FOXO3a‐dependent Parkin regulates the development of gastric cancer by targeting ATP‐binding cassette transporter E1
- 10 September 2020
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 236 (4), 2740-2755
- https://doi.org/10.1002/jcp.30040
Abstract
Gastric cancer (GC) is one of the most common malignant tumors in China and the third leading cause of cancer‐related death. Parkin has been shown to be a tumor suppressor in a variety of malignancies, including GC. However, the mechanism of Parkin in GC remains unclear. In this study, the low expression of Parkin in GC cells and patient tumor tissues was observed, and Parkin inhibited proliferation and migration of GC cells. Additionally, doxorubicin (DOX) upregulated the expression of Parkin and promoted its anticancer effect. Forkhead box O3 (FOXO3a) is a crucial transcription factor that involves in the regulation of cancer cell proliferation, apoptosis, and metabolism. Here, we found that FOXO3a inhibits cell proliferation, migration, and promotes apoptosis in GC by regulating Parkin expression at the transcriptional level. In addition, Parkin inhibited cell proliferation, migration, and promoted apoptosis by inhibiting ATP‐binding box protein E1 (ABCE1) expression. In summary, our results demonstrated a new regulatory axis of FOXO3a–Parkin–ABCE1 that modulated GC cell proliferation, migration, and apoptosis, and it can serve as a potential therapeutic target in GC.Funding Information
- National Outstanding Youth Science Fund Project of National Natural Science Foundation of China (81802822)
This publication has 58 references indexed in Scilit:
- Deregulation of FoxO3a accelerates prostate cancer progression in TRAMP miceThe Prostate, 2013
- PARK2 and PACRG are commonly downregulated in clear‐cell renal cell carcinoma and are associated with aggressive disease and poor clinical outcomeGenes, Chromosomes and Cancer, 2012
- Cardiac Hypertrophy Is Positively Regulated by MicroRNA miR-23aOnline Journal of Public Health Informatics, 2012
- Unregulated miR-96 Induces Cell Proliferation in Human Breast Cancer by Downregulating Transcriptional Factor FOXO3aPLOS ONE, 2010
- FOXO3a Regulates Glycolysis via Transcriptional Control of Tumor Suppressor TSC1Online Journal of Public Health Informatics, 2010
- Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron lossNature Neuroscience, 2009
- FOXO3a-dependent regulation of Pink1 (Park6) mediates survival signaling in response to cytokine deprivationProceedings of the National Academy of Sciences of the United States of America, 2009
- Forkhead box transcription factor FOXO3a suppresses estrogen-dependent breast cancer cell proliferation and tumorigenesisBreast Cancer Research, 2008
- Induction of Mxi1-SRα by FOXO3a Contributes to Repression of Myc-Dependent Gene ExpressionMolecular and Cellular Biology, 2007
- FKHRL1-mediated expression of Noxa and Bim induces apoptosis via the mitochondria in neuroblastoma cellsCell Death & Differentiation, 2006