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Long non-coding RNA DLGAP1-AS1 modulates the development of non-small-cell lung cancer via the microRNA-193a-5p/DTL axis.
- Source :
-
Laboratory investigation; a journal of technical methods and pathology [Lab Invest] 2022 Nov; Vol. 102 (11), pp. 1182-1191. Date of Electronic Publication: 2022 Oct 01. - Publication Year :
- 2022
-
Abstract
- 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.<br /> (© 2022. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.)
- Subjects :
- Mice
Animals
Humans
Mice, Nude
Gene Expression Regulation, Neoplastic
Cell Proliferation genetics
Cell Movement genetics
Cell Line, Tumor
RNA-Binding Proteins metabolism
Nuclear Proteins genetics
RNA, Long Noncoding genetics
RNA, Long Noncoding metabolism
Carcinoma, Non-Small-Cell Lung pathology
Lung Neoplasms metabolism
MicroRNAs genetics
MicroRNAs metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1530-0307
- Volume :
- 102
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Laboratory investigation; a journal of technical methods and pathology
- Publication Type :
- Academic Journal
- Accession number :
- 36183046
- Full Text :
- https://doi.org/10.1038/s41374-022-00831-6