title: Downregulation of Foxo3 and TRIM31 by miR-551b in side population promotes cell proliferation, invasion, and drug resistance of ovarian cancer.
abstract: Ovarian cancer (OVCa) stem cells are associated with tumor growth, metastasis, and recurrence, which are driving forces behind a majority of the OVCa-related mortality. This subpopulation of cancer cells are characterized by uncontrolled proliferation, high invasiveness, and resistance against the current platinum-based therapy. Thus, targeting OVCa cancer stem cells has been focused in recent therapeutic development. Isolation and purification of cancer stem cells are, however, challenging for the lack of sensitive and specific markers. In this study, we demonstrated that miR-551b was upregulated in OVCa stem cells, by using a quantitative PCR array, correlating with the pathological grades of this malignancy. In vitro experiments indicated that miR-551b promoted the proliferation, invasion, and chemoresistance of OVCa cells and cancer stem cells. Further analysis suggested that miR-551b functioned through the suppression of Foxo3 and TRIM31, two important tumor suppressors. In support of this, our in vivo experiments using mouse xenograft models showed that inhibiting miR-551b significantly increased the susceptibility of OVCa cells to cisplatin and prolonged the survival of the host mice. In conclusion, our study suggested miR-551b as a potential biomarker for OVCa stem cells and explored its functional mechanism, providing a potential therapeutic target for future drug development.
authors.affiliation: Department of Oncologic Gynecology, Prenatal Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, Jilin, People's Republic of China.
authors.forename: Zhentong
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, The First Hospital of Jilin University, Changchun, 130021, Jilin, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Pathobiology, The Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, 130021, Jilin, People's Republic of China.
authors.forename: Yishu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Rheumatology, The First Hospital of Jilin University, Changchun, 130021, Jilin, People's Republic of China.
authors.forename: Yandong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, The First Hospital of Jilin University, Changchun, 130021, Jilin, People's Republic of China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Oncologic Gynecology, Prenatal Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, Jilin, People's Republic of China.
authors.forename: Xiaxia
authors.initials: X
authors.lastname: Man
authors.affiliation: Genetic Engineering Laboratory of People's Liberation Army, The Eleventh Institute of Academy of Military Medical Sciences of People's Liberation Army, Changchun, 130021, Jilin, People's Republic of China. wei_feng@jlu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.affiliation: Department of Oncologic Gynecology, Prenatal Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, Jilin, People's Republic of China. csrichard@163.com.|Institute of Zoonotic Disease, Jilin University, Changchun, 130021, Jilin, People's Republic of China. csrichard@163.com.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005260:Female; D000071316:Forkhead Box Protein O3 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D000070584:Tripartite Motif Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; C000595937:MIRN-551 microRNA, human; D035683:MicroRNAs; D000070584:Tripartite Motif Proteins; C534233:TRIM31 protein, human; D044767:Ubiquitin-Protein Ligases; D002945:Cisplatin
keywords: Cell invasion; Cell proliferation; Drug resistance; Ovarian cancer; Side population of cancer cells; miR-551b