PURPOSE: We identified microRNA driven mechanisms in clear cell renal cell carcinoma associated with the tumor response to the multitargeted receptor tyrosine kinase inhibitor sunitinib. MATERIALS AND METHODS: We performed screening genome-wide microRNA real-time quantitative polymerase chain reaction on 20 freshly frozen clear cell renal cell carcinoma tissue samples of patients who received sunitinib as first line targeted therapy. Nine patients with progressive disease within 6 months after initiating therapy were considered poor responders and 11 with at least 1-year progression-free survival were considered good responders. We studied microRNA-141 function in vitro by stable up-regulation of microRNA-141, quantification of target gene expression and cell viability in normoxic and hypoxic conditions. Relative expression in clinical and cell line samples was determined by real-time quantitative polymerase chain reaction. Localization of microRNA-141 and its targets was assessed by microRNA in situ hybridization and immunohistochemistry. Hypoxia induced cytotoxicity was assessed by a luminescence adenosine triphosphate detection assay. RESULTS: Compared to good responders, microRNA-141 was significantly down-regulated in tumors of poor responders to sunitinib. This seemed spatially linked to epithelial-to-mesenchymal transition in vivo. Reintroduction of microRNA-141 in vitro reversed epithelial-to-mesenchymal transition and decreased cell viability in hypoxic conditions. CONCLUSIONS: In our study microRNA-141 down-regulation driven epithelial-to-mesenchymal transition in clear cell renal cell carcinoma was linked to an unfavorable response to sunitinib therapy. Reintroduction of microRNA-141 in vitro led to epithelial-to-mesenchymal transition reversal and increased sensibility to a hypoxic environment. Future experiments should be done in vivo to see whether microRNA-141 driven reversal of epithelial-to-mesenchymal transition could affect the efficacy of sunitinib treatment.
PURPOSE: We identified microRNA driven mechanisms in clear cell renal cell carcinoma associated with the tumor response to the multitargeted receptor tyrosine kinase inhibitor sunitinib. MATERIALS AND METHODS: We performed screening genome-wide microRNA real-time quantitative polymerase chain reaction on 20 freshly frozen clear cell renal cell carcinoma tissue samples of patients who received sunitinib as first line targeted therapy. Nine patients with progressive disease within 6 months after initiating therapy were considered poor responders and 11 with at least 1-year progression-free survival were considered good responders. We studied microRNA-141 function in vitro by stable up-regulation of microRNA-141, quantification of target gene expression and cell viability in normoxic and hypoxic conditions. Relative expression in clinical and cell line samples was determined by real-time quantitative polymerase chain reaction. Localization of microRNA-141 and its targets was assessed by microRNA in situ hybridization and immunohistochemistry. Hypoxia induced cytotoxicity was assessed by a luminescence adenosine triphosphate detection assay. RESULTS: Compared to good responders, microRNA-141 was significantly down-regulated in tumors of poor responders to sunitinib. This seemed spatially linked to epithelial-to-mesenchymal transition in vivo. Reintroduction of microRNA-141 in vitro reversed epithelial-to-mesenchymal transition and decreased cell viability in hypoxic conditions. CONCLUSIONS: In our study microRNA-141 down-regulation driven epithelial-to-mesenchymal transition in clear cell renal cell carcinoma was linked to an unfavorable response to sunitinib therapy. Reintroduction of microRNA-141 in vitro led to epithelial-to-mesenchymal transition reversal and increased sensibility to a hypoxic environment. Future experiments should be done in vivo to see whether microRNA-141 driven reversal of epithelial-to-mesenchymal transition could affect the efficacy of sunitinib treatment.
Authors: Julia Kovacova; Jaroslav Juracek; Alexandr Poprach; Jindrich Kopecky; Ondrej Fiala; Marek Svoboda; Pavel Fabian; Lenka Radova; Petr Brabec; Tomas Buchler; Ondrej Slaby Journal: Cancer Genomics Proteomics Date: 2019 Sep-Oct Impact factor: 4.069
Authors: Heba W Z Khella; Henriett Butz; Qiang Ding; Fabio Rotondo; Kenneth R Evans; Peter Kupchak; Moyez Dharsee; Ashraf Latif; Maria D Pasic; Evi Lianidou; Georg A Bjarnason; George M Yousef Journal: Mol Ther Date: 2015-07-23 Impact factor: 11.454
Authors: Jesús García-Donas; Benoit Beuselinck; Lucía Inglada-Pérez; Osvaldo Graña; Patrick Schöffski; Agnieszka Wozniak; Oliver Bechter; Maria Apellániz-Ruiz; Luis Javier Leandro-García; Emilio Esteban; Daniel E Castellano; Aranzazu González Del Alba; Miguel Angel Climent; Susana Hernando; José Angel Arranz; Manuel Morente; David G Pisano; Mercedes Robledo; Cristina Rodriguez-Antona Journal: JCI Insight Date: 2016-07-07
Authors: Igor Koturbash; William H Tolleson; Lei Guo; Dianke Yu; Si Chen; Huixiao Hong; William Mattes; Baitang Ning Journal: Biomark Med Date: 2015-10-26 Impact factor: 2.851