Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA236526 | ENA |
REPOSITORIES: ENA
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Project description:Annexin 1 (ANXA1), an endogenous anti-inflammatory protein which modulates cellular processes such as proliferation, differentiation and apoptosis has been implicated in cancer initiation and progression. ANXA1 was previously shown to be regulated by hsa-miR-196a and promoted cell proliferation and anchorarge-dependent growth and suppressed apoptosis. However, whether ANXA1 itself regulates miRNA expression is unknown. Therefore, in this study, we investigated the regulation of miRNA by ANXA1 in breast cancer cells. Using microarray technology, 12 miRNAs were found to be significantly and consistently downregulated in MCF-7 cells (MCF-V5) overexpressing ANXA1 overexpressing MCF-7 cells (MCF-V5). Hsa-miR-26b* and hsa-miR-562 were chosen for further investigation.The data suggest that miR-26b* and miR-562 may play a role in ANXA1-induced migration and possibly angiogenesis by targeting NFKB and point towards a potential therapeutic target for breast cancer. Breast cancer MCF-7 cells (MCF-V5) overexpressing ANXA1 were cultured for RNA extraction and hybridization on Affymetrix miRNA microarrays. These were compared against the control, which were MCF-7 cells (MCF-EV) carrying an empty expression vector. Expression analyses were carried out in triplicates
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Project description:Annexin 1 (ANXA1), an endogenous anti-inflammatory protein which modulates cellular processes such as proliferation, differentiation and apoptosis has been implicated in cancer initiation and progression. ANXA1 was previously shown to be regulated by hsa-miR-196a and promoted cell proliferation and anchorarge-dependent growth and suppressed apoptosis. However, whether ANXA1 itself regulates miRNA expression is unknown. Therefore, in this study, we investigated the regulation of miRNA by ANXA1 in breast cancer cells. Using microarray technology, 12 miRNAs were found to be significantly and consistently downregulated in MCF-7 cells (MCF-V5) overexpressing ANXA1 overexpressing MCF-7 cells (MCF-V5). Hsa-miR-26b* and hsa-miR-562 were chosen for further investigation.The data suggest that miR-26b* and miR-562 may play a role in ANXA1-induced migration and possibly angiogenesis by targeting NFKB and point towards a potential therapeutic target for breast cancer.
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Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes Sequence library of miRNAs from a single sample of human foetal mesenchymal stem cells. Results tested and confirmed by northern blotting. Please note that only raw data files are available for the embryonic and neual samples and thus, directly submitted to SRA (SRX547311, SRX548700, respectively under SRP042115/PRJNA247767)
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