title: MTDH is an oncogene in multiple myeloma, which is suppressed by Bortezomib treatment.
abstract: Metadherin (MTDH) is identified as an oncogene in multiple cancers including breast cancer, bladder cancer and endometrial cancer. However, the function of MTDH in multiple myeloma (MM) is still unexplored. In this study, we disclose that MTDH is an oncogene in MM. This is characterized by an elevation mRNA level of MTDH and chromosomal gain of MTDH locus in MM cells compared to normal samples. Moreover, MTDH expression significantly increased in MMSET translocation (MS) subgroup, one of the high-risk subgroups in MM, and was significantly correlated with MM patients' poor outcomes in Total Therapy 2 (TT2) cohort. Further knockdown of MTDH expression by shRNA in MM cells induced cell apoptosis, inhibited MM cells growth in vitro and decreased xenograft tumor formation in vivo. Interestingly, opposite to TT2, MM patients with high-MTDH expression showed favorable survival outcomes in the TT3 cohort, while Bortezomib treatment was the major difference between TT2 and TT3 cohort. Furthermore we proved that Bortezomib suppressed pre- and post-transcription levels of MTDH expression of MM cells in vitro and in vivo. Finally, our studies demonstrated that MTDH is a transcriptional gene of MMSET/NFκB /MYC signaling in MM cells, which is inhibited by Bortezomib treatment.
authors.affiliation: Department of Pathology, Nanjing Medical University, 210029, Nanjing, China.|Basic Medical College, Nanjing University of Chinese Medicine, 210046, Nanjing, China.|Department of Pathology, University of Iowa Carver College of Medicine, 52242, Iowa City, IA, USA.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Urology, Beijing Friendship Hospital, Capital Medical University, 100050, Beijing, China.|Department of Urology, University of Iowa Carver College of Medicine, 52242, Iowa City, IA, USA.
authors.forename: Lang
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Laboratory Medicine, Taizhou people's hospital, 225300, Taizhou, China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Peng
authors.affiliation: Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, 211198, China.
authors.forename: Hongbao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Pathology, Nanjing Medical University, 210029, Nanjing, China.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Basic Medical College, Nanjing University of Chinese Medicine, 210046, Nanjing, China.|Department of Internal Medicine, University of Iowa Carver College of Medicine, 52242, Iowa City, IA, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D000069286:Bortezomib / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D009857:Oncogenes; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D000069286:Bortezomib
keywords: Bortezomib; MMSET (WHSC1); metadherin (MTDH); multiple myeloma; oncogene