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miR-451a targeting IL-6R activates JAK2/STAT3 pathway, thus regulates proliferation and apoptosis of multiple myeloma

Lingling Xu1, Yuning Yao2, Ting Lu1

  • 1Department of Hematology, The Second Affiliated Hospital of Qiqihar Medical College, China.

Journal of Musculoskeletal & Neuronal Interactions
|June 1, 2022
PubMed
Abstract

Insights

MicroRNA-451a (miR-451a) targets interleukin-6 receptor (IL-6R) in multiple myeloma (MM). Upregulating miR-451a inhibits MM cell proliferation and promotes apoptosis via the JAK2/STAT3 pathway.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Multiple myeloma (MM) is a hematological malignancy characterized by uncontrolled proliferation of plasma cells.
  • Dysregulation of microRNAs (miRNAs) and cytokines like interleukin-6 (IL-6) plays a crucial role in MM pathogenesis.
  • Understanding the molecular mechanisms governing MM cell growth and survival is essential for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of miR-451a in regulating multiple myeloma (MM) cell proliferation and apoptosis.
  • To elucidate the mechanism by which miR-451a affects MM cells, specifically its targeting of interleukin-6 receptor (IL-6R) and the JAK2/STAT3 signaling pathway.

Main Methods:

  • Quantitative real-time PCR (RT-qPCR) to measure miR-451a and IL-6R expression in MM patients.
  • Cell culture and transfection of U266 MM cells with miR-451a mimics.
  • Cell proliferation assays (CCK-8) and apoptosis analysis (flow cytometry).
  • Bioinformatic prediction (TargetScan) and dual-luciferase reporter assay to confirm miR-451a targeting of IL-6R.
  • Western blotting to assess JAK2/STAT3 pathway activation.

Main Results:

  • Patients with MM exhibited lower plasma miR-451a levels and higher IL-6R expression compared to healthy controls.
  • miR-451a directly targets and negatively regulates IL-6R expression.
  • Overexpression of miR-451a significantly inhibited U266 cell proliferation and induced apoptosis.
  • IL-6R stimulation promoted U266 cell proliferation and suppressed apoptosis.
  • Upregulation of miR-451a suppressed JAK2/STAT3 pathway activation, while its downregulation promoted pathway activation.

Conclusions:

  • miR-451a plays a tumor-suppressive role in multiple myeloma by targeting IL-6R.
  • The miR-451a/IL-6R axis regulates MM cell proliferation and apoptosis through the JAK2/STAT3 signaling pathway.
  • Targeting miR-451a or its downstream effectors may represent a potential therapeutic strategy for multiple myeloma.
Keywords:
ApoptosisIL-6RMultiple MyelomaProliferationmiR-451a

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