C1orf35 contributes to tumorigenesis by activating c-MYC transcription in multiple myeloma
C1orf35 contributes to tumorigenesis by activating c-MYC transcription in multiple myeloma
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DOI：
10.1038/s41388-020-1222-7
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发表时间：
2020-02-27
期刊：
影响因子：
8
通讯作者：
Hu, Jingping
中科院分区：
文献类型：
--
作者：
Luo, Sai-Qun;Xiong, De-Hui;Hu, Jingping
多发性骨髓瘤（MM）是一种临床和生物学异质性事件，约占所有血液系统恶性肿瘤的10%。1号染色体开放阅读框35 （C1orf35）是我们实验室从MM细胞系（GenBank: AY137773）中克隆并鉴定的基因，但对其功能知之甚少。在目前的研究中，我们已经证实了C1orf35是一个候选癌基因，它可以促进细胞周期从G1到s的进展，后来我们发现C1orf35可以通过调节c-MYC （v-myc髓细胞瘤病病毒癌基因同源物）的表达来影响细胞增殖，并且可以通过抑制c-MYC来挽救C1orf35的致癌特性。在此，我们发现在MM患者和MM细胞系中，C1orf35和c-MYC呈正相关。GEO数据集中MM患者共扩增基因的相关性分析显示C1orf35与c-MYC之间存在相关性，GEO数据集中不同阶段浆细胞肿瘤的表达数据显示C1orf35的表达随着疾病的进展而增加。这表明C1orf35可能在疾病进展中发挥作用。此外，C1orf35可以调节c-MYC的表达，并挽救被Act d抑制的c-MYC转录。最后，我们发现C1orf35通过结合c-MYC启动子中核酸酶超敏元件III1 （NHE III1）的i基序激活c-MYC转录。我们目前的研究不仅提高了我们对MM的发病机制和治疗前景的认识，而且还提高了其他癌症类型和疾病的认识，这些癌症和疾病是由c-MYC转录失调引起的。
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.