title: MicroRNA 100 sensitizes luminal A breast cancer cells to paclitaxel treatment in part by targeting mTOR.
abstract: Luminal A breast cancer usually responds to hormonal therapies but does not benefit from chemotherapies, including microtubule-targeted paclitaxel. MicroRNAs could play a role in mediating this differential response. In this study, we examined the role of micro RNA 100 (miR-100) in the sensitivity of breast cancer to paclitaxel treatment. We found that while miR-100 was downregulated in both human breast cancer primary tumors and cell lines, the degree of downregulation was greater in the luminal A subtype than in other subtypes. The IC50 of paclitaxel was much higher in luminal A than in basal-like breast cancer cell lines. Ectopic miR-100 expression in the MCF-7 luminal A cell line enhanced the effect of paclitaxel on cell cycle arrest, multinucleation, and apoptosis, while knockdown of miR-100 in the MDA-MB-231 basal-like line compromised these effects. Similarly, overexpression of miR-100 enhanced the effects of paclitaxel on tumorigenesis in MCF-7 cells. Rapamycin-mediated inhibition of the mammalian target of rapamycin (mTOR), a target of miR-100, also sensitized MCF-7 cells to paclitaxel. Gene set enrichment analysis showed that genes that are part of the known paclitaxel-sensitive signature had a significant expression correlation with miR-100 in breast cancer samples. In addition, patients with lower levels of miR-100 expression had worse overall survival. These results suggest that miR-100 plays a causal role in determining the sensitivity of breast cancers to paclitaxel treatment.
authors.affiliation: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China.|Emory Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Baotong
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Liya
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Cancer Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China.|Emory Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Dong
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D017239:Paclitaxel / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C544266:MIRN100 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D017239:Paclitaxel
keywords: breast cancer; luminal A subtype; mTOR; miR-100; paclitaxel