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

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…

• UD
  U.S. Department of Defense

  Awards: U54 CA151668, W81XWH, W81XWH-13
• UD
  U.S. Department of Health and Human Services

  Award: P30 CA016672
• OC
  Ovarian Cancer Research Fund
• MK
  Mary K. Chapman Foundation
• CP
  Cancer Prevention and Research Institute of Texas

  Awards: RP100094, P30 CA016672, CA016672
• CA
  Chinese Academy of Agricultural Sciences
• NI
  National Institutes of Health

  Awards: P50 CA083639, CA083639, CA016672, U54 CA151668, W81XWH, P30 CA016672
• UO
  University of Texas MD Anderson Cancer Center

  Awards: CA016672, P30 CA016672