Long noncoding RNA OIP5-AS1 mediates resistance to doxorubicin by regulating miR-137-3p/PTN axis in osteosarcoma

Biomed Pharmacother. 2020 Aug:128:110201. doi: 10.1016/j.biopha.2020.110201. Epub 2020 May 24.

Abstract

Opa-interacting protein 5 antisense RNA1 (OIP5-AS1) has been demonstrated to facilitate proliferation, metastasis and resistance to treatments in various types of cancers. Nevertheless, the exact mechanisms underlying the roles of OIP5-AS1 in osteosarcoma(OS) drug resistance have not yet been clearly elucidated. Therefore, we sought to investigate the functional involvement of OIP5-AS1 in osteosarcoma. Our results indicated that OIP5-AS1 was dramatically up-regulated in osteosarcoma drug-resistant tissues and cells in comparison with drug-sensitive tissues and cells. Also, the knockdown of OIP5-AS1 was found to have decreased doxorubicin resistance of OS cells. Further analyses revealed that OIP5-AS1 operated as a competitor for endogenous RNA of miR-137-3p as well as regulated pleiotrophin(PTN) expression, which has been reported to be an oncogene in OS in previous research. Furthermore, the loss of miR-137-3p or alternatively, the gain of PTN, both resulted in the abolishment of the inhibitory role of OIP5-AS1 silencing the proliferative activity. Our analyses indicated and helped to determine the role of OIP5-AS1 in contributing to tumorigenesis of osteosarcoma via the miR-137-3p/PTN axis and, therefore outlining its potential for use as a therapeutic target against this cancer.

Keywords: Chemoresistance; Osteosarcoma; Pleiotrophin; lncRNAOIP5-AS1; miR-137-3p.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Apoptosis / drug effects
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antibiotics, Antineoplastic
  • Carrier Proteins
  • Cytokines
  • MIRN137 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long noncoding RNA OIP5, human
  • pleiotrophin
  • Doxorubicin