LncRNA DPP10-AS1 promotes malignant processes through epigenetically activating its cognate gene DPP10 and predicts poor prognosis in lung cancer patients

Cancer Biol Med. 2021 Jun 9;j.issn.2095-3941.2020.0136. doi: 10.20892/j.issn.2095-3941.2020.0136. Online ahead of print.

Abstract

Objective: The purpose of this study was to explore the function and gene expression regulation of the newly identified lncRNA DPP10-AS1 in lung cancer, and its potential value as a prognostic biomarker.

Methods: qRT-PCR and Western blot were conducted to detect the expression of DDP10-AS1 and DPP10 in lung cancer cell lines and tissues. The effects of DDP10-AS1 on DPP10 expression, cell growth, invasion, apoptosis, and in vivo tumor growth were investigated in lung cancer cells by Western blot, rescue experiments, colony formation, flow cytometry, and xenograft animal experiments.

Results: The novel antisense lncRNA DPP10-AS1 was found to be highly expressed in cancer tissues (P < 0.0001), and its upregulation predicted poor prognosis in patients with lung cancer (P = 0.0025). Notably, DPP10-AS1 promoted lung cancer cell growth, colony formation, and cell cycle progression, and repressed apoptosis in lung cancer cells by upregulating DPP10 expression. Additionally, DPP10-AS1 facilitated lung tumor growth via upregulation of DPP10 protein in a xenograft mouse model. Importantly, DPP10-AS1 positively regulated DPP10 gene expression, and both were coordinately upregulated in lung cancer tissues. Mechanically, DPP10-AS1 was found to associate with DPP10 mRNA but did not enhance DPP10 mRNA stability. Hypomethylation of DPP10-AS1 and DPP10 contributed to their coordinate upregulation in lung cancer.

Conclusions: These findings indicated that the upregulation of the antisense lncRNA DPP10-AS1 promotes lung cancer malignant processes and facilitates tumorigenesis by epigenetically regulating its cognate sense gene DPP10. DPP10-AS1 may serve as a candidate prognostic biomarker and a potential therapeutic target in lung cancer.

Keywords: Antisense long noncoding RNA; DPP10-AS1; hypomethylation; lung cancer; malignant process.