Long non-coding RNA TDRG1 aggravates lung cancer stemness by binding to Sox2 mRNA
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Updated: Aug 19, 2025
RNA Pull-down Procedure to Identify RNA Targets of a Long Non-coding RNA
Published on: April 10, 2018
You Lu1, Jing Cheng2, Qixing Mao2
1Department of Interventional Radiology, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, China.
Abstract:
The roles of long non-coding RNA TDRG1 have been revealed in several tumors, especially its roles in CSC progression have been recently elucidated; However, its effects in lung CSC progression have not been revealed. In the present study, we collected 3D non-adherent spheres as the CSC model to measure lncRNA TDRG1 level in lung CSC and the parental lung cancer cells, and found that TDRG1 level was significantly upregulated in lung CSCs compared to that of parental lung cancer cells. Then we constructed the lung CSCs with or without TDRG1 stable knockdown and lung cancer cells with or without TDRG1 stable overexpression. It was found that TDRG1 positively regulated lung cancer stemness. Mechanistically, we identified that TDRG1 directly bound to Sox2 mRNA, which is a critical stemness regulator, enhanced its mRNA stability, and thus increased Sox2 expression. Indeed, we demonstrated that TDRG1 aggravated lung cancer stemness dependent on Sox2 expression. Thus, this study suggests that TDRG1 is a critical stemness promoter of lung cancer cells by acting as a stabilizer for Sox2 mRNA.
Insights
Long non-coding RNA TDRG1 promotes lung cancer stemness by stabilizing Sox2 mRNA. This study reveals TDRG1 as a key regulator in lung cancer stem cell progression, offering potential therapeutic targets.
Area of Science:
- Molecular Biology
- Oncology
- RNA Biology
Background:
- Long non-coding RNA TDRG1's role in various cancers is known, but its function in lung cancer stem cells (CSCs) remains unclear.
- Cancer stem cells drive tumor progression and therapeutic resistance.
- Understanding regulators of lung CSCs is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of lncRNA TDRG1 in lung CSC progression.
- To elucidate the molecular mechanism by which TDRG1 affects lung CSCs.
- To determine if TDRG1 is a potential therapeutic target in lung cancer.
Main Methods:
- Established a 3D non-adherent sphere model for lung CSCs.
- Measured lncRNA TDRG1 levels in lung CSCs and parental lung cancer cells.
- Generated stable knockdown/overexpression cell lines for TDRG1.
- Investigated the interaction between TDRG1 and Sox2 mRNA.
- Assessed the impact of TDRG1 on lung cancer stemness.
Main Results:
- TDRG1 was significantly upregulated in lung CSCs compared to parental cells.
- TDRG1 overexpression enhanced lung cancer stemness, while knockdown reduced it.
- TDRG1 directly binds to Sox2 mRNA, increasing its stability and expression.
- TDRG1 promotes lung cancer stemness in a Sox2-dependent manner.
Conclusions:
- TDRG1 acts as a critical promoter of lung cancer stemness.
- TDRG1 stabilizes Sox2 mRNA, thereby enhancing stemness.
- TDRG1 is a potential therapeutic target for lung cancer treatment.
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