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Posttranscriptional deregulation of Src due to aberrant miR34a and miR203 contributes to gastric cancer development
Qiang Hao1, Xiaozhao Lu, Nannan Liu
1The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, The Fourth Military Medical University, Xi'an 710032, China.
Abstract:
Gastric cancer remains the main cause of cancer death all around the world, and upregulated activation of the nonreceptor tyrosine kinase c-SRC (SRC) is a key player in the development. In this study, we found that expression of Src is also increased in clinical gastric cancer samples, with the protein level increased more significantly than that at the RNA level. Further study revealed that miR34a and miR203, two tumor suppressive miRNAs, inversely correlate with the expression of Src. Restoration of miR34a and miR203 decreased Src expression in gastric cancer cell lines, which in turn inhibited cell growth and cell migration. In summary, our study here revealed that posttranscriptional regulation of Src contributes to the deregulated cell growth and metastasis in gastric cancer, and targeting Src by miR34a or miR203 mimics would be a promising strategy in therapy.
Insights
Gastric cancer involves increased c-SRC (SRC) protein. Tumor suppressive microRNAs miR34a and miR203 target SRC, inhibiting cancer cell growth and migration, offering a potential new therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Gastric cancer is a leading cause of cancer mortality worldwide.
- Upregulated nonreceptor tyrosine kinase c-SRC (SRC) is implicated in gastric cancer development.
- SRC protein levels are elevated in clinical gastric cancer samples, more so than RNA levels.
Purpose of the Study:
- To investigate the role of posttranscriptional regulation in SRC expression in gastric cancer.
- To explore the relationship between tumor suppressive microRNAs (miRNAs) and SRC expression.
- To evaluate the therapeutic potential of targeting SRC via miRNAs in gastric cancer.
Main Methods:
- Analysis of SRC expression in clinical gastric cancer samples.
- Correlation studies between SRC expression and tumor suppressive miRNAs (miR34a, miR203).
- Restoration of miR34a and miR203 in gastric cancer cell lines to assess effects on SRC expression, cell growth, and migration.
Main Results:
- SRC expression, particularly at the protein level, is significantly increased in gastric cancer.
- Expression of tumor suppressive miRNAs miR34a and miR203 inversely correlates with SRC expression.
- Restoring miR34a and miR203 reduced SRC levels, inhibiting gastric cancer cell growth and migration.
Conclusions:
- Posttranscriptional regulation of SRC by miR34a and miR203 plays a crucial role in gastric cancer progression.
- Targeting SRC using miR34a or miR203 mimics presents a promising therapeutic strategy for gastric cancer.
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