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Long Noncoding RNA GAS5 Acts As A Tumor Suppressor In Laryngeal Squamous Cell Carcinoma Via miR-21
Kexing Lyu1, Yang Xu1, Huijun Yue1
1Department of Otolaryngology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China.
Purpose:
Long noncoding RNAs (lncRNAs) have been identified as an important class of noncoding RNAs that are deeply involved in multiple biological processes in tumorigenesis. This study is to investigate the critical roles and biological function of lncRNA growth arrest-specific 5 (GAS5) in tumorigenesis of laryngeal squamous cell carcinoma (LSCC).
Patients And Methods:
A total of 59 samples of LSCC and paired adjacent tissue, as well as corresponding clinicopathological information were collected. GAS5 expression in both LSCC tissues and human SUN1076 and SNU899 cell lines were analyzed by Real-time quantitative RT-PCR method. Ectopic expression of GAS5 by vector transfection in LSCC cell lines and followed by in vitro experiments was to investigate the critical roles and function of GAS5 in LSCC. Cell Counting Kit 8 (CCK8) assay and PE/7AAD Annexin V Apoptosis analysis was to evaluate cell proliferation ability and cell apoptosis. Co-transfection of GAS5 and miR-21 was to explore the interaction between GAS5 and miR-21 in LSCC. BAX and CDK6 protein level were analyzed by western blot method.
Results:
This study demonstrated that GAS5 was significantly downregulated in LSCC tissue and human LSCC cell lines. GAS5 levels were correlated with the clinicopathological features of LSCC patients. In addition, the ectopic expression of GAS5 significantly inhibited cell proliferation and promoted apoptosis. Co-expression analyses indicated that GAS5 is negatively correlated with miR-21 in LSCC tissues. Overexpression of miR-21 eliminated GAS5-mediated cell apoptosis and proliferation suppression. Furthermore, GAS5, which upregulated BAX mRNA expression and downregulated CDK6 mRNA expression, was reversed by ectopic expression of miR-21.
Conclusion:
GAS5 suppresses LSCC progression through the negative regulation of miR-21 and its targets involved in cell proliferation and apoptosis, indicating that GAS5 may serve as a biomarker and potential target for LSCC therapy.
Insights
Long noncoding RNA GAS5 is downregulated in laryngeal squamous cell carcinoma (LSCC). Restoring GAS5 inhibits LSCC progression by targeting miR-21, suggesting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis.
- Laryngeal squamous cell carcinoma (LSCC) is a significant health concern.
- Understanding the function of specific lncRNAs in LSCC is vital for developing new therapies.
Purpose of the Study:
- To investigate the role and biological function of lncRNA growth arrest-specific 5 (GAS5) in LSCC tumorigenesis.
- To determine the expression levels of GAS5 in LSCC tissues and cell lines.
- To explore the interaction between GAS5 and miR-21 in LSCC.
Main Methods:
- Analysis of GAS5 expression in 59 LSCC tissues and adjacent samples using Real-time quantitative RT-PCR.
- In vitro experiments involving ectopic expression of GAS5 in LSCC cell lines.
- Cell proliferation (CCK8 assay) and apoptosis (Annexin V analysis) assays were performed.
- Co-transfection of GAS5 and miR-21 to study their interaction and effects on BAX and CDK6 protein levels via Western blot.
Main Results:
- GAS5 was significantly downregulated in LSCC tissues and cell lines.
- Ectopic expression of GAS5 inhibited LSCC cell proliferation and promoted apoptosis.
- GAS5 negatively correlated with miR-21 expression in LSCC.
- Overexpression of miR-21 reversed the effects of GAS5 on cell apoptosis and proliferation, and modulated BAX and CDK6 expression.
Conclusions:
- GAS5 suppresses LSCC progression by negatively regulating miR-21 and its downstream targets.
- GAS5 functions as a tumor suppressor in LSCC.
- GAS5 holds potential as a biomarker and therapeutic target for LSCC.
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