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Published on: April 6, 2012
Long Noncoding RNA GAS5 Suppresses Tumorigenesis by Inhibiting miR-23a Expression in Non-Small Cell Lung Cancer
Abstract:
Previous studies reported that elevated expression of long noncoding RNA (lncRNA) GAS5 led to the arrest of non-small cell lung cancer (NSCLC) cell growth and a promotion of apoptosis both in vitro and in vivo. However, its underlying molecular mechanism in NSCLC is still unclear. In the present study, we noted that GAS5 was downregulated in NSCLC tissues and cells and was negatively correlated with miR-23a expression. Luciferase reporter assay and qRT-PCR analysis demonstrated that GAS5 directly interacted with miR-23a and reversely regulated its expression. miR-23a overexpression markedly promoted NSCLC cell proliferation and invasion, while GAS5 overexpression dramatically inhibited NSCLC cell proliferation and invasion and promoted apoptosis. Functional analysis indicated that miR-23a overexpression significantly abolished GAS5 overexpression-induced inhibition of proliferation and invasion, as well as promotion of apoptosis in NSCLC cells. Moreover, xenograft experiments further revealed that upregulation of GAS5 notably impaired the growth of transplanted tumors by suppressing miR-23a in nude mice. These results suggested that overexpression of lncRNA GAS5 inhibits tumorigenesis of NSCLC by inhibiting miR-23a in vitro and in vivo, providing a potential therapeutic strategy for patients with NSCLC.
Insights
Overexpression of the long noncoding RNA GAS5 inhibits non-small cell lung cancer (NSCLC) growth by suppressing miR-23a. This finding offers a potential new therapeutic strategy for NSCLC patients.
Area of Science:
- Molecular Biology
- Oncology
- RNA Biology
Background:
- Previous studies suggested long noncoding RNA GAS5 (lncRNA GAS5) inhibits non-small cell lung cancer (NSCLC) progression.
- The precise molecular mechanisms underlying lncRNA GAS5's role in NSCLC remain incompletely understood.
Purpose of the Study:
- To investigate the molecular mechanism of lncRNA GAS5 in NSCLC.
- To explore the relationship between lncRNA GAS5 and miR-23a in NSCLC.
- To evaluate the therapeutic potential of lncRNA GAS5 in NSCLC.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and luciferase reporter assays were used to analyze the interaction between GAS5 and miR-23a.
- In vitro cell proliferation, invasion, and apoptosis assays were performed.
- In vivo xenograft experiments in nude mice were conducted to assess tumor growth inhibition.
Main Results:
- GAS5 was found to be downregulated in NSCLC tissues and negatively correlated with miR-23a expression.
- GAS5 directly interacted with and inhibited miR-23a expression.
- Overexpression of GAS5 inhibited NSCLC cell proliferation and invasion while promoting apoptosis, effects abolished by miR-23a.
- Upregulation of GAS5 suppressed tumor growth in vivo by inhibiting miR-23a.
Conclusions:
- lncRNA GAS5 suppresses NSCLC tumorigenesis by inhibiting miR-23a.
- GAS5 represents a potential therapeutic target for NSCLC treatment.
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