Locus Summary

Gene:MIR1226; microRNA 1226
Aliases: MIRN1226, mir-1226, hsa-mir-1226
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, Ensembl, GeneCard, Gene
Source:NCBIAccessed: 01 September, 2019

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 02 September 2019 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 01 September, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (3)

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)

Zhou Q, Zeng H, Ye P, et al.
Differential microRNA profiles between fulvestrant-resistant and tamoxifen-resistant human breast cancer cells.
Anticancer Drugs. 2018; 29(6):539-548 [PubMed] Related Publications
Increasing evidence has shown that the dysregulation of microRNAs (miRNAs) is associated with drug resistance. Fulvestrant and tamoxifen represent the major endocrine drugs for the treatment of breast cancer patients, and yet little is known about the biological mechanisms of acquiring resistance to fulvestrant and tamoxifen, let alone the differences between cell lines resistant to these two drugs. Exploration of the differential miRNA profiles between these two cell lines is a useful way to further clarify these resistance mechanisms. The fulvestrant-resistant cell line (MCF7-F) and the tamoxifen-resistant cell line (MCF7-T) were established from the drug-sensitive parental MCF7 cell line using a 21-day high-dose antiestrogen induction method. Differentially expressed miRNA profiles of MCF7-F and MCF7-T were detected using microarray; then, multiple bioinformatic analyses were carried out, including protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Compared with the parental MCF7 cell line, more miRNAs were found to be participating in the process of acquiring fulvestrant resistance than tamoxifen resistance. miR-4532, miR-486-5p, miR-138, miR-1228, and miR-3178 could be new targets for combating both fulvestrant resistance and tamoxifen resistance. miR-3188, miR-21, miR-149, and others may be associated with fulvestrant resistance, whereas miR-342 and miR-1226 may be associated with tamoxifen resistance in breast cancer cells. We found differential miRNA profiles between fulvestrant-resistant and tamoxifen-resistant breast cancer cells, but the definite mechanism involved in gaining resistance still needs further study.

Lindner K, Eichelmann AK, Matuszcak C, et al.
Complex Epigenetic Regulation of Chemotherapy Resistance and Biohlogy in Esophageal Squamous Cell Carcinoma via MicroRNAs.
Int J Mol Sci. 2018; 19(2) [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Resistance towards chemotherapy is a major obstacle in the treatment of esophageal squamous cell carcinoma (ESCC). We investigated the role of specific microRNAs in chemotherapy resistance and tumor biology.
METHODS: We selected three microRNAs from characteristic microRNA signatures of resistant ESCC (hsa-miR-125a-5p, hsa-miR-130a-3p, hsa-miR-1226-3p), and hsa-miR-148a-3p. Effects on chemotherapy, adhesion, migration, apoptosis and cell cycle were assessed in six ESCC cell lines. Target analyses were performed using Western blotting and luciferase techniques.
RESULTS: MiR-130a-3p sensitized cells towards cisplatin in 100% of cell lines, miR-148a-3p in 83%, miR-125a-5p in 67%, miR-1226-3p in 50% (
CONCLUSION: Our data present strong evidence that specific microRNA signatures are responsible for drug resistance and aggressiveness of ESCC. Final functional readout of these complex processes appears to be more important than single microRNA-target interactions.

Zheng L, Li X, Gu Y, et al.
The 3'UTR of the pseudogene CYP4Z2P promotes tumor angiogenesis in breast cancer by acting as a ceRNA for CYP4Z1.
Breast Cancer Res Treat. 2015; 150(1):105-18 [PubMed] Related Publications
Pseudogenes are now known to regulate their protein-coding counterparts. Additionally, disturbances of 3'UTRs could increase the risk of cancer susceptibility by acting as modulators of gene expression. The aim of this study was to investigate the roles of the pseudogene CYP4Z2P-3'UTR and functional gene CYP4Z1-3'UTR in breast cancer angiogenesis process. The levels of CYP4Z2P- and CYP4Z1-3'UTR and miRNA of interests were measured in 22 cancerous tissues paired with non-cancerous samples by qRT-PCR. The effects of CYP4Z2P- and CYP4Z1-3'UTR were studied by overexpression and RNA interference approaches in vitro and ex vivo. Insights of the mechanism of competitive endogenous RNAs were gained from bioinformatic analysis, luciferase assays, and western blot. The positive CYP4Z2P/CYP4Z1 interaction and negative interaction between predicted miRNAs and CYP4Z2P or CYP4Z1 were identified via qRT-PCR assay and bivariate correlation analysis. CYP4Z2P- and CYP4Z1-3'UTR share several miRNA-binding sites, including miR-211, miR-125a-3p, miR-197, miR-1226, and miR-204. The CYP4Z2P- and CYP4Z1-3'UTRs arrest the interference caused by of these miRNAs, resulting in increased translation of CYP4Z1. Moreover, ectopic expression of the CYP4Z2P- and CYP4Z1-3'UTRs exhibit tumor angiogenesis-promoting properties in breast cancer collectively by inducing the phosphorylation of ERK1/2 and PI3K/Akt. Co-transfection with Dicer siRNA reversed the CYP4Z2P 3'UTR-mediated changes. Additionally, PI3K or ERK inhibitors reversed CYP4Z2P- and CYP4Z1-3'UTR-mediated changes in VEGF-A expression. Increased CYP4Z2P- and CYP4Z1-3'UTR expression promotes tumor angiogenesis in breast cancer partly via miRNA-dependent activation of PI3K/Akt and ERK1/2. The CYP4Z2P- and CYP4Z1-3'UTRs could thus be used as combinatorial miRNA inhibitors.

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] Free Access to Full Article 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] Free Access to Full Article 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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