{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wen YY"],"funding":["NIEHS NIH HHS","NCI NIH HHS"],"pagination":["15897"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5698474"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(1)"],"pubmed_abstract":["Dysregulation of miRNAs is important in breast cancer initiation and malignant progression. Recently we showed that miR-152 downregulation is associated with breast cancer development, yet the underlying mechanism of miR-152 remains to be well elucidated. In this study, we identified β-catenin as a new direct target of miR-152. MiR-152 inhibited cell proliferation by targeting and inhibiting both β-catenin and PKM2 expression. We found that miR-152 expression sensitized the breast cancer cells to paclitaxel treatment by inhibiting β-catenin and PKM2 expression. Intriguingly, IGF-1 induced β-catenin and PKM2 expression and enhanced β-catenin and PKM2 interaction. Subsequently, IGF-1-induced β-catenin and PKM2 complex translocated into the nucleus, which in turn activated expression of miR-152. These results suggested a regulatory circuit between miR-152, β-catenin and PKM2 in breast cancer. By using human clinical specimens, we also showed that miR-152 expression levels were negatively correlated with β-catenin and PKM2 levels in breast cancer tissues. Our findings provide new insights into a mechanism of miR-152 involved in β-catenin and PKM2 inhibition which would have clinical implication for the cancer development and new treatment option in the future."],"journal":["Scientific reports"],"pubmed_title":["IGF-1-mediated PKM2/β-catenin/miR-152 regulatory circuit in breast cancer."],"pmcid":["PMC5698474"],"funding_grant_id":["R01 CA193511","R01 ES020868"],"pubmed_authors":["Wang M","Li W","Shi ZM","Jiang BH","Zhang JY","Wen YY","Ge X","Liu WT","Sun HR","Liu LZ"],"additional_accession":[]},"is_claimable":false,"name":"IGF-1-mediated PKM2/β-catenin/miR-152 regulatory circuit in breast cancer.","description":"Dysregulation of miRNAs is important in breast cancer initiation and malignant progression. Recently we showed that miR-152 downregulation is associated with breast cancer development, yet the underlying mechanism of miR-152 remains to be well elucidated. In this study, we identified β-catenin as a new direct target of miR-152. MiR-152 inhibited cell proliferation by targeting and inhibiting both β-catenin and PKM2 expression. We found that miR-152 expression sensitized the breast cancer cells to paclitaxel treatment by inhibiting β-catenin and PKM2 expression. Intriguingly, IGF-1 induced β-catenin and PKM2 expression and enhanced β-catenin and PKM2 interaction. Subsequently, IGF-1-induced β-catenin and PKM2 complex translocated into the nucleus, which in turn activated expression of miR-152. These results suggested a regulatory circuit between miR-152, β-catenin and PKM2 in breast cancer. By using human clinical specimens, we also showed that miR-152 expression levels were negatively correlated with β-catenin and PKM2 levels in breast cancer tissues. Our findings provide new insights into a mechanism of miR-152 involved in β-catenin and PKM2 inhibition which would have clinical implication for the cancer development and new treatment option in the future.","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Nov","modification":"2025-04-05T10:32:25.907Z","creation":"2019-03-27T03:02:40Z"},"accession":"S-EPMC5698474","cross_references":{"pubmed":["29162853"],"doi":["10.1038/s41598-017-15607-y"]}}