MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma

Guangyi Zhao1, Chengkui Cai, Tongtao Yang

  • 1Department of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.

Plos One
|February 2, 2013
PubMed
Abstract

Insights

MicroRNA-221 (miR-221) promotes osteosarcoma progression and cisplatin resistance by targeting PTEN. Inhibiting miR-221 reverses these effects, suggesting miR-221 as a potential therapeutic target for osteosarcoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • MicroRNAs regulate gene expression and are implicated in cancer pathogenesis.
  • MicroRNA-221 (miR-221) is an oncogene overexpressed in various cancers.
  • The specific role of miR-221 in human osteosarcoma remains to be fully elucidated.

Purpose of the Study:

  • To investigate the effects of miR-221 on osteosarcoma.
  • To elucidate the mechanism by which miR-221 influences osteosarcoma survival, apoptosis, and cisplatin resistance.

Main Methods:

  • Real-time quantitative PCR to measure miR-221 expression in osteosarcoma cell lines and tissues.
  • Transfection of osteosarcoma cells with miR-221 mimics or inhibitors.
  • Cell viability, cell cycle, apoptosis, and cisplatin resistance assays.
  • Bioinformatic prediction, luciferase reporter assays, and Western blot to identify and validate miR-221 targets.
  • Immunohistochemistry to assess protein expression in patient samples.

Main Results:

  • miR-221 was significantly upregulated in osteosarcoma cells compared to osteoblasts.
  • Upregulation of miR-221 enhanced cell survival and cisplatin resistance while reducing apoptosis.
  • Knockdown of miR-221 inhibited cell growth and cisplatin resistance and induced apoptosis.
  • PTEN was confirmed as a direct target of miR-221.
  • miR-221-induced cisplatin resistance was abrogated by PTEN introduction or PI3K inhibition.
  • Osteosarcoma tissues showed high miR-221 expression and an inverse correlation with PTEN levels.

Conclusions:

  • Upregulation of miR-221 promotes the malignant phenotype of human osteosarcoma.
  • Knockdown of miR-221 reverses the malignant phenotype, indicating its oncogenic role.
  • miR-221 represents a potential therapeutic target for osteosarcoma treatment.

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