Long non-coding RNA TUG1 sponges miR-197 to enhance cisplatin sensitivity in triple negative breast cancer - 20/09/18
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Graphical abstract |
TUG1 regulated miR-197/NLK axis and thus increasing cisplatin sensitivity of TNBC cells.
Highlights |
• | LncRNA TUG1 regulated cisplatin sensitivity in triple negative breast cancer. |
• | LncRNA TUG1 upregulated NLK expression via sponging miR-197. |
• | LncRNA TUG1 sensitized triple negative breast cancer to cisplatin via targeting miR-197/NLK. |
Abstract |
Breast cancer is the leading cause of women death worldwide. Several long non-coding RNAs (lncRNAs) have been identified as oncogenes or tumor suppressors during the progression of cancers. However, the role of taurine upregulated gene (TUG1) in mediating the chemotherapy sensitivity of triple negative breast cancer (TNBC) has not been studied yet. In TNBC patients, we observed a significant decrease of TUG1 in tumor tissues compared to the normal tissues. Similarly, TUG1 expression was significantly decreased in TNBC cell lines compared with normal breast epithelial cell line and cell lines of other subtypes of breast cancer. In MDA-MB-231 and BT549, cisplatin induced cell growth arrest was remarkably augmented by overexpression of TUG1 and was significantly reduced by TUG1 silencing. Moreover, very low concentration of cisplatin caused cell proliferation inhibition in TUG1-overexpressed-TNBC cells. In addition, we found that TUG1 negatively regulated miR-197 expression in the tested TNBC cell lines. Sponging of TUG1 to miR-197 was proved by a dual luciferase reporter assay. We further predicted and validated that nemo-like kinase (NLK), which was positively controlled by TUG1, was a target gene of miR-197. Via regulation of miR-197/NLK, TUG1 inactivated WNT signaling pathway and thus increasing chemotherapy sensitivity of TNBC cells. Analysis of TCGA database showed that higher expression of TUG1 was associated with better prognosis in breast cancer patients. Our current study drew a preliminary conclusion that TUG1 was involved in chemotherapy sensitivity in TNBC cells.
Le texte complet de cet article est disponible en PDF.Keywords : Triple negative breast cancer, TUG1, miR-197, NLK, Chemoresistance
Plan
Vol 107
P. 338-346 - novembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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