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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
miR-125a regulates angiogenesis of gastric cancer by targeting vascular endothelial growth factor A
Jun Dai1, Jinyu Wang2, Lili Yang1
1Institute of Pathology of Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
Abstract:
A recent discovery revealed that microRNAs (miRNAs) have an essential effect in the development and progression of gastric cancer (GC). It has already been shown that miR‑125a may inhibit tumor development by targeting human epidermal growth factor receptor-2 (Her-2) in GC; however, the other roles of miR‑125a in gastric cancer remained to be explored. Our study confirmed that miR‑125a was indeed capable of modulating the expression of VEGF-A in gastric cancer cells. In vitro, low expression of miR‑125a was able to maintain the secretion of VEGF-A, while the latter increased Akt phosphorylation level in endothelial cells and thereby promoted the proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs). Our investigation showed that miR‑125a expression decreased significantly in gastric cancer comparing with normal gastric tissue and was negatively correlated with the expression of VEGF-A (P<0.05). In vivo, the expression of miR‑125a was inversely proportional to microvessel density (MVD) (r=-0.5382, P<0.001). The results of this study suggested that low expression of miR‑125a predict a worse survival in gastric cancer patients. Collectively, our results indicated that miR‑125a regulated the paracrine of VEGF-A in gastric cancer and thereby controlled the angiogenesis of the tumor.
Insights
MicroRNA-125a (miR-125a) suppresses gastric cancer growth by inhibiting VEGF-A, a key factor in tumor angiogenesis. Low miR-125a levels correlate with poor patient survival, highlighting its therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNAs (miRNAs) play a critical role in gastric cancer (GC) development and progression.
- While miR-125a's tumor-inhibitory effects via targeting Her-2 in GC are known, its other functions remain under investigation.
Purpose of the Study:
- To investigate the role of miR-125a in regulating angiogenesis in gastric cancer.
- To explore the relationship between miR-125a expression and vascular endothelial growth factor A (VEGF-A) in GC.
Main Methods:
- In vitro studies using gastric cancer cells and human umbilical vein endothelial cells (HUVECs) to assess miR-125a's effect on VEGF-A secretion and endothelial cell function.
- Analysis of miR-125a and VEGF-A expression levels in gastric cancer tissues compared to normal tissues.
- In vivo assessment of the correlation between miR-125a expression and microvessel density (MVD) in tumors.
Main Results:
- miR-125a modulates VEGF-A expression in gastric cancer cells.
- Low miR-125a expression leads to increased VEGF-A secretion, promoting HUVEC proliferation, migration, and angiogenesis.
- miR-125a expression is significantly decreased in gastric cancer tissues and negatively correlated with VEGF-A expression.
- In vivo, miR-125a expression is inversely proportional to microvessel density (MVD).
Conclusions:
- miR-125a regulates the paracrine secretion of VEGF-A in gastric cancer.
- This regulation impacts tumor angiogenesis, with low miR-125a expression predicting worse survival in gastric cancer patients.
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