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MicroRNA‑466 inhibits cell proliferation and invasion in osteosarcoma by directly targeting insulin receptor

Yongning Sun1, Jingzhen Zhou2, Lina Shi1

  • 1Department of Clinical Laboratory, Ningbo No. 6 Hospital, Ningbo, Zhejiang 315040, P.R. China.

Molecular Medicine Reports
|March 1, 2019
PubMed

Insights

MicroRNA-466 (miR-466) is downregulated in osteosarcoma (OS), inhibiting cancer progression. Overexpressing miR-466 suppresses tumor growth and invasion by targeting insulin receptor substrate 1 (IRS1).

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) are crucial regulators of gene expression frequently dysregulated in human cancers.
  • Aberrant miRNA expression is implicated in the initiation and progression of osteosarcoma (OS).
  • The specific role of microRNA-466 (miR-466) in OS pathogenesis was previously unclear.

Purpose of the Study:

  • To investigate the expression and function of miR-466 in osteosarcoma.
  • To identify the molecular targets of miR-466 in OS.
  • To evaluate the therapeutic potential of miR-466 in OS treatment.

Main Methods:

  • Quantitative real-time PCR to assess miR-466 expression in OS tissues and cell lines.
  • In vitro assays (proliferation, invasion) to evaluate the functional role of miR-466.
  • Bioinformatics analysis and luciferase reporter assays to confirm direct targeting of IRS1 by miR-466.
  • Western blotting and immunohistochemistry to analyze IRS1 protein levels.

Main Results:

  • miR-466 expression was significantly downregulated in OS tissues and cell lines compared to normal controls.
  • Overexpression of miR-466 inhibited OS cell proliferation and invasion.
  • miR-466 directly targets the 3'-untranslated region of the insulin receptor substrate 1 (IRS1) gene.
  • IRS1 expression was upregulated in OS tissues and inversely correlated with miR-466 levels.
  • IRS1 overexpression partially rescued the inhibitory effects of miR-466 on OS cell progression.

Conclusions:

  • miR-466 acts as a tumor suppressor in osteosarcoma by downregulating IRS1.
  • The miR-466/IRS1 axis plays a significant role in OS progression.
  • miR-466 represents a potential novel therapeutic target for osteosarcoma treatment.

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