Quercetin inhibits the proliferation of multiple myeloma cells by upregulating PTPRR expression

Acta Biochim Biophys Sin (Shanghai). 2021 Nov 10;53(11):1505-1515. doi: 10.1093/abbs/gmab128.

Abstract

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 important 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 underlying 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 concentration (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 tyrosine 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.

Keywords: PTPRR; RNA-seq; multiple myeloma; quercetin.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Extracellular Signal-Regulated MAP Kinases / genetics*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Ontology
  • Humans
  • Metabolic Networks and Pathways / drug effects
  • Metabolic Networks and Pathways / genetics
  • Molecular Sequence Annotation
  • Plasma Cells / drug effects*
  • Plasma Cells / metabolism
  • Plasma Cells / pathology
  • Quercetin / pharmacology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 7 / antagonists & inhibitors
  • Receptor-Like Protein Tyrosine Phosphatases, Class 7 / genetics*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 7 / metabolism
  • Signal Transduction

Substances

  • Antineoplastic Agents, Phytogenic
  • RNA, Small Interfering
  • Quercetin
  • Extracellular Signal-Regulated MAP Kinases
  • PTPRR protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 7