LINC00461 Knockdown Enhances the Effect of Ixazomib in Multiple Myeloma Cells

Curr Cancer Drug Targets. 2023;23(8):643-652. doi: 10.2174/1568009623666230316152713.

Abstract

Background: LINC00461 has been implicated to be involved in several types of cancer while its roles in multiple myeloma remain unclear. Our study aims to investigate the roles of LINC00461 in multiple myeloma and explore its effects on ixazomib therapy.

Methods: LINC00461 and small nuclear ribonucleoprotein polypeptide (SNRP) B2 knockdown stable cell lines were constructed. Cell viability assays including MTT, cell number counting, and colony formation were performed. RNA-pull down and immunoblotting assays were conducted to determine the intramolecular interactions. qRT-PCR and western blotting were conducted to determine the levels of target genes. Kaplan-Meier analysis was used to evaluate overall survival rates.

Results: Knockdown of LINC00461 or SNRPB2 enhanced ixazomib's cytotoxicity, as well as affected its regulatory effects on cell apoptosis and cell cycle distribution. Further results showed that LINC00461 knockdown reduced the expression levels of SNRPB2 by their interactions. Additionally, a positive correlation between LINC00461 and SNRPB2 was found in patients with multiple myeloma. Low expression of SNRPB2 was associated with a high survival rate in patients with multiple myeloma.

Conclusion: Knockdown of LINC00461 enhanced the therapeutic effects of ixazomib against multiple myeloma in part by the regulation of SNRPB2.

Keywords: B2 knockdown; LINC00461; Multiple myeloma; SNRPB2; cell apoptosis; ixazomib.

MeSH terms

  • Apoptosis
  • Boron Compounds / pharmacology
  • Boron Compounds / therapeutic use
  • Cell Line, Tumor
  • Glycine / pharmacology
  • Glycine / therapeutic use
  • Humans
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / genetics

Substances

  • ixazomib
  • Boron Compounds
  • Glycine