Long non-coding RNA ANGPTL1-3 promotes multiple myeloma bortezomib resistance by sponging miR-30a-3p to activate c-Maf expression

Biochem Biophys Res Commun. 2019 Jul 5;514(4):1140-1146. doi: 10.1016/j.bbrc.2019.05.078. Epub 2019 May 15.

Abstract

Multiple Myeloma (MM) is a malignant hematological disease characterized by monoclonal proliferation of plasma cells in the bone marrow. In recent years, the widespread use of new drugs based on bortezomib (Btz) has significantly improved the remission rate of MM patients. However, drug resistance and disease relapse occur within a few years and MM is still considered to be an incurable disease. The amplification of the long arm of chromosome 1 is one of the most common genetic abnormalities in MM patients. Here, we found that long non-coding RNA ANGPTL1-3 which located in 1q region was overexpressed in MM. Lnc-ANGPTL1-3 expression was correlated with MM International Staging System (ISS) and overall survival. Notably, knockdown of lnc-ANGPTL1-3 increased Btz sensitivity of MM cells. Following exploration revealed that lnc-ANGPTL1-3 competitively interacted with miR-30a-3p to c-Maf, a transcription factor which was reported to be associated with Btz resistance. Taken together, our findings demonstrate that lnc-ANGPTL1-3/miR-30a-3p/c-Maf axis plays a critical role in MM Btz resistance.

Keywords: Bortezomib; Lnc-ANGPTL1-3; Multiple myeloma; c-Maf; miR-30a-3p.

MeSH terms

  • Angiopoietin-Like Protein 1
  • Angiopoietin-like Proteins / deficiency
  • Angiopoietin-like Proteins / metabolism*
  • Animals
  • Bortezomib / pharmacology*
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • Mice
  • Mice, Knockout
  • MicroRNAs / metabolism*
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Proto-Oncogene Proteins c-maf / genetics*
  • Proto-Oncogene Proteins c-maf / metabolism
  • RNA, Long Noncoding / metabolism*
  • Tumor Cells, Cultured

Substances

  • ANGPTL1 protein, human
  • Angiopoietin-Like Protein 1
  • Angiopoietin-like Proteins
  • MIRN30b microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-maf
  • RNA, Long Noncoding
  • Bortezomib