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

Clin Transl Oncol. 2020 Sep;22(9):1463-1471. doi: 10.1007/s12094-019-02280-y. Epub 2020 Jan 16.


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, modulation of Gm6377 may be a potential therapeutic way to treat MM.

Keywords: B Cells; Gm6377; Multiple myeloma; Myc; Plasma cells.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Down-Regulation
  • Heterografts
  • Mice
  • Mice, Inbred C57BL
  • Multiple Myeloma / genetics
  • Multiple Myeloma / metabolism*
  • Multiple Myeloma / pathology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger