Inhibition of miR301 enhances Akt-mediated cell proliferation by accumulation of PTEN in nucleus and its effects on cell-cycle regulatory proteins
| Autor: | Saeid Ghavami, Mayur V. Jain, Artur Cieślar-Pobuda, Wirginia Likus, Marek J. Łos, Ahmad Shareef |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
PTEN miR301 Cellbiologi Cell- och molekylärbiologi Apoptosis Breast Neoplasms Cell Cycle Proteins Biology PI3K Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Gene expression Biomarkers Tumor Tumor Cells Cultured medicine Humans Gene Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Cell Nucleus Cancer och onkologi Cell growth AKT Biochemistry and Molecular Biology PTEN Phosphohydrolase Cell Biology Cell biology MicroRNAs 030104 developmental biology medicine.anatomical_structure Oncology Cancer and Oncology 030220 oncology & carcinogenesis Immunology mTOR biology.protein Female Proto-Oncogene Proteins c-akt Nucleus Cell and Molecular Biology Biokemi och molekylärbiologi Research Paper Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.7996 |
| Popis: | Micro-RNAs (miRs) represent an innovative class of genes that act as regulators of gene expression. Recently, the aberrant expression of several miRs has been associated with different types of cancers. In this study, we show that miR301 inhibition influences PI3K-Akt pathway activity. Akt overexpression in MCF7 and MDAMB468 cells caused downregulation of miR301 expression. This effect was confirmed by co-transfection of miR301-modulators in the presence of Akt. Cells overexpressing miR301-inhibitor and Akt, exhibited increased migration and proliferation. Experimental results also confirmed PI3K, PTEN and FoxF2 as regulatory targets for miR301. Furthermore, Akt expression in conjunction with miR301-inhibitor increased nuclear accumulation of PTEN, thus preventing it from downregulating the PI3K-signalling. In summary, our data emphasize the importance of miR301 inhibition on PI3K-Akt pathway-mediated cellular functions. Hence, it opens new avenues for the development of new anti-cancer agents preferentially targeting PI3K-Akt pathway. Funding agencies: Cancerfonden [2013/391]; GeCONiI [POIG.02.03.01-24-099/13] |
| Databáze: | OpenAIRE |
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