title: MiR-100 resensitizes docetaxel-resistant human lung adenocarcinoma cells (SPC-A1) to docetaxel by targeting Plk1.
abstract: MicroRNAs (miRNAs) expression correlates with biological characteristics of both normal cells and cancer cells, but their roles in cancer chemoresistance remain unclear. By microarray analysis, miR-100 was found significantly down-regulated in docetaxel-resistant SPC-A1/DTX cells compared with parental SPC-A1 cells. Ectopic miR-100 expression resensitized SPC-A1/DTX cells to docetaxel by suppression of cell proliferation and induction of cell arrest in G(2)/M phase and apoptosis. Knock-down of Plk1, which was a direct target of miR-100, yielded similar effects as that of ectopic miR-100 expression. The inverse correlation between miR-100 and Plk1 expression was also detected in nude mice SPC-A1/DTX tumor xenografts and clinical lung adenocarcinoma tissues and was proved to be related with the in vivo response to docetaxel. Thus, our results suggested that down-regulation of miR-100 could lead to Plk1 over-expression and eventually to docetaxel chemoresistance of human lung adenocarcinoma.
authors: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, PR China.
authors: Bing
authors: B
authors: Feng
authors: Rui
authors: R
authors: Wang
authors: Long-Bang
authors: LB
authors: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043823:Taxoids / Q000494:pharmacology*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D000077143:Docetaxel; D035683:MicroRNAs; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D043823:Taxoids; D000097869:Polo-Like Kinase 1; C544266:MIRN100 microRNA, human