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Original Article | Open Access

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

Haihua Tian1,2, Jinchang Pan1,2, Shuai Fang1,2, Chengwei Zhou1,3, Hui Tian4, Jinxian He4, Weiyu Shen4, Xiaodan Meng1,2, Xiaofeng Jin1,2, Zhaohui Gong1,2 ( )
Department of Biochemistry and Molecular Biology, Ningbo University School of Medicine, Ningbo 315211, China
Zhejiang Province Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China
Department of Thoracic Surgery, The Affiliated Hospital of Ningbo University School of Medicine, Ningbo 315020, China
Department of Thoracic Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo 315048, China
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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

lung cancerAntisense long noncoding RNADPP10-AS1hypomethylationmalignant process

Electronic Supplementary Material

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Cancer Biology & Medicine
Volume 18 Issue 3,
August 2021
Pages 675-692
DOI: 10.20892/j.issn.2095-3941.2020.0136
Cite this article:
Tian H, Pan J, Fang S, et al. LncRNA DPP10-AS1 promotes malignant processes through epigenetically activating its cognate gene DPP10 and predicts poor prognosis in lung cancer patients. Cancer Biology & Medicine, 2021, 18(3): 675-692. https://doi.org/10.20892/j.issn.2095-3941.2020.0136

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Received: 25 March 2020
Accepted: 21 August 2020
Published: 01 August 2021
©2021 Cancer Biology & Medicine.

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