Research Papers:

MTDH is an oncogene in multiple myeloma, which is suppressed by Bortezomib treatment

Chunyan Gu _, Lang Feng, Hailin Peng, Hongbao Yang, Zhenqing Feng and Ye Yang

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Oncotarget. 2016; 7:4559-4569. https://doi.org/10.18632/oncotarget.6610

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Chunyan Gu1,2,4,*, Lang Feng3,5,*, Hailin Peng7,*, Hongbao Yang8, Zhenqing Feng1, Ye Yang2,6

1Department of Pathology, Nanjing Medical University, 210029, Nanjing, China

2Basic Medical College, Nanjing University of Chinese Medicine, 210046, Nanjing, China

3Department of Urology, Beijing Friendship Hospital, Capital Medical University, 100050, Beijing, China

4Department of Pathology, University of Iowa Carver College of Medicine, 52242, Iowa City, IA, USA

5Department of Urology, University of Iowa Carver College of Medicine, 52242, Iowa City, IA, USA

6Department of Internal Medicine, University of Iowa Carver College of Medicine, 52242, Iowa City, IA, USA

7Department of Laboratory Medicine, Taizhou people's hospital, 225300, Taizhou, China

8Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, 211198, China

*These authors have contributed equally to this work

Correspondence to:

Feng Zhenqing, e-mail: [email protected]

Ye Yang, e-mail: [email protected]

Keywords: multiple myeloma, metadherin (MTDH), oncogene, Bortezomib, MMSET (WHSC1)

Received: September 13, 2015     Accepted: November 26, 2015     Published: December 14, 2015


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.

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