Research Paper Volume 11, Issue 23 pp 11369—11381

Posttranscriptional regulation of AKT by circular RNA angiomotin- like 1 mediates chemoresistance against paclitaxel in breast cancer cells

Jian Ma 1, 2, , Ling Fang 1, , Qi Yang 1, 3, , Steven Hibberd 1, , William W. Du 1, 4, , Nan Wu 1, , Burton B. Yang 1, 4, ,

  • 1 Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada
  • 2 Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
  • 3 The First Hospital, Jilin University, Jilin, China
  • 4 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada

received: September 7, 2019 ; accepted: November 18, 2019 ; published: December 9, 2019 ;

https://doi.org/10.18632/aging.102535
How to Cite

Copyright © 2019 Ma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Chemoresistance of triple negative breast cancer against paclitaxel (PAX) is one of the major issues for the patients under chemotherapy. However, the mechanism by which the breast cancer cells are resistant to PAX remains unclear. Here, we identified a circular RNA of angiomotin-like 1 (circAMOTL1) as an important player which may be responsible for the adverse resistance against PAX in breast cancer cells. The circAMOTL1 were overexpressed in MDA-MB-231 breast cancer cells via transfection of circAMOTL1 construct. Overexpression of circAMOTL1 caused significant increase of cell viability, reduction of apoptosis, and enhancement of invasion when MDA-MB-231 cells were exposed to PAX compared to those cells with vector control. Moreover, these resistant effects could be blocked by the application of circAMOTL1 siRNA. In these circAMOTL1 overexpressing cells, we found notable increase of both phosphorylated and total AKT protein, which suggested that AKT might be the downstream factor mediating the resistant effects. Consequently, the gene and protein expression of AKT related pro-apoptotic (BAX and BAK) and anti-apoptotic (BCL-2) factors were significantly changed by circAMOTL1 as well. These results suggest circAMOTL1 may play an important role in the PAX resistance of breast cancer cells via regulation of AKT pathway, facilitation of anti-apoptotic protein and inhibition of pro-apoptotic protein. While providing a new mechanism of PAX resistance in breast cancer cells, our findings may lay groundwork for a novel therapeutic target of the breast cancer treatment in the future.

Abbreviations

DMEM: Dulbecco’s modified Eagle’s medium; FBS: fetal bovine serum; GFP: green fluorescent protein.