Gm6377 suppressed SP 2/0 xenograft tumor by down‑regulating Myc transcription

• B. Zhai ^[2] ; C. Hou ^[3] ; R. Xu ^[2] ; Y. Fang ^[3] ; N. Ma ^[1] ; C. Xing ^[3] ; X. Wang ^[4] ; H. Xiao ^[5] ; G. Chen ^[5] ; G. Han ^[3] ; R. Wang ^[2]
  1. [1] First Hospital of Jilin University

     First Hospital of Jilin University

     China

     
  2. [2] Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Institute of Brain Disorders, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, China
  3. [3] Institute of Military Cognition and Brain Sciences, #27, Taiping Road, P.O. Box 130 (3), Beijing 100850, China
  4. [4] Staidson (Beijing) Biopharmaceuticals Co., Ltd, Beijing 100176, China
  5. [5] State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Beijing 100850, China

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 22, Nº. 9, 2020, págs. 1463-1471
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Purpose Disturbed process of B-cell differentiation into plasmablasts (PBs)/plasma cells (PCs) is involved in multiple myeloma (MM). New strategies will be required to eliminate the MM cell clone for a long-term disease control. Because of its PB-like characteristics, the mus musculus myeloma SP 2/0 cell line was used in this study to search novel targets for PBs/PCs.

    Methods/patients Affymetrix microarrays and RNA-sequencing assays were used to search a novel different molecule (Gm6377) between PBs/PCs and mature B cells. Cell counting kit-8 (CCK8), flow cytometry (FACS), xenograft mouse model, and the luciferase reporter system were used to assess the effect of Gm6377 on SP 2/0 cell proliferation, cell cycle, tumor growth, and Myc promoter activation, respectively.

    Results We found that B cells expressed a high level of Gm6377 mRNA, whereas Gm6377 mRNA was decreased in PCs.

    In addition, SP 2/0 cells also expressed low levels of Gm6377 mRNA. Critically, Gm6377 overexpression suppressed SP 2/0 cell proliferation but not cell cycle. Furthermore, Gm6377 overexpression suppressed tumor progression in the SP 2/0 xenograft mouse model. Finally, we found that Gm6377 suppressed SP 2/0 cell proliferation by reducing the activation of the Myc promoter.

    Conclusions These results suggest that Gm6377 suppresses myeloma SP 2/0 cell growth by suppressing Myc. Thus, modula- tion of Gm6377 may be a potential therapeutic way to treat MM.