microRNA-135b expression silences Ppm1e to provoke AMPK activation and inhibit osteoblastoma cell proliferation

Zheng-Wei Li1, Yun-Rong Zhu2, Xiao-Zhong Zhou3,4

  • 1The Center of Diagnosis and Treatment for Children's Bone Diseases, The Children's Hospital Affiliated to Soochow University, Suzhou, China.

Oncotarget
|May 3, 2017
PubMed

Insights

MicroRNA-135b-5p downregulation in osteoblastoma activates AMPK by silencing Ppm1e, inhibiting tumor cell proliferation. Restoring miR-135b-5p or silencing Ppm1e suppresses tumor growth in vivo.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • AMP-activated protein kinase (AMPK) activation shows potential for inhibiting osteoblastoma.
  • MicroRNAs play crucial roles in cellular processes and disease development.
  • Protein phosphatase Mg2+/Mn2+-dependent 1e (Ppm1e) is a phosphatase that may regulate AMPK activity.

Purpose of the Study:

  • To investigate the role of microRNA-135b-5p (miR-135b-5p) in osteoblastoma.
  • To determine if silencing Ppm1e via miR-135b-5p can activate AMPK and inhibit osteoblastoma cells.
  • To explore the therapeutic potential of targeting the miR-135b-5p/Ppm1e/AMPK axis in osteoblastoma.

Main Methods:

  • Analysis of miR-135b-5p and Ppm1e expression in human osteoblastoma tissues.
  • Forced expression of miR-135b-5p in human osteoblastoma cell lines (MG-63, U2OS).
  • Silencing of Ppm1e using short hairpin RNA (shRNA) and knockdown of AMPKα1.
  • In vivo studies using mouse xenograft models.

Main Results:

  • miR-135b-5p was downregulated in osteoblastoma tissues, correlating with Ppm1e upregulation and reduced AMPKα1 phosphorylation.
  • Forced miR-135b-5p expression or Ppm1e shRNA knockdown inhibited osteoblastoma cell proliferation by inducing AMPKα1 phosphorylation.
  • AMPKα1 inhibition abolished the anti-proliferative effects of miR-135b-5p.
  • In vivo, miR-135b-5p or Ppm1e shRNA significantly inhibited tumor growth in mice.

Conclusions:

  • miR-135b-5p acts as a tumor suppressor in osteoblastoma by targeting Ppm1e.
  • Silencing Ppm1e activates AMPK, leading to the inhibition of osteoblastoma cell proliferation.
  • The miR-135b-5p/Ppm1e/AMPK pathway represents a potential therapeutic target for osteoblastoma.

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