1. Posttranscriptional regulation of AKT by circular RNA angiomotin- like 1 mediates chemoresistance against paclitaxel in breast cancer cells
- Author
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Jian Ma, Nan Wu, Qi Yang, Burton B. Yang, William W. Du, Ling Fang, and Steven Hibberd
- Subjects
Aging ,Paclitaxel ,Cell Survival ,Breast Neoplasms ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,circAMOTL1 ,Viability assay ,RNA Processing, Post-Transcriptional ,skin and connective tissue diseases ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Triple-negative breast cancer ,030304 developmental biology ,0303 health sciences ,AKT ,chemoresistance ,circular RNA ,RNA, Circular ,Cell Biology ,Transfection ,medicine.disease ,Angiomotin ,3. Good health ,Gene Expression Regulation, Neoplastic ,Drug Resistance, Neoplasm ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer research ,Female ,PAX ,Proto-Oncogene Proteins c-akt ,Research Paper - 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.
- Published
- 2019