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miR-485-5p/HSP90 axis blocks Akt1 phosphorylation to suppress osteosarcoma cell proliferation and migration via

Qing Liu1,2, Zhenting Wang1,3, Xiaohua Zhou2

  • 1Department of Spine Surgery, The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Changsha, Hunan, People's Republic of China.

Journal of Physiology and Biochemistry
|February 27, 2020
PubMed

Insights

Heat shock protein 90 (HSP90) and AKT1 are upregulated in osteosarcoma. Inhibiting HSP90 or increasing miR-485-5p suppresses tumor growth by affecting the PI3K/AKT pathway.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Osteosarcoma (OS) is a primary bone cancer characterized by dysregulated intracellular signaling pathways.
  • The PI3K/Akt signaling pathway is frequently implicated in OS pathogenesis.
  • Heat shock protein 90 (HSP90) is known to stabilize phospho-Akt, and both AKT1 and HSP90 are upregulated in OS.

Purpose of the Study:

  • To investigate the roles of AKT1, HSP90, and miR-485-5p in osteosarcoma.
  • To elucidate the molecular mechanisms underlying their involvement in OS progression.
  • To explore potential therapeutic targets for osteosarcoma treatment.

Main Methods:

  • Quantitative analysis of AKT1 and HSP90 mRNA and protein expression in OS tissues and cells.
  • Gene knockdown experiments (siRNA) for AKT1 and HSP90.
  • Gene overexpression experiments for AKT1.
  • Analysis of protein levels (ki-67, Vimentin, p21, E-cadherin) using Western blotting.
  • Cell viability, proliferation, and migration assays.
  • Luciferase reporter assays to confirm miR-485-5p targeting of AKT1 and HSP90 3'-UTRs.
  • Overexpression of miR-485-5p.

Main Results:

  • AKT1 and HSP90 expression were significantly upregulated in osteosarcoma.
  • AKT1 knockdown inhibited OS cell viability.
  • HSP90 knockdown suppressed AKT1 phosphorylation, decreased ki-67 and Vimentin, increased p21 and E-cadherin, and inhibited OS cell proliferation and migration.
  • AKT1 overexpression reversed the effects of HSP90 knockdown.
  • miR-485-5p directly targeted the 3'-UTRs of AKT1 and HSP90, inhibiting their expression.
  • miR-485-5p overexpression reduced AKT1, HSP90, and ki-67, increased E-cadherin, and inhibited OS cell proliferation and migration.

Conclusions:

  • HSP90 knockdown inhibits osteosarcoma progression by blocking AKT1 phosphorylation via the PI3K/AKT pathway.
  • miR-485-5p acts as a tumor suppressor in osteosarcoma by targeting and inhibiting both HSP90 and AKT1 expression.
  • Targeting HSP90 and modulating miR-485-5p levels represent potential therapeutic strategies for osteosarcoma.
Keywords:
AKT1HSP90Osteosarcoma (OS)PI3K/AKT signaling pathwaymiR-485-5p

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