Multiple myeloma (MM) is an incurable disease characterized by malignant plasma cell clonal expansion in the bone marrow;therefore,inhibiting the proliferation of plasma cells is an impor-tant approach to overcome the progression of MM.Quercetin (Que) is a promising flavonoid with broad-spectrum anti-tumor activity against various cancers,including MM;however,the under-lying mechanism is not yet understood.The present study aimed to reveal the gene expression profile of Que-treated MM cells and clarify its potential mechanism.The 30％ inhibitory concen-tration (IC30) of Que against MM cells was calculated,and the proliferation rate was significantly reduced after Que treatment.Next,495 dysregulated genes were identified via RNA sequencing in Que-treated MM cells.Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses indicated that the dysregulated genes were enriched in various apoptosis-related GO terms and amino acid metabolism-related pathways,qPCR validation showed that protein tyro-sine phosphatase receptor-type R (PTPRR) had the highest verified log2 FC (abs) among the top 15 dysregulated genes.Overexpression of PTPRR increased the sensitivity of MM cells against Que,significantly inhibiting their proliferation and colony formation ability;silencing of PTPRR showed the opposite results.Furthermore,bioinformatics analyses and PPI network construction of PTPRR indicated that dephosphorylation of ERK might be the potential pathway for the PTPRR-induced inhibition of MM cell proliferation.In summary,our study identified the gene expression profile in Que-treated MM cells and demonstrated that the upregulation of PTPRR was one of the important mechanisms for the Que-induced inhibition of MM cell proliferation.