Microrna-138 increases chemo-sensitivity of glioblastoma through downregulation of survivin

Ji Young Yoo, Margaret Yeh, Yin Ying Wang, Christina Oh, Zhong Ming Zhao, Balveen Kaur, Tae Jin Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Glioblastoma (GBM) is one of the most deadly cancers and poorly responses to chemotherapies, such as temozolomide (TMZ). Dysregulation of intrinsic signaling pathways in cancer cells are often resulted by dysregulated tumor suppressive microRNAs (miRNAs). Previously, we found miR-138 as one of tumor suppressive miRNAs that were significantly down-regulated in GBM. In this study, we demonstrated that ectopic over-expression of miR-138 sensitizes GBM cells to the treatment of TMZ and increased apoptotic cell death. Mechanistically, miR-138 directly repressed the expression of Survivin, an anti-apoptotic protein, to enhance caspase-induced apoptosis upon TMZ treatment. Using an intracranial GBM xenograft mice model, we also showed that combination of miR-138 with TMZ increases survival rates of the mice compared to the control mice treated with TMZ alone. This study provides strong preclinical evidence of the therapeutic benefit from restoration of miR-138 to sensitize the GBM tumor to conventional chemotherapy.

Original languageEnglish (US)
Article number780
JournalBiomedicines
Volume9
Issue number7
DOIs
StatePublished - Jul 2021
Externally publishedYes

Keywords

  • BIRC5
  • Glioblastoma (GBM)
  • MicroRNA-138 (miR-138)
  • Survivin
  • Temozolomide (TMZ)

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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