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Published on: March 30, 2019
LncRNA SBF2-AS1 affects the radiosensitivity of non-small cell lung cancer via modulating microRNA-302a/MBNL3 axis
Zhanwu Yu1, Gebang Wang1, Chenlei Zhang1
1Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, P.R. China.
Abstract:
Background: Long non-coding RNAs (lncRNAs) have been reported to participate in many diseases including non-small cell lung cancer (NSCLC), thus our objective was to investigate the impact of lncRNA SBF2-AS1 modulating microRNA-302a (miR-302a) expression on radiosensitivity of NSCLC.Methods: The expression of SBF2-AS1, miR-302a and muscleblind-like 3 (MBNL3) in NSCLC tissues of the radiotherapy-sensitive and radiotherapy-resistant groups was tested. The radiosensitivity of parent and resistant strains (NCI-H1299 and NCI-H1299R cells) was detected. Further, cells were treated with si-SBF2-AS1 and miR-302a mimics to determine their roles in proliferation and apoptosis of parent strain and resistant strain cells as well as transfected cells. The in-vivo growth capacity of the cells and the effect of radiotherapy on tumor size of NSCLC were detected.Results: Up-regulated SBF2-AS1 and MBNL3 and down-regulated miR-302a in NSCLC tissues of the radiotherapy resistant group. Overexpression of SBF2-AS1 and MBNL3 and low expression of miR-302a were witnessed in NCI-H1299R cells. Down-regulated SBF2-AS1 or up-regulated miR-302a suppressed the proliferation while boosted the apoptosis of NCI-H1299 cells and decreased the radioresistance of the NCI-H1299R cells. Silencing SBF2-AS1 or up-regulating miR-302a restrained tumor growth in vivo.Conclusion: Our study presents that high expression of miR-302a or inhibition of SBF2-AS1 can enhance the radiosensitivity and apoptosis of NSCLC cells through downregulation of MBNL3, which is a therapeutic target for NSCLC.
Insights
Inhibiting lncRNA SBF2-AS1 or increasing microRNA-302a enhances non-small cell lung cancer radiosensitivity. This modulation targets MBNL3, offering a potential therapeutic strategy for NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are implicated in non-small cell lung cancer (NSCLC) pathogenesis.
- Understanding lncRNA roles is crucial for developing novel NSCLC therapies.
Purpose of the Study:
- To investigate the effect of lncRNA SBF2-AS1 on microRNA-302a (miR-302a) expression.
- To determine the impact of this interaction on NSCLC radiosensitivity.
Main Methods:
- Assessed SBF2-AS1, miR-302a, and MBNL3 expression in NSCLC tissues and cell lines.
- Utilized cell transfection with si-SBF2-AS1 and miR-302a mimics.
- Evaluated proliferation, apoptosis, and radiosensitivity in vitro and tumor growth in vivo.
Main Results:
- Radiotherapy-resistant NSCLC tissues and cells showed elevated SBF2-AS1 and MBNL3, with decreased miR-302a.
- Downregulating SBF2-AS1 or upregulating miR-302a reduced proliferation and increased apoptosis in NSCLC cells.
- Inhibition of SBF2-AS1 or enhancement of miR-302a decreased radioresistance and suppressed tumor growth in vivo.
Conclusions:
- High miR-302a expression or SBF2-AS1 inhibition enhances NSCLC radiosensitivity and apoptosis.
- This effect is mediated through the downregulation of MBNL3.
- MBNL3 represents a potential therapeutic target for improving NSCLC radiosensitivity.
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