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Published on: May 4, 2016
FOXO3a-dependent Parkin regulates the development of gastric cancer by targeting ATP-binding cassette transporter E1
Dan Ding1,2, Xiang Ao1,2, Mengyang Li1
1School of Basic Medical Sciences, College of Medicine, Qingdao University, Qingdao, China.
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.
Insights
This study reveals a new pathway involving FOXO3a, Parkin, and ABCE1 in gastric cancer (GC). This FOXO3a-Parkin-ABCE1 axis impacts GC cell growth, movement, and cell death, offering a potential new therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Gastric cancer (GC) is a leading cause of cancer death in China.
- Parkin functions as a tumor suppressor, but its mechanism in GC is not fully understood.
- Forkhead box O3a (FOXO3a) is a key regulator of cancer cell behavior.
Purpose of the Study:
- To elucidate the mechanism of Parkin in gastric cancer.
- To identify the regulatory pathway involving FOXO3a, Parkin, and ABCE1 in GC.
- To explore potential therapeutic targets for GC.
Main Methods:
- Observing Parkin expression in GC cells and patient tissues.
- Investigating the effects of doxorubicin (DOX) on Parkin expression and GC cells.
- Analyzing the regulatory relationship between FOXO3a, Parkin, and ABCE1 at the transcriptional level.
Main Results:
- Parkin expression was low in GC cells and tissues; Parkin inhibited GC cell proliferation and migration.
- Doxorubicin (DOX) increased Parkin expression and enhanced its anti-cancer effects.
- FOXO3a suppressed GC cell proliferation and migration while promoting apoptosis by regulating Parkin transcription.
- Parkin inhibited proliferation and migration and promoted apoptosis by downregulating ABCE1 expression.
Conclusions:
- A novel regulatory axis, FOXO3a-Parkin-ABCE1, was identified in gastric cancer.
- This axis significantly modulates GC cell proliferation, migration, and apoptosis.
- The FOXO3a-Parkin-ABCE1 pathway represents a potential therapeutic target for gastric cancer treatment.
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