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

Author

Listed:
  • Chi Lam Au Yeung

    (The University of Texas MD Anderson Cancer Center)

  • Ngai-Na Co

    (The University of Texas MD Anderson Cancer Center)

  • Tetsushi Tsuruga

    (The University of Texas MD Anderson Cancer Center)

  • Tsz-Lun Yeung

    (The University of Texas MD Anderson Cancer Center)

  • Suet-Ying Kwan

    (The University of Texas MD Anderson Cancer Center)

  • Cecilia S. Leung

    (The University of Texas MD Anderson Cancer Center)

  • Yong Li

    (University of Louisville)

  • Edward S. Lu

    (The University of Texas MD Anderson Cancer Center)

  • Kenny Kwan

    (The University of Texas MD Anderson Cancer Center)

  • Kwong-Kwok Wong

    (The University of Texas MD Anderson Cancer Center)

  • Rosemarie Schmandt

    (The University of Texas MD Anderson Cancer Center)

  • Karen H. Lu

    (The University of Texas MD Anderson Cancer Center)

  • Samuel C. Mok

    (The University of Texas MD Anderson Cancer Center)

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.

Suggested Citation

  • 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, 2016. "Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11150
    DOI: 10.1038/ncomms11150
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    Cited by:

    1. Ao Fang & Yifan Wang & Naiyu Guan & Yanming Zuo & Lingmin Lin & Binjie Guo & Aisheng Mo & Yile Wu & Xurong Lin & Wanxiong Cai & Xiangfeng Chen & Jingjia Ye & Zeinab Abdelrahman & Xiaodan Li & Hanyu Zh, 2023. "Porous microneedle patch with sustained delivery of extracellular vesicles mitigates severe spinal cord injury," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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