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Down-Regulation of miR-7 in Gastric Cancer Is Associated With Elevated LDH-A Expression and Chemoresistance to
Hui-Fang Jin1, Ju-Feng Wang2, Ming Shao1
1Department of Bloood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Abstract:
MicroRNAs (miRNAs) are dysregulated in the context of many cancer types, making them potentially ideal diagnostic or therapeutic targets in patients in which they are aberrantly expressed. In the present study, we found miR-7 to be downregulated in gastric cancer (GC), and we further determined its expression to be closely linked to GC sensitivity to the chemotherapeutic compound cisplatin. This effect appears to be at least partially attributable to the regulation of LDH-A, which is a miR-7 target gene and expression of LDH-A is negatively correlated with miR-7 expression in primary GC tumor samples. When upregulated, we also determined that miR-7 was able to inhibit the proliferation, colony formation, and glycolysis of GC cells owing to its regulation of LDH-A. Moreover, overexpression of miR-7 render cells more sensitive to cisplatin. Our results thus provide novel evidence that miR-7 is a key mediator of GC growth and chemosensitivity through its regulation of LDH-A, thus potentially highlighting this pathway as a therapeutic target for treating affected patients.
Insights
MicroRNAs (miRNAs) like miR-7 are crucial in gastric cancer (GC). Downregulated miR-7 in GC cells increases proliferation and reduces cisplatin sensitivity by affecting LDH-A, suggesting a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression.
- Dysregulated miRNA expression is common in various cancers, including gastric cancer (GC).
- miRNAs represent potential diagnostic and therapeutic targets in oncology.
Purpose of the Study:
- To investigate the role of miR-7 in gastric cancer (GC).
- To determine the relationship between miR-7 expression and GC sensitivity to cisplatin.
- To elucidate the molecular mechanisms underlying miR-7's function in GC.
Main Methods:
- Quantitative real-time PCR to measure miR-7 expression in GC samples.
- Analysis of the correlation between miR-7 expression and clinicopathological features.
- Western blotting and luciferase reporter assays to validate LDH-A as a miR-7 target.
- Cell proliferation, colony formation, and glycolysis assays in GC cells with altered miR-7 levels.
- Assessment of GC cell sensitivity to cisplatin following miR-7 modulation.
Main Results:
- miR-7 was found to be significantly downregulated in gastric cancer tissues.
- Lower miR-7 expression correlated with reduced sensitivity to cisplatin chemotherapy.
- LDH-A was identified as a direct target of miR-7, with inverse expression correlation in GC tumors.
- Overexpression of miR-7 inhibited GC cell proliferation, colony formation, and glycolysis.
- miR-7 upregulation enhanced the sensitivity of GC cells to cisplatin.
Conclusions:
- miR-7 acts as a tumor suppressor in gastric cancer.
- miR-7 regulates GC cell growth and glycolysis via targeting LDH-A.
- miR-7 plays a critical role in modulating GC chemosensitivity to cisplatin.
- The miR-7/LDH-A pathway presents a potential therapeutic strategy for gastric cancer treatment.
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