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Published on: March 30, 2019
LncRNA PGM5-AS1 inhibits non-small cell lung cancer progression by targeting miRNA-423-5p/SLIT2 axis
Jiajun Wang1, Jun Ye1, Yuxue Dang2
1Department of Thoracic Surgery, The First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang, 110001, Liaoning, China.
Abstract:
Non-small cell lung cancer (NSCLC) is a common and aggressive primary malignancy worldwide. Dysregulation of long non-coding RNAs (lncRNAs) has been shown to play an essential regulatory role in multiple cancers. However, the role of PGM5-AS1 in NSCLC remains unclear. Here, we found that PGM5-AS1 was down-regulated in NSCLC tissues and cells. Furthermore, reduced PGM5-AS1 expression levels were associated with larger tumor size, positive lymph node metastasis, advanced TNM stage and worse prognosis. We found that overexpression of PGM5-AS1 inhibited cell proliferation and metastasis, and induced apoptosis and G0/G1 cell cycle arrest in NSCLC cell lines. Using dual luciferase gene reporter and RNA immunoprecipitation assays, we confirmed that miR-423-5p interacted with PGM5-AS1, and that their expression levels were negatively correlated in NSCLC tissues. miR-423-5p was also found to reverse PGM5-AS1-induced malignant biological behavior. Moreover, we identified slit guidance ligand 2 (SLIT2) as a target gene of miR-423-5p. Using a dual luciferase gene reporter assay, we confirmed the regulatory relationship between SLIT2 and miR-423-5p and demonstrated that their expression levels were negatively correlated. Our rescue experiments showed that SLIT2 knockdown reversed miR-423-5p-mediated effects. Overall, this study identifies PGM5-AS1 as a potential prognostic biomarker for NSCLC and shows that PGM5-AS1 suppresses NSCLC development by regulating the miR-423-5p/SLIT2 axis.
Insights
Long non-coding RNA PGM5-AS1 is downregulated in non-small cell lung cancer (NSCLC), suppressing tumor growth and metastasis by regulating the miR-423-5p/SLIT2 pathway, suggesting its potential as a prognostic biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) is a prevalent and aggressive malignancy.
- Long non-coding RNAs (lncRNAs) are implicated in cancer development, but the role of PGM5-AS1 in NSCLC is not well understood.
Purpose of the Study:
- To investigate the role and mechanism of PGM5-AS1 in NSCLC.
- To determine if PGM5-AS1 can serve as a prognostic biomarker for NSCLC.
Main Methods:
- Analysis of PGM5-AS1 expression in NSCLC tissues and cell lines.
- Overexpression and knockdown experiments to assess PGM5-AS1's functional impact on NSCLC cells.
- Dual luciferase reporter and RNA immunoprecipitation assays to confirm interactions between PGM5-AS1, miR-423-5p, and SLIT2.
- Rescue experiments to validate the regulatory axis.
Main Results:
- PGM5-AS1 was significantly downregulated in NSCLC tissues and correlated with advanced stage and poor prognosis.
- Overexpression of PGM5-AS1 inhibited NSCLC cell proliferation, metastasis, and induced apoptosis and cell cycle arrest.
- PGM5-AS1 directly targeted miR-423-5p, which in turn targeted SLIT2, forming the PGM5-AS1/miR-423-5p/SLIT2 axis.
- Restoration of SLIT2 expression reversed the effects of miR-423-5p.
Conclusions:
- PGM5-AS1 acts as a tumor suppressor in NSCLC by inhibiting the miR-423-5p/SLIT2 pathway.
- PGM5-AS1 is a potential prognostic biomarker for NSCLC.
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