BACKGROUND: MicroRNAs (miRNAs) have been identified as important posttranscriptional regulators involved in various biological and pathological processes of cells, but their association with tumor chemoresistance has not been fully understood. METHODS: We detected miRNA-200b (miR-200b) expression in different lung adenocarcinoma cell lines and then focused on its roles in regulation of docetaxel chemoresistance. We also identified E2F3 as a novel target of miR-200b. RESULTS: Based on miRNA microarray data, miR-200b was identified as the most down-regulated miRNA in docetaxel-resistant SPC-A1/DTX cells compared with parental SPC-A1 cells. Ectopic miR-200b expression reversed docetaxel chemoresistance of lung adenocarcinoma cells through cell proliferation inhibition, apoptosis enhancement, and G(2) /M cell cycle arrest. In a nude mouse xenograft model, up-regulation of miR-200b significantly enhanced response of SPC-A1/DTX cells to docetaxel. Luciferase reporters containing the 3' untranslated region sequence of E2F3 messenger RNA were used to demonstrate that miR-200b could directly target E2F3. Small interfering RNA-mediated E2F3 knockdown revealed similar effects as that of ectopic miR-200b expression. Decreased miR-200b expression was also detected in tumor tissues sampled from lung adenocarcinoma patients treated with docetaxel-based chemotherapy and was proved to be correlated with high expression of E2F3, decreased sensitivity to docetaxel, and poor prognosis. CONCLUSIONS: Our results suggest that down-regulation of miR-200b could lead to E2F3 overexpression and in turn contribute to chemoresistance of lung adenocarcinoma cells to docetaxel.
BACKGROUND: MicroRNAs (miRNAs) have been identified as important posttranscriptional regulators involved in various biological and pathological processes of cells, but their association with tumor chemoresistance has not been fully understood. METHODS: We detected miRNA-200b (miR-200b) expression in different lung adenocarcinoma cell lines and then focused on its roles in regulation of docetaxel chemoresistance. We also identified E2F3 as a novel target of miR-200b. RESULTS: Based on miRNA microarray data, miR-200b was identified as the most down-regulated miRNA in docetaxel-resistant SPC-A1/DTX cells compared with parental SPC-A1 cells. Ectopic miR-200b expression reversed docetaxel chemoresistance of lung adenocarcinoma cells through cell proliferation inhibition, apoptosis enhancement, and G(2) /M cell cycle arrest. In a nude mouse xenograft model, up-regulation of miR-200b significantly enhanced response of SPC-A1/DTX cells to docetaxel. Luciferase reporters containing the 3' untranslated region sequence of E2F3 messenger RNA were used to demonstrate that miR-200b could directly target E2F3. Small interfering RNA-mediated E2F3 knockdown revealed similar effects as that of ectopic miR-200b expression. Decreased miR-200b expression was also detected in tumor tissues sampled from lung adenocarcinomapatients treated with docetaxel-based chemotherapy and was proved to be correlated with high expression of E2F3, decreased sensitivity to docetaxel, and poor prognosis. CONCLUSIONS: Our results suggest that down-regulation of miR-200b could lead to E2F3 overexpression and in turn contribute to chemoresistance of lung adenocarcinoma cells to docetaxel.
Authors: Yue Zhao; Lu Zhao; Ivan Ischenko; Qi Bao; Bettina Schwarz; Hanno Nieß; Yan Wang; Andrea Renner; Josef Mysliwietz; Karl-Walter Jauch; Peter J Nelson; Joachim W Ellwart; Christiane J Bruns; Peter Camaj Journal: Target Oncol Date: 2015-02-03 Impact factor: 4.493
Authors: Rajesha Rupaimoole; Da Yang; Rehan Akbani; Chad V Pecot; Cristina Ivan; Chunhua Lu; Sherry Wu; Hee-Dong Han; Maitri Y Shah; Cristian Rodriguez-Aguayo; Justin Bottsford-Miller; Yuexin Liu; Sang Bae Kim; Anna Unruh; Vianey Gonzalez-Villasana; Li Huang; Behrouz Zand; Myrthala Moreno-Smith; Lingegowda S Mangala; Morgan Taylor; Heather J Dalton; Vasudha Sehgal; Yunfei Wen; Yu Kang; Keith A Baggerly; Ju-Seog Lee; Prahlad T Ram; Murali K Ravoori; Vikas Kundra; Xinna Zhang; Rouba Ali-Fehmi; Ana-Maria Gonzalez-Angulo; Pierre P Massion; George A Calin; Gabriel Lopez-Berestein; Wei Zhang; Anil K Sood Journal: Nat Commun Date: 2013 Impact factor: 14.919