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C1orf35 contributes to tumorigenesis by activating c-MYC transcription in multiple myeloma

Oncogene volume 39, pages 3354–3366 (2020)Cite this article

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Abstract

Multiple myeloma (MM) is a clinically and biologically heterogenous event that accounts for approximately 10% of all hematological malignancies. Chromosome 1 open reading frame 35 (C1orf35) is a gene cloned and identified in our laboratory from a MM cell line (GenBank: AY137773), but little is known about its function. In the current study, we have confirmed that C1orf35 is a candidate oncogene, and it can promote cell cycle progression from G1 to S. Later, we found that C1orf35 is able to affect the cell proliferation by modulating the expression of c-MYC (v-myc myelocytomatosis viral oncogene homolog), and the oncogenic property of C1orf35 can be rescued by c-MYC inhibition. Herein, we found positive association between C1orf35 and c-MYC in MM patients and in MM cell lines. The correlation analysis of the genes coamplified in MM patients from GEO datasets showed a correlation between C1orf35 and c-MYC, and the expression data of different stages of plasma cell neoplasm acquired from GEO datasets showed that the expression of C1orf35 increase with the progression of the disease. This indicates that C1orf35 may play a role in the disease progression. Moreover, C1orf35 can modulate c-MYC expression and rescue c-MYC transcription inhibited by Act D. Finally, we have shown that C1orf35 activates c-MYC transcription by binding to the i-motif of Nuclease hypersensitivity element III1 (NHE III1) in the c-MYC promoter. Not only does our current study advance our knowledge of the pathogenesis and therapeutic landscape of MM, but also of other cancer types and diseases that are initiated with deregulated c-MYC transcription.

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Fig. 1: Overexpression of C1orf35 promotes tumorigenesis in BALB/c nude mice.
Fig. 2: Overexpression of C1orf35 promotes cell cycle progression from G1 to S.
Fig. 3: C1orf35 displayed positive association with c-MYC in both MM patients and MM cell lines.
Fig. 4: C1orf35 affect c-MYC expression and cell proliferation in MM cells.
Fig. 5: Clorf35 can reverse the c-MYC transcription inhibited by Act D.
Fig. 6: The mechanism of C1orf35 activation of c-MYC transcription.

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Acknowledgements

This work was supported with grants from the National Natural Science Foundation of China (Nos. 81372538, 81400819, 81071947, 39880021 and 30770906).

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  1. Molecular Biology Research Center, School of Life Science, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, China

    Sai-Qun Luo, De-Hui Xiong, Jiang Li, Jia-Ming Zhang, Xiu-Fen Bu, Wei-Xin Hu & Jingping Hu

  2. Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, China

    Guangdi Li & Yali Wang

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Contributions

JH and WXH conceived and wrote the manuscript. SQL, DHX, JL, JMZ, XFB, JH, and WXH designed and performed the experiments. GL and YW performed bioinformatic analysis. SQL, JH, and WXH evaluated and analyzed the results.

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Correspondence to Wei-Xin Hu or Jingping Hu.

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Luo, SQ., Xiong, DH., Li, J. et al. C1orf35 contributes to tumorigenesis by activating c-MYC transcription in multiple myeloma. Oncogene 39, 3354–3366 (2020). https://doi.org/10.1038/s41388-020-1222-7

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