MIR1226

Locus Summary

Gene:MIR1226; microRNA 1226
Aliases: MIRN1226, mir-1226, hsa-mir-1226
Location:3p21.31
Summary:microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
Databases:miRBase, HGNC, GeneCard, Gene
Source:NCBIAccessed: 06 August, 2015

Cancer Overview

Research Indicators

Publications Per Year (1990-2015)
Graph generated 06 August 2015 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 06 August, 2015 using data from PubMed, MeSH and CancerIndex

Specific Cancers (2)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

MicroRNA Function

Numbers shown below represent number of publications held in OncomiRDB database for Oncogenic and Tumor-Suppressive MicroRNAs.

TissueTarget Gene(s)Regulator(s)MIR1226 Function in CancerEffect
breast (1)
-breast cancer (1)
MUC1 (1)
increase reactive oxygen species (1)
reduce the mitochondrial transmembrane potential (1)
decrease cell survival (1)
tumor-suppressive (1)

Source: OncomiRDB Wang D. et al. Bioinformatics 2014, 30(15):2237-2238.

Latest Publications: MIR1226 (cancer-related)

Borkowski R, Du L, Zhao Z, et al.
Genetic mutation of p53 and suppression of the miR-17∼92 cluster are synthetic lethal in non-small cell lung cancer due to upregulation of vitamin D Signaling.
Cancer Res. 2015; 75(4):666-75 [PubMed] Article available free on PMC after 15/02/2016 Related Publications
Lung cancer is the leading cause of cancer-related fatalities. Recent success developing genotypically targeted therapies, with potency only in well-defined subpopulations of tumors, suggests a path to improving patient survival. We used a library of oligonucleotide inhibitors of microRNAs, a class of posttranscriptional gene regulators, to identify novel synthetic lethal interactions between miRNA inhibition and molecular mechanisms in non-small cell lung cancer (NSCLC). Two inhibitors, those for miR-92a and miR-1226*, produced a toxicity distribution across a panel of 27 cell lines that correlated with loss of p53 protein expression. Notably, depletion of p53 was sufficient to confer sensitivity to otherwise resistant telomerase-immortalized bronchial epithelial cells. We found that both miR inhibitors cause sequence-specific downregulation of the miR-17∼92 polycistron, and this downregulation was toxic only in the context of p53 loss. Mechanistic studies indicated that the selective toxicity of miR-17∼92 polycistron inactivation was the consequence of derepression of vitamin D signaling via suppression of CYP24A1, a rate-limiting enzyme in the 1α,25-dihydroxyvitamin D3 metabolic pathway. Of note, high CYP24A1 expression significantly correlated with poor patient outcome in multiple lung cancer cohorts. Our results indicate that the screening approach used in this study can identify clinically relevant synthetic lethal interactions and that vitamin D receptor agonists may show enhanced efficacy in p53-negative lung cancer patients.

Ragusa M, Statello L, Maugeri M, et al.
Specific alterations of the microRNA transcriptome and global network structure in colorectal cancer after treatment with MAPK/ERK inhibitors.
J Mol Med (Berl). 2012; 90(12):1421-38 [PubMed] Related Publications
The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway has a master control role in various cancer-related biological processes as cell growth, proliferation, differentiation, migration, and apoptosis. It also regulates many transcription factors that control microRNAs (miRNAs) and their biosynthetic machinery. To investigate on the still poorly characterised global involvement of miRNAs within the pathway, we profiled the expression of 745 miRNAs in three colorectal cancer (CRC) cell lines after blocking the pathway with three different inhibitors. This allowed the identification of two classes of post-treatment differentially expressed (DE) miRNAs: (1) common DE miRNAs in all CRC lines after treatment with a specific inhibitor (class A); (2) DE miRNAs in a single CRC line after treatment with all three inhibitors (class B). By determining the molecular targets, biological roles, network position of chosen miRNAs from class A (miR-372, miR-663b, miR-1226*) and class B (miR-92a-1*, miR-135b*, miR-720), we experimentally demonstrated that they are involved in cell proliferation, migration, apoptosis, and globally affect the regulation circuits centred on MAPK/ERK signaling. Interestingly, the levels of miR-92a-1*, miR-135b*, miR-372, miR-720 are significantly higher in biopsies from CRC patients than in normal controls; they also are significantly higher in CRC patients with mutated KRAS than in those with wild-type genotypes (Wilcoxon test, p < 0.05): the latter could be a downstream effect of ERK pathway overactivation, triggered by KRAS mutations. Finally, our functional data strongly suggest the following miRNA/target pairs: miR-92a-1*/PTEN-SOCS5; miR-135b*/LATS2; miR-372/TXNIP; miR-663b/CCND2. Altogether, these results contribute to deepen current knowledge on still uncharacterized features of MAPK/ERK pathway, pinpointing new oncomiRs in CRC and allowing their translation into clinical practice and CRC therapy.

Jin C, Rajabi H, Kufe D
miR-1226 targets expression of the mucin 1 oncoprotein and induces cell death.
Int J Oncol. 2010; 37(1):61-9 [PubMed] Article available free on PMC after 15/02/2016 Related Publications
The MUC1 oncoprotein is aberrantly overexpressed in human carcinomas and hematologic malignancies. Micro-RNAs (miRNAs) have been implicated in the suppression and induction of oncogenesis. The present studies demonstrate that the MUC1 mRNA 3' untranslated region (3'UTR) contains a highly conserved motif for binding of a novel miRNA, miR-1226, that has no known targets. The results show that miR-1226 is expressed in human breast cancer cell lines and non-malignant mammary epithelial cells. We also show that miR-1226 interacts with the MUC1 mRNA 3'UTR and that miR-1226 downregulates endogenous MUC1 protein levels. Consistent with miR-1226-induced downregulation of MUC1 expression, the results demonstrate that miR-1226 induces i) an increase in reactive oxygen species, ii) loss of the mitochondrial transmembrane potential, and iii) a decrease in cell survival. These findings indicate that expression of the MUC1 oncoprotein is downregulated by miR-1226 and that miR-1226 thereby functions as a tumor suppressor by promoting the induction of cell death.

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Cite this page: Cotterill SJ. MicroRNA miR-1226, Cancer Genetics Web: http://www.cancer-genetics.org/MIR1226.htm Accessed:

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This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
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