Abstract LB-070: The studies of tumor-associated gene C1orf35 in pathogenesis of human multiple myeloma
Authors: Wei-Xin Hu, Sai-Qun Luo, Yan Zhong, Xiu-Feng Bu, Yang Zhou
Journal: Cancer Research (2015)

Abstract Multiple myeloma (MM) is a disease characterized by the uncontrolled proliferation and accumulation of malignant plasma cells in the bone marrow. Cancer cells are characterized by a profound genetic instability resulting in a complex set of numerical and structural chromosomal abnormalities. We previously cloned a tumor-associated gene C1orf35 from MM cell line ARH-77, which located the chromosome 1q42.13. The results showed that C1orf35 could promote the transformation, cell growth and proliferation of NIH3T3 cells, as well as cell transition from phase G1 to S. C1orf35 also possessed the potentials of promoting tumor formation in animal experiments. Based on this finding, we further explored the molecular mechanism of C1orf35 gene up-regulation and its effects on pathogenesis of human MM. The expression level of C1orf35 gene in MM patients was detected by RT-PCR. The gene expression of C1orf35 in mononuclear cells of MM patients was up-regulated (68.9%), and was not detectable in normal controls. The lentivirus vector GV248/C1orf35-RNAi for interference experiments was constructed and the NIH3T3/C1orf35-RNAi cell line which stable expressed C1orf35-RNAi was set up. The expression level of C1orf35 in NIH3T3/C1orf35-RNAi cells was detected by real-time PCR and Western blotting. The results showed that the expression levels of both mRNA and protein were down-regulated and the cell proliferation was markedly decreased after interference. By detecting the c-myc expression level of NIH3T3/Clorf35-RNAi cells, we found that expression level of c-myc gene and protein all decreased. These results indicated that down-regulation of C1orf35 was followed by down-regulation of c-myc, which implied C1orf35 might play an important role in c-myc-dependent pathway. To investigate the effects of C1orf35 gene on proliferation of MM cells, we interfered and over-expressed C1orf35 gene. The results showed that the cell proliferation was obviously decreased after interference, and the cell proliferation was significantly accelerated after over-expression of C1orf35 gene. The bioinformatics analysis showed that C1orf35 protein was located in nucleus and might play an important role for transcription regulation, which may participate in the activation of some oncogenes. We detected the binding of C1orf35 protein and promoter region of proto-oncogene c-myc with chromatin immunoprecipitation assay (ChIP) and the results showed that C1orf35 protein binds promoter region of c-myc in -226 to -10 bp. This work may contribute to reveal the role of C1orf35 in MM pathogenesis. Note: This abstract was not presented at the meeting. Citation Format: Wei-Xin Hu, Sai-Qun Luo, Yan Zhong, Xiu-Feng Bu, Yang Zhou. The studies of tumor-associated gene C1orf35 in pathogenesis of human multiple myeloma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-070. doi:10.1158/1538-7445.AM2015-LB-070