Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1

Chi Lam Au Yeung, Ngai Na Co, Tetsushi Tsuruga, Tsz Lun Yeung, Suet Ying Kwan, Cecilia S. Leung, Yong Li, Edward S. Lu, Kenny Kwan, Kwong Kwok Wong, Rosemarie Schmandt, Karen H. Lu, Samuel C. Mok

Research output: Contribution to journalArticlepeer-review

392 Scopus citations

Abstract

Advanced ovarian cancer usually spreads to the visceral adipose tissue of the omentum. However, the omental stromal cell-derived molecular determinants that modulate ovarian cancer growth have not been characterized. Here, using next-generation sequencing technology, we identify significantly higher levels of microRNA-21 (miR21) isomiRNAs in exosomes and tissue lysates isolated from cancer-associated adipocytes (CAAs) and fibroblasts (CAFs) than in those from ovarian cancer cells. Functional studies reveal that miR21 is transferred from CAAs or CAFs to the cancer cells, where it suppresses ovarian cancer apoptosis and confers chemoresistance by binding to its direct novel target, APAF1. These data suggest that the malignant phenotype of metastatic ovarian cancer cells can be altered by miR21 delivered by exosomes derived from neighbouring stromal cells in the omental tumour microenvironment, and that inhibiting the transfer of stromal-derived miR21 is an alternative modality in the treatment of metastatic and recurrent ovarian cancer.

Original languageEnglish (US)
Article number11150
JournalNature communications
Volume7
DOIs
StatePublished - Mar 29 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

MD Anderson CCSG core facilities

  • Advanced Technology Genomics Core
  • High Resolution Electron Microscopy Facility
  • Research Animal Support Facility
  • Small Animal Imaging Facility
  • Cytogenetics and Cell Authentication Core

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