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Long Noncoding RNA GAS5 Suppresses Cell Growth and Epithelial-Mesenchymal Transition in Osteosarcoma by Regulating

Kaishan Ye1, Shuanke Wang1, Haihong Zhang1

  • 1Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, 730030, China.

Journal of Cellular Biochemistry
|May 19, 2017
PubMed

Insights

Long noncoding RNA GAS5 acts as a tumor suppressor in osteosarcoma. It inhibits cancer cell growth and migration by regulating the miR-221/ARHI pathway, offering potential therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Dysregulated long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are implicated in human cancers.
  • The lncRNA growth arrest-specific 5 (GAS5) is a known tumor suppressor, but its role in osteosarcoma remains unclear.

Purpose of the Study:

  • To investigate the function and mechanism of GAS5 in osteosarcoma tumorigenesis.
  • To explore the relationship between GAS5, miR-221, and ARHI in osteosarcoma.

Main Methods:

  • Real-time PCR (RT-qPCR) to determine expression levels of GAS5, miR-221, and ARHI.
  • In vitro assays (MTT, Transwell) and Western blot to assess cell proliferation, migration, and epithelial-mesenchymal transition (EMT).
  • Dual-luciferase reporter assay, RNA immunoprecipitation, and xenograft models to elucidate the regulatory mechanism.

Main Results:

  • GAS5 and ARHI expression were significantly decreased, while miR-221 was upregulated in osteosarcoma tissues and cells.
  • GAS5 overexpression suppressed osteosarcoma cell proliferation, migration, and EMT.
  • GAS5 directly targets miR-221, reducing its expression and increasing ARHI levels, thereby inhibiting tumor growth in vivo.

Conclusions:

  • lncRNA GAS5 functions as a competing endogenous RNA (ceRNA) for miR-221 in osteosarcoma.
  • GAS5 suppresses osteosarcoma cell growth and EMT by regulating the miR-221/ARHI pathway.
  • GAS5 represents a potential therapeutic target for osteosarcoma treatment.
Keywords:
APLASIA RAS HOMOLOGUE MEMBER IGROWTH ARREST-SPECIFIC 5LONG NONCODING RNAOSTEOSARCOMAmiR-221

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