Identification of a novel intermittent hypoxia-related prognostic lncRNA signature and the ceRNA of lncRNA GSEC/miR-873-3p/EGLN3 regulatory axis in lung adenocarcinoma

Peijun Liu; Long Zhou; Hao Chen; Yang He; Guangcai Li; Ke Hu

doi:10.7717/peerj.16242

Identification of a novel intermittent hypoxia-related prognostic lncRNA signature and the ceRNA of lncRNA GSEC/miR-873-3p/EGLN3 regulatory axis in lung adenocarcinoma

PeerJ. 2023 Oct 10:11:e16242. doi: 10.7717/peerj.16242. eCollection 2023.

Authors

Peijun Liu^#¹, Long Zhou^#², Hao Chen¹, Yang He¹, Guangcai Li², Ke Hu¹

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
² Department of Respiratory and Critical Care Medicine, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, China.

^# Contributed equally.

Abstract

Background: Lung adenocarcinoma (LUAD) is still the most prevalent type of respiratory cancer. Intermittent hypoxia can increase the mortality and morbidity associated with lung cancer. Long non-coding RNAs (lncRNAs) are crucial in lung adenocarcinoma. However, the effects of intermittent hypoxia-related long non-coding RNAs (IHRLs) on lung adenocarcinoma are still unknown.

Method: In the current research, eight IHRLs were selected to create a prognostic model. The risk score of the prognostic model was evaluated using multivariate and univariate analyses, and its accuracy and reliability were validated using a nomogram and ROC. Additionally, we investigated the relationships between IHRLs and the immune microenvironment.

Result: Our analysis identified GSEC, AC099850.3, and AL391001.1 as risk lncRNAs, while AC010615.2, AC010654.1, AL513550.1, LINC00996, and LINC01150 were categorized as protective lncRNAs. We observed variances in the expression of seven immune cells and 15 immune-correlated pathways between the two risk groups. Furthermore, our results confirmed the ceRNA network associated with the intermittent hypoxia-related lncRNA GSEC/miR-873-3p/EGLN3 regulatory pathway. GSEC showed pronounced expression in lung adenocarcinoma tissues and specific cell lines, and its inhibition resulted in reduced proliferation and migration in A549 and PC9 cells. Intriguingly, GSEC manifested oncogenic properties by sponging miR-873-3p and demonstrated a tendency to modulate EGLN3 expression favorably.

Conclusion: GSEC acts as an oncogenic lncRNA by interacting with miR-873-3p, modulating EGLN3 expression. This observation underscores the potential of GSEC as a diagnostic and therapeutic target for LUAD.

Keywords: EGLN3; GSEC; Immune microenvironment; Intermittent hypoxia; Lung adenocarcinoma; MiR-873-3p.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma*
Humans
Hypoxia
Hypoxia-Inducible Factor-Proline Dioxygenases
Lung
MicroRNAs* / genetics
Prognosis
RNA, Long Noncoding* / genetics
Reproducibility of Results
Tumor Microenvironment / genetics

Substances

RNA, Long Noncoding
MicroRNAs
EGLN3 protein, human
Hypoxia-Inducible Factor-Proline Dioxygenases
MIRN873 microRNA, human

Grants and funding

This research was supported by the National Natural Science Foundation of China (No. 81970082). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.