LAMP5 may promote MM progression by activating p38

Abstract

Multiple myeloma (MM) is the second most common tumor of the hematologic system. MM remains incurable at this time. In this study, we used bioinformatics analysis to find key genes in the pathogenesis of MM. We first found that Lysosome associated membrane protein 5 (LAMP5) expression was sequentially increased in healthy donors (HD), monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and newly diagnosed MM (NDMM), relapsed MM (RMM). We collected bone marrow from patients with NDMM, HD and post-treatment MM (PTMM) and performed qPCR analysis of LAMP5, and found that the expression of LAMP5 is stronger in NDMM than in HD, and decreases after treatment. Western blotting assay also found more expression of LAMP5 in NDMM than in HD. Patients with high LAMP5 expression have a higher DS (Durie-Salmon) stage and worse prognosis. We next verified the expression of LAMP5 in four MM cell lines and silenced LAMP5 expression in RPMI-8226 and AMO-1, and explored the effects of LAMP5 silencing on MM cell apoptosis and cell cycle by flow cytometry and western blotting. Knockdown of LAMP5 promoted apoptosis in MM cells, but had no effect on the cell cycle. Mechanistically, LAMP5 may exert its pro-tumor effects in MM in part through activation of p38 protein. We screened LAMP5 for the first time as a key gene for MM progression and recurrence, and found that LAMP5 may exert its pro-tumor effects in MM through activation of p38 protein.

A comparative analysis of transcriptomics of newly diagnosed multiple myeloma: exploring drug repurposing

“…Interestingly, CCND1 gene was additionally over-expressed by NDMM patients without chromosome 11 abnormalities indicating that cyclin D1 involvement in MM pathogenesis exceeds t(11;14) translocation and trisomy 11 ( Figure 1 ). Other oncogenes were DUSP4 and LAMP5 ( 35 , 56 – 58 ). Both of them were over-expressed in the NDMM group of the RNA-seq studies and one Affymetrix study.…”