The influence of PRL3 on the IL-6 pathway in multiple myeloma: an explorative analysis using transcriptomics and proteomics

Abstract

BACKGROUND: Multiple myeloma (MM) is an incurable malignancy of plasma cells. So far, blocking single growth factors, such as IL-6, has not led to improved patient survival in MM. We have previously published promising in vitro results from blocking PRL3, a downstream regulator of IL-6 signaling in MM cells. OBJECTIVES: Identify transcripts and proteins in the IL-6 signaling response regulated by PRL3. METHODS: The IL-6 dependent myeloma cell line INA-6 was transduced to overexpress PRL3. Transcriptional changes were identified by microarray gene expression BeadChips from Illumina. SILAC-based quantitative mass spectrometry was used to identify changes on the protein level. Lists with significantly upregulated genes and proteins were generated and sorted, and downstream analysis was performed with various bioinformatics tools. RESULTS: In total, 366 transcripts and 875 proteins were upregulated due to PRL3 overexpression. We identified 155 genes that were upregulated by IL-6, and by PRL3 on mRNA or protein level. Of these, STAT1 and JUN were identified as important upregulated transcription factors contributing to the extensive changes seen in the transcriptome and proteome due to PRL3 overexpression. CONCLUSIONS: PRL3 regulates key transcription factors in the IL-6 pathway, thus contributing to the survival, and possibly the malignant transformation, of multiple myeloma cells.