title: MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells.
abstract: MicroRNA-101 has been implicated as a tumor suppressor miRNA in human tumors. However, its potential functional impact and the underlying mechanisms in endometrial cancer progression have not been determined. Here, we report that in aggressive endometrial cancer cells, re-expression of microRNA-101 leads to inhibition of cell proliferation and induction of apoptosis and senescence. Ectopic overexpression of microRNA-101 attenuates the epithelial-mesenchymal transition-associated cancer cell migration and invasion, abrogates the sphere-forming capacity and enhances chemosensitivity to paclitaxel. Algorithm and microarray-based strategies identifies potential microRNA-101 targets. Among these, we validated EZH2, MCL-1 and FOS as direct targets of miR-101 and silencing of these genes mimics the tumor suppressive effects observed on promoting microRNA-101 function. Importantly, further results suggest an inverse correlation between low miR-101 and high EZH2, MCL-1 and FOS expression in EC specimens. We conclude that, as a crucial tumor suppressor, microRNA-101 suppresses cell proliferation, invasiveness and self-renewal in aggressive endometrial cancer cells via modulating multiple critical oncogenes. The microRNA-101-EZH2/MCL-1/FOS axis is a potential therapeutic target for endometrial cancer.
authors.affiliation: Department of Gynecology, Hokkaido University, Sapporo, Japan; These authors contributed equally to this work.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Konno
authors.affiliation: Department of Women's Health Educational System, Hokkaido University, Sapporo, Japan; These authors contributed equally to this work.
authors.forename: Peixin
authors.initials: P
authors.lastname: Dong
authors.affiliation: Department of Gynecology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China; These authors contributed equally to this work.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Obstetrics and Gynecology, Tohoku University, Sendai, Japan; These authors contributed equally to this work.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Suzuki
authors.affiliation: Department of Pathology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Pathology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Muyan
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Gynecology, Hokkaido University, Sapporo, Japan.
authors.forename: Hidemichi
authors.initials: H
authors.lastname: Watari
authors.affiliation: Department of Gynecology, Hokkaido University, Sapporo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mitamura
authors.affiliation: Department of Gynecology, Hokkaido University, Sapporo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Hosaka
authors.affiliation: Department of Women's Health Educational System, Hokkaido University, Sapporo, Japan.
authors.forename: Sharon J B
authors.initials: SJ
authors.lastname: Hanley
authors.affiliation: Department of Gynecology, Hokkaido University, Sapporo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Kudo
authors.affiliation: Department of Gynecology, Hokkaido University, Sapporo, Japan; Department of Women's Health Educational System, Hokkaido University, Sapporo, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sakuragi
mesh_terms: D048708:Cell Growth Processes / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D016761:Oncogene Proteins v-fos / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C579095:MCL1 protein, human; C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016761:Oncogene Proteins v-fos; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2