Circulating miR-1246 Targeting UBE2C, TNNI3, TRAIP, UCHL1 Genes and Key Pathways as a Potential Biomarker for Lung Adenocarcinoma: Integrated Biological Network Analysis

Siyuan Huang; Yong-Kai Wei; Satyavani Kaliamurthi; Yanghui Cao; Asma Sindhoo Nangraj; Xin Sui; Dan Chu; Huan Wang; Dong-Qing Wei; Gilles H Peslherbe; Gurudeeban Selvaraj; Jiang Shi

doi:10.3390/jpm10040162

Circulating miR-1246 Targeting UBE2C, TNNI3, TRAIP, UCHL1 Genes and Key Pathways as a Potential Biomarker for Lung Adenocarcinoma: Integrated Biological Network Analysis

J Pers Med. 2020 Oct 11;10(4):162. doi: 10.3390/jpm10040162.

Authors

Siyuan Huang¹, Yong-Kai Wei², Satyavani Kaliamurthi^{3

4}, Yanghui Cao⁵, Asma Sindhoo Nangraj⁶, Xin Sui¹, Dan Chu⁷, Huan Wang⁷, Dong-Qing Wei^{3

4

6}, Gilles H Peslherbe³, Gurudeeban Selvaraj^{3

4}, Jiang Shi⁷

Affiliations

¹ Department of Oncology 2, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou 450052, China.
² College of Science, Henan University of Technology, Zhengzhou 450001, China.
³ Centre for Research in Molecular Modeling and Department of Chemistry and Biochemistry, Concordia University, 7141 Sherbrooke Street West, Montréal, QC H4B 1R6, Canada.
⁴ Center of Interdisciplinary Science-Computational Life Sciences, College of Biological Engineering, Henan University of Technology, No.100, Lianhua Street, Hi-Tech Development Zone, Zhengzhou 450001, China.
⁵ Department of General Surgery, Henan Tumor Hospital, No.127 Dongming Road, Zhengzhou 450008, China.
⁶ The State Key Laboratory of Microbial Metabolism, College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
⁷ Department of Respiratory, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou 450052, China.

Abstract

Analysis of circulating miRNAs (cmiRNAs) before surgical operation (BSO) and after the surgical operation (ASO) has been informative for lung adenocarcinoma (LUAD) diagnosis, progression, and outcomes of treatment. Thus, we performed a biological network analysis to identify the potential target genes (PTGs) of the overexpressed cmiRNA signatures from LUAD samples that had undergone surgical therapy. Differential expression (DE) analysis of microarray datasets, including cmiRNAs (GSE137140) and cmRNAs (GSE69732), was conducted using the Limma package. cmiR-1246 was predicted as a significantly upregulated cmiRNA of LUAD samples BSO and ASO. Then, 9802 miR-1246 target genes (TGs) were predicted using 12 TG prediction platforms (MiRWalk, miRDB, and TargetScan). Briefly, 425 highly expressed overlapping miRNA-1246 TGs were observed between the prediction platform and the cmiRNA dataset. ClueGO predicted cell projection morphogenesis, chemosensory behavior, and glycosaminoglycan binding, and the PI3K-Akt signaling pathways were enriched metabolic interactions regulating miRNA-1245 overlapping TGs in LUAD. Using 425 overlapping miR-1246 TGs, a protein-protein interaction network was constructed. Then, 12 PTGs of three different Walktrap modules were identified; among them, ubiquitin-conjugating enzyme E2C (UBE2C), troponin T1(TNNT1), T-cell receptor alpha locus interacting protein (TRAIP), and ubiquitin c-terminal hydrolase L1(UCHL1) were positively correlated with miR-1246, and the high expression of these genes was associated with better overall survival of LUAD. We conclude that PTGs of cmiRNA-1246 and key pathways, namely, ubiquitin-mediated proteolysis, glycosaminoglycan binding, the DNA metabolic process, and the PI3K-Akt-mTOR signaling pathway, the neurotrophin and cardiomyopathy signaling pathway, and the MAPK signaling pathway provide new insights on a noninvasive prognostic biomarker for LUAD.

Keywords: PI3K–Akt signaling pathways; TargetScan; UBE2C; circulating miR-1246; glycosaminoglycan binding; lung adenocarcinoma; prognosis.