Construction and analysis of the ceRNA network hsa_circ_0031968/miR-3611/GCG in lung adenocarcinoma

Yang Yang; Yuan Zhang; Xuqing Ding; Yukai Ren; Bochong Wei; Zongxiang Lin; Yunfei Nie; Yuxia Fan

doi:10.21037/atm-21-5854

Construction and analysis of the ceRNA network hsa_circ_0031968/miR-3611/GCG in lung adenocarcinoma

Ann Transl Med. 2021 Dec;9(24):1757. doi: 10.21037/atm-21-5854.

Authors

Yang Yang^#¹, Yuan Zhang^#¹, Xuqing Ding^#², Yukai Ren¹, Bochong Wei¹, Zongxiang Lin¹, Yunfei Nie¹, Yuxia Fan³

Affiliations

¹ Department of Thoracic Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
² Department of Thoracic Surgery, Nanyang Second General Hospital, Nanyang, China.
³ Department of Thyroid Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.

^# Contributed equally.

Abstract

Background: A competitive endogenous RNA (ceRNA) network was constructed to examine the potential mechanisms of circular RNAs (circRNAs) in lung adenocarcinoma (LUAD).

Methods: LUAD-related data sets were obtained from the Gene Expression Omnibus (GEO) database and screened for differentially expressed circRNAs (DECs) and differentially expressed microRNAs (DEMs). We identified the target microRNAs (miRNAs) regulated by the DECs and the potential target genes of the miRNA. The basic structure of the DECs were analyzed and enrichment analyses were conducted to determine the function of the circRNA. The Kaplan-Meier method for survival analysis was used to examine the clinical data from The Cancer Genome Atlas (TCGA) database. A protein-protein interaction (PPI) network was constructed to determine the hub genes. The relative expression of the RNA molecules on the ceRNA axis was verified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis.

Results: A total of 17 DECs and 237 DEMs were selected for analysis. After reviewing the cancer-specific circRNA database (CSCD), 10 circRNAs were identified. The 432 target miRNAs were screened by circRNA interactome (CRI) and cross-referenced with the DEMs to obtain 126 miRNAs of interest. The expression of miR-3611, which is regulated by hsa_circ_0031968, was found to significantly affect the survival and prognosis of patients with LUAD (P≤0.05). The target gene function of hsa_circ_0031968 was determined to be mainly enriched in SMAD binding, and the signaling pathway was primarily enriched in miRNAs related to cancer. The TCGA database screened out 2,484 differentially expressed mRNAs (DEmRNAs) and intersection analysis with the target gene of miR-3611 revealed 1 gene, namely the proglucagon gene (GCG). Therefore, we chose the hsa_circ_0031968/miR-3611/GCG axis for further research. The expression of GCG was determined to be associated with a poorer survival rate and higher T stage in LUAD patients. Finally, 17 hub genes that interact with GCG were identified.

Conclusions: The ceRNA regulatory network hsa_circ_0031968/miR-3611/GCG was successfully constructed and this provided novel insights into the identification of biomarkers and the pathogenesis of LUAD. This knowledge will contribute to the early diagnosis and development of potential treatment for patients with LUAD.

Keywords: Lung adenocarcinoma (LUAD); circular RNA (circRNA); competitive endogenous RNA network (ceRNA network); microRNA (miRNA).