title: Inhibition of miR301 enhances Akt-mediated cell proliferation by accumulation of PTEN in nucleus and its effects on cell-cycle regulatory proteins.
abstract: 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.
authors.affiliation: Department of Clinical & Experimental Medicine, Division of Cell Biology Integrative Regenerative Medicine Center (IGEN), Linköping University, Linköping, Sweden.
authors.forename: Mayur V
authors.initials: MV
authors.lastname: Jain
authors.affiliation: Department of Clinical & Experimental Medicine, Division of Cell Biology Integrative Regenerative Medicine Center (IGEN), Linköping University, Linköping, Sweden.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Shareef
authors.affiliation: Department of Human Anatomy, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Wirginia
authors.initials: W
authors.lastname: Likus
authors.affiliation: Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Cieślar-Pobuda
authors.affiliation: Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
authors.forename: Saeid
authors.initials: S
authors.lastname: Ghavami
authors.affiliation: Department of Pathology, Pomeranian Medical University, Szczecin, Poland.|LinkoCare Life Sciences AB, Linköping, Sweden.
authors.forename: Marek J
authors.initials: MJ
authors.lastname: Łos
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C550735:MIRN301A microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Akt; PI3K; PTEN; mTOR; miR301