Non-small cell lung cancer (NSCLC) is one of the most malignant cancers worldwide. A growing number of studies have suggested that long noncoding RNAs (lncRNAs) play a key role in the progression of non-small cell lung cancer (NSCLC). Here, we report a novel lncRNA DLGAP1 antisense RNA 1 (DLGAP1-AS1) that exhibits oncogenic properties in NSCLC. The lncRNA DLGAP1-AS1 and denticleless protein homolog (DTL) presented upregulated expression, but microRNA-193a-5p (miR-193a-5p) showed downregulated expression in cancerous tissues of human lung samples from 48 patients with NSCLC. Partial loss of lncRNA DLGAP1-AS1 reduced malignant cell viability, migration, and invasion but induced apoptosis. Dual-luciferase reporter gene, RNA pull-down and RNA binding protein immunoprecipitation assays demonstrated enrichment of lncRNA DLGAP1-AS1 in miR-193a-5p and Argonaute 2, suggesting that lncRNA DLGAP1-AS1 modulated DTL, a putative target of miR-193a-5p. We also found that restoration of miR-193a-5p rescued NSCLC cell biological functions affected by overexpression of lncRNA DLGAP1-AS1. Silencing lncRNA DLGAP1-AS1 was found to reduce the tumorigenesis of NSCLC cells xenografted into nude mice, which was rescued by DTL overexpression. In conclusion, our study highlights a novel regulatory network of the lncRNA DLGAP1-AS1/miR-193a-5p/DTL axis in NSCLC, providing a potential therapeutic strategy for NSCLC.
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This work is supported by National Natural Science Foundation of China (No. 31101641) and the project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
The authors declare no competing interests.
Ethics approval and consent to participate
The study was performed with the approval of the Ethics Committee of The First Affiliated Hospital of Soochow University. Each patient provided informed written consent prior to study recruitment. All experiments in the present study were conducted in strict accordance with the Helsinki Declaration. The animal experiment strictly adhered to the principle to minimize the pain, suffering, and discomfort to experimental animals. The protocol was approved by the Animal Ethics Committee of The First Affiliated Hospital of Soochow University.
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Pan, X., Chen, S., Ye, L. et al. Long non-coding RNA DLGAP1-AS1 modulates the development of non-small-cell lung cancer via the microRNA-193a-5p/DTL axis. Lab Invest 102, 1182–1191 (2022). https://doi.org/10.1038/s41374-022-00831-6