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

Abstract

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.

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Data availability

The datasets generated and/or analyzed during the current study are available in the ArrayExpress repository, https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB - 7106, 7109, 7110, 7112, and 7139.

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Author information

Correspondence to G. Han or R. Wang.

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All procedures performed in studies involving human participants and animals were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Cite this article

Zhai, B., Hou, C., Xu, R. et al. Gm6377 suppressed SP 2/0 xenograft tumor by down-regulating Myc transcription. Clin Transl Oncol (2020) doi:10.1007/s12094-019-02280-y

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Keywords

  • Gm6377
  • Myc
  • B Cells
  • Plasma cells
  • Multiple myeloma