miRNAs), such as MIR149, are RNAs of about 22 nucleotides that negatively regulate gene expression by binding to complementary target mRNA sequences. Most miRNAs are processed from large primary RNAs (pri-miRNAs) into precursor RNAs (pre-miRNAs) of about 80 nucleotides that contain a stem-loop structure. Some pre-miRNAs, including pre-miRNA149, generate functional miRNAs from both the 5-prime and 3-prime ends of the stem-loop structure. These miRNAs may be differentially expressed, and the less-abundant miRNA is given a star designation. MIR149 and MIR149* are processed from the 5-prime and 3-prime ends of pre-miRNA149, respectively (Lin et al., 2010).

▼ Cloning and Expression

Jin et al. (2011) noted that miR149 and miR149* are highly conserved among mammals.

▼ Mapping

Jin et al. (2011) stated that the MIR149 gene is located within the first intron of the GPC1 gene.

By genomic sequence analysis, Wang et al. (2013) mapped the MIR149 gene to chromosome 2q37.3.

▼ Gene Function

Lin et al. (2010) had previously found that MIR149 was significantly downregulated in neuroblastomas from a clinical high-risk group compared with those from low- and intermediate-risk groups. They found that overexpression of MIR149 induced apoptosis in Be2C neuroblastoma cells and HeLa cells. MIR149 repressed expression of AKT1 (164730), E2F1 (189971), and BMYB (601415). In contrast, MIR149 failed to repress these putative targets. Reporter gene assays revealed that MIR149 directly inhibited expression of AKT1 and ER2F1, but not BMYB. Analysis of primary neuroblastomas revealed a significant inverse correlation between MIR149 and E2F1 expression. Overexpression of MIR149 did not neutralize the apoptotic effect of MIR149, suggesting that MIR149 and MIR149 do not form a duplex in vivo.

By RT-PCR analysis, Jin et al. (2011) showed that miR149 was upregulated in melanoma cells in response to endoplasmic reticulum (ER) stress. MIR149 is embedded within the first intron of the GPC1 gene, and Jin et al. (2011) identified a putative p53 (TP53; 191170)-binding site upstream of the GPC1 translational start site. Under ER stress, p53 levels were increased in melanoma cells, and p53 transcriptionally upregulated miR149 expression by binding to the p53-binding region of the GPC1 gene. Upregulated miR149 under ER stress targeted the 3-prime UTR of GSK3A (606784) to downregulate cellular levels of GSK3A. Decreased expression of GSK3A led to upregulation of MCL1 (159552) in melanoma cells, resulting in protection of melanoma cells from ER stress-induced apoptosis. Further analysis suggested that the p53-miR149-GSK3A-MCL1 pathway may provide an advantage for melanoma cell survival and, conceivably, resistance to treatment.

Wang et al. (2013) determined that the MIR149 gene resides within a CpG island and that it was hypermethylated in human colorectal cancer cell lines. DNA demethylation or downregulation of the DNA methyltransferases DNMT1 (126375) and DNMT3B (602900) elevated MIR149 expression. MIR149 expression was reduced in colorectal cancers compared with adjacent normal tissues, and downregulation of MIR149 was associated with greater depth of tumor invasion and lower 5-year survival. Expression analysis identified 889 genes that exhibited over 2-fold decrease in expression following transfection of a MIR149 mimic. Using a reporter gene, Wang et al. (2013) confirmed direct downregulation of SP1 (189906) by MIR149. Overexpression of both MIR149 and SP1 revealed that MIR149 inhibited cancer cell invasion, but not proliferation, by targeting SP1.