title: miR-29a suppresses MCF-7 cell growth by downregulating tumor necrosis factor receptor 1.
abstract: Tumor necrosis factor receptor 1 is the main receptor mediating many tumor necrosis factor-alpha-induced cellular events. Some studies have shown that tumor necrosis factor receptor 1 promotes tumorigenesis by activating nuclear factor-kappa B signaling pathway, while other studies have confirmed that tumor necrosis factor receptor 1 plays an inhibitory role in tumors growth by inducing apoptosis in breast cancer. Therefore, the function of tumor necrosis factor receptor 1 in breast cancer requires clarification. In this study, we first found that tumor necrosis factor receptor 1 was significantly increased in human breast cancer tissues and cell lines, and knockdown of tumor necrosis factor receptor 1 by small interfering RNA inhibited cell proliferation by arresting the cell cycle and inducing apoptosis. In addition, miR-29a was predicted as a regulator of tumor necrosis factor receptor 1 by TargetScan and was shown to be inversely correlated with tumor necrosis factor receptor 1 expression in human breast cancer tissues and cell lines. Luciferase reporter assay further confirmed that miR-29a negatively regulated tumor necrosis factor receptor 1 expression by binding to the 3' untranslated region. In our functional study, miR-29a overexpression remarkably suppressed cell proliferation and colony formation, arrested the cell cycle, and induced apoptosis in MCF-7 cell. Furthermore, in combination with tumor necrosis factor receptor 1 transfection, miR-29a significantly reversed the oncogenic role caused by tumor necrosis factor receptor 1 in MCF-7 cell. In addition, we demonstrated that miR-29a suppressed MCF-7 cell growth by inactivating the nuclear factor-kappa B signaling pathway and by decreasing cyclinD1 and Bcl-2/Bax protein levels. Taken together, our results suggest that miR-29a is an important regulator of tumor necrosis factor receptor 1 expression in breast cancer and functions as a tumor suppressor by targeting tumor necrosis factor receptor 1 to influence the growth of MCF-7 cell.
authors.affiliation: 1 Department of Ultrasound, The Affiliated Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, China.
authors.forename: Yiling
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: 2 Department of Prevention and Health Statistics, Mudanjiang Medical University, Mudanjiang, China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Yang
authors.affiliation: 3 Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang, China.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Li
authors.affiliation: 4 Department of Pathology, Tumor Hospital of Mudanjiang, Mudanjiang, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Xu
authors.affiliation: 3 Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: 5 Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Lifei
authors.initials: L
authors.lastname: Chen
authors.affiliation: 3 Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang, China.
authors.forename: Yancui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 3 Key Laboratory of Tumor Prevention and Treatment (Heilongjiang Higher Education Institutions), Mudanjiang Medical University, Mudanjiang, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D047888:Receptors, Tumor Necrosis Factor, Type I
keywords: MCF-7 cell; Tumor necrosis factor receptor 1; miR-29a