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Updated: Dec 14, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Investigation of Targeting Relationship between Micro-Rna-22 and Vegfr3 in Lung Squamous Cell Carcinoma
Zheng Dong1, Qing-Hua Xu1, Yuan-Bin Zhu1
1Department of Respiration, Linyi Central Hospital, Linyi, China.
Aim:
The present study explored the clinical significance of microRNA-22 (miR-22) expression in lung squamous cell carcinoma and to explore the targeting relationship with vascular endothelial growth factor receptor 3 (VEGFR3).
Methods:
A total of 49 patients with lung squamous cell carcinoma who underwent surgical treatment were selected. The expression of miR-22 was detected by fluorescence quantitative realtime PCR (qPCR), the expression of VEGFR3 was detected by Western blotting assays, and D240 labeled microlymphatic vessels density (MLVD) was detected by immunohistochemistry (IHC). Lung squamous cell carcinoma cell line SK-MES-1 was selected and the targeting relationship between miR-22 and VEGFR3 was analyzed by double luciferase reporter gene assay. Western blotting assays were used to detect the expression of vascular endothelial growth factor-D (VEGFD) and D240 in the blank control group, empty vector transfection group, miR-22 transfection group, miR-22 and VEGFR3 co-transfection group.
Results:
The expression range of miR-22 in lung squamous cell carcinoma was 0.8-3.5. The expression of miR-22 in lung squamous cell carcinoma was significantly different by tumor maximum diameter, lymph node metastasis, vascular invasion and TNM stage. The expression of miR-22 was linked to survival time. There was a negative correlation between miR-22 and VEGFR3, miR-22 and MLVD. Double luciferase reporter gene assays showed that miR-22 reduced the luciferase activity of pGL3-VEGFR3-WT transfected cells. Compared with the control group, the expression of VEGF-D and D2-40 in the miR-22 transfection group was significantly decreased. However, VEGF-D and D240 in the miR-22 and VEGFR3 co-transfection group reversed the changes.
Conclusion:
We assumed that the abnormal expression of miR-22 in lung squamous cell carcinoma may be involved in the development and progression of lung squamous cell carcinoma. MiR-22 negatively regulated the target gene VEGFR3 to mediate lymphangiogenesis. The expression of miR-22 may also be linked to the prognosis of the disease.
Insights
MicroRNA-22 (miR-22) expression is clinically significant in lung squamous cell carcinoma, negatively regulating vascular endothelial growth factor receptor 3 (VEGFR3) to impact lymphangiogenesis and patient prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung squamous cell carcinoma (LSCC) is a major subtype of non-small cell lung cancer.
- Understanding the molecular mechanisms driving LSCC progression is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the clinical significance of microRNA-22 (miR-22) expression in LSCC.
- To elucidate the targeting relationship between miR-22 and vascular endothelial growth factor receptor 3 (VEGFR3).
Main Methods:
- Analysis of miR-22 expression in 49 LSCC patients using qPCR.
- Detection of VEGFR3 and microlymphatic vessels density (MLVD) via Western blotting and immunohistochemistry.
- Luciferase reporter assays to confirm miR-22 targeting of VEGFR3.
- In vitro experiments assessing VEGF-D and D240 expression after miR-22 and VEGFR3 co-transfection.
Main Results:
- miR-22 expression levels in LSCC correlated with tumor size, lymph node metastasis, vascular invasion, and TNM stage.
- A negative correlation was observed between miR-22 and VEGFR3 expression, and between miR-22 and MLVD.
- miR-22 directly targeted VEGFR3, reducing its activity and subsequently decreasing VEGF-D and D240 expression.
- Co-transfection of miR-22 and VEGFR3 reversed these effects.
Conclusions:
- Abnormal miR-22 expression is implicated in LSCC development and progression.
- miR-22 negatively regulates VEGFR3, playing a role in lymphangiogenesis.
- miR-22 expression may serve as a prognostic biomarker for LSCC.
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