Curcumin Inhibits the Proliferation, Migration, Invasion, and Apoptosis of Diffuse Large B-Cell Lymphoma Cell Line by Regulating MiR-21/VHL Axis

Yonsei Med J. 2020 Jan;61(1):20-29. doi: 10.3349/ymj.2020.61.1.20.

Abstract

Purpose: Curcumin exerts its anti-cancer effects, partly by targeting special microRNAs, in human cancers. MiR-21 is a key oncomir in carcinogenesis of multiple human cancers. Here, we aimed to further explore the mechanistic insight into the link between curcumin and miR-21 on diffuse large B-cell lymphoma (DLBCL).

Materials and methods: Quantitative real-time PCR assays were performed to assess the levels of miR-21 and Von Hippel-Lindau (VHL) mRNA. In situ hybridization assay was used for miR-21 expression visualization in lymphoma tissues. Western blot was used for determination of VHL protein, Ki-67, caspase-3, and cleaved caspase-3 levels. Dual-luciferase reporter assay and RNA immunoprecipitation assay were employed to confirm the direct target of miR-21. MTT assay, flow cytometric analysis, and transwell assay were used to evaluate cell proliferation, apoptosis, and migration and invasion capacities, respectively.

Results: Curcumin repressed the proliferation, migration, and invasion abilities and promoted apoptosis in SU-DHL-8 cells. Curcumin inhibited miR-21 expression and curcumin exerted its anti-proliferation, anti-migration, anti-invasion, and pro-apoptosis effects by miR-21 in SU-DHL-8 cells. VHL was a direct target of miR-21. Moreover, curcumin exerted its regulatory effects on SU-DHL-8 cells by VHL.

Conclusion: Curcumin exerted its anti-proliferation, anti-migration, anti-invasion, and pro-apoptosis functions, at least partly, by repressing miR-21 and regulating VHL expression in DLBCL cell line. Our findings provided a possible molecular mechanism of curcumin-mediated anti-cancer effect.

Keywords: Diffuse large B-cell lymphoma (DLBCL); Von Hippel-Lindau (VHL); curcumin; miR-21.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / ethics*
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Von Hippel-Lindau Tumor Suppressor Protein / metabolism*

Substances

  • MIRN21 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Curcumin