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Long noncoding RNA OIP5-AS1 causes cisplatin resistance in osteosarcoma through inducing the LPAATβ/PI3K/AKT/mTOR

Lei Song1, Zhigang Zhou2, Yibo Gan3

  • 1Department of Orthopedics, First Affiliated Hospital, Army Medical University, Chongqing, China.

Journal of Cellular Biochemistry
|December 15, 2018
PubMed

Insights

Long noncoding RNA OIP5-AS1 promotes cisplatin resistance in osteosarcoma by upregulating LPAATβ and activating the PI3K/AKT/mTOR pathway via sponging miR-340-5p.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Abnormal long noncoding RNA (lncRNA) expression is implicated in cancer progression and drug resistance.
  • The role of lncRNA OIP5-AS1 in osteosarcoma cisplatin resistance is currently unknown.

Purpose of the Study:

  • To investigate the function and mechanism of OIP5-AS1 in cisplatin resistance of osteosarcoma.

Main Methods:

  • Quantitative real-time PCR to assess OIP5-AS1 expression in cisplatin-resistant (CR) osteosarcoma cells.
  • In vitro and in vivo experiments involving OIP5-AS1 silencing.
  • Western blot analysis to evaluate drug resistance factors (MRP1, P-gp) and signaling pathway proteins (PI3K/AKT/mTOR).
  • RNA immunoprecipitation and luciferase reporter assays to confirm the interaction between OIP5-AS1, miR-340-5p, and LPAATβ.

Main Results:

  • OIP5-AS1 was significantly upregulated in CR osteosarcoma cells.
  • OIP5-AS1 knockdown suppressed cell growth, promoted apoptosis, and decreased cisplatin resistance.
  • OIP5-AS1 silencing reduced MRP1 and P-gp expression and inhibited the PI3K/AKT/mTOR pathway.
  • OIP5-AS1 acted as a competing endogenous RNA for miR-340-5p, regulating LPAATβ expression.
  • miR-340-5p downregulation partially reversed the effects of OIP5-AS1 knockdown on the PI3K/AKT/mTOR pathway and cisplatin resistance.

Conclusions:

  • OIP5-AS1 induces cisplatin resistance in osteosarcoma by upregulating LPAATβ and activating the PI3K/AKT/mTOR signaling pathway through sponging miR-340-5p.
  • OIP5-AS1 is a potential therapeutic target for overcoming cisplatin resistance in osteosarcoma.
Keywords:
cisplatin resistancelong noncoding RNA OIP5-AS1miR-340-5posteosarcomasignaling pathway

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