Let-7b-5p regulates proliferation and apoptosis in multiple myeloma by targeting IGF1R

Acta Biochim Biophys Sin (Shanghai). 2014 Nov;46(11):965-72. doi: 10.1093/abbs/gmu089. Epub 2014 Sep 30.

Abstract

Multiple myeloma (MM) is the most common cause of death from hematological malignancy worldwide, and recent studies have revealed that let-7b-5p can play an inhibitory role in tumorigenesis. However, the role of let-7b-5p in MM still remains unclear. The aim of this study was to elucidate the molecular mechanisms by which let-7b-5p acts as a tumor suppressor in MM. Here, quantitative real-time polymerase chain reaction results showed that the expression of let-7b-5p was remarkably reduced in MM tissues and MM cell lines (RPMI-8226 and U266 cells). Furthermore, over-expression of let-7b-5p significantly suppressed RPMI-8226 cell proliferation and induced S/G2 cell cycle arrest and apoptosis. Luciferase reporter assay results demonstrated that insulin-like growth factor receptor 1 (IGF1R) was negatively regulated by let-7b-5p at the post-transcriptional level. The mRNA and protein levels of IGF1R in RPMI-8226 cells were down-regulated by let-7b-5p. Furthermore, the cell phenotype altered by let-7b-5p inhibitor can be rescued by IGF1R silencing (si-IGF1R). Taken together, our results demonstrated that let-7b-5p functions as a tumor suppressor in MM, suggesting that let-7b-5p may be a potential therapeutic target for MM.

Keywords: apoptosis; let-7b-5p; multiple myeloma; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / genetics
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Receptor, IGF Type 1
  • Receptors, Somatomedin / antagonists & inhibitors
  • Receptors, Somatomedin / genetics*
  • Receptors, Somatomedin / metabolism

Substances

  • 3' Untranslated Regions
  • IGF1R protein, human
  • MicroRNAs
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Somatomedin
  • mirnlet7 microRNA, human
  • Receptor, IGF Type 1