Abstract
As novel master regulators of initiation and progression, long non-coding RNAs (lncRNAs) can response to therapy in a wide variety of malignances. This study aimed to explore the regulatory mechanisms in non-small cell lung cancer (NSCLC) by constructing lncRNA-miRNA-mRNA networks. The whole transcriptome sequence was performed in five NSCLC tissues and their corresponding paired adjacent normal tissues. MicroRNAs (miRNAs) and mRNAs expression profiles were obtained from TCGA database. “EdgeR” R package was used for gene expression comparisons and the genes with | log2FC |> 2 and false discovery rate (FDR) adjusted P<0.05 were considered significant. Totally, 559 differentially expressed lncRNAs (DELs) (235 up-regulated, 324 down-regulated) were identified via whole transcriptome sequence analysis. Subsequently, 14 up-regulated lncRNAs were obtained in the intersection of our RNA-seq data and TCGA dataset. The dysregulations of the selected lncRNAs were evaluated through GEPIA. Three candidate lncRNAs (LINC01426, TYMSOS, VPS9D1-AS1) were finally selected for further study. Through bioinformatics prediction, with the three lnRNAs and their associated miRNAs (n=14) and mRNAs (n=218), a lncRNA-miRNA-mRNA network was constructed. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway associated with the targeted genes were proceeded. In addition, the protein–protein interaction (PPI) network construction was performed by STRING and lncRNA-miRNA-mRNA regulatory network was visualized via Cytoscape. The top ten significant hub-genes in the PPI network are identified based on their node degrees. Moreover, the lncRNA-miRNA and miRNA-mRNA interactions were predicted using the StarBase and survival analyses were performed in Kaplan-Meier plotter website. We concluded that TYMSOS/hsa-miR-101-3p/CEP55 and TYMSOS/hsa-miR-195-5p/CHEK1 ceRNA regulatory aixs may play vital roles in the occurrence and development of NSCLC, and may provide novel therapeutic targets in the future.
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Abbreviations
- LncRNA:
-
Long noncoding RNA
- NSCLC:
-
Non-small cell lung cancer
- TCGA:
-
The cancer genome atlas
- PPI:
-
Protein–protein interaction
- GO:
-
Gene ontology
- KEGG:
-
Kyoto encyclopedia of genes and genomes
- DELs:
-
Differentially expressed lncRNAs
- LUAD:
-
Adenocarcinoma
- LUSC:
-
Squamous cell carcinoma
- SCLC:
-
Small cell carcinoma
- mRNA:
-
Messenger RNA
- ceRNA:
-
Competing endogenous RNA
- FC:
-
Fold change
- DEMIs:
-
Differentially expressed miRNAs
- DEMs:
-
Differentially expressed mRNAs
- STRING:
-
The search tool for the retrieval of interacting genes database
- RNA-seq:
-
RNA sequencing
- BP:
-
Biological processes
- CC:
-
Cellular components
- MF:
-
Molecular functions
- MCODE:
-
Molecular complex detection
- OS:
-
Overall survival
- MREs:
-
MiRNA response elements
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Acknowledgements
The authors gratefully acknowledge Henan Key Laboratory of Pharmacology for Liver Diseases for providing experimental platform support.
Funding
This work was supported by the Leading Talents of Science and Technology Innovation in Henan Province (Grant Number 20420051008), the Key Project of Discipline Construction of Zhengzhou University (Grant Number XKZDQY202009).
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LD and LJ were responsible for the conception and design of the research, and drafting the manuscript. TY and JL performed the data acquisition. ML and JL performed the data analysis and interpretation. QS and YW performed the statistical analysis. All authors read and approved the final manuscript.
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10528_2022_10299_MOESM1_ESM.tif
Supplementary file1 (TIF 2649 kb)—Fig. 1 PPI network of the DEMs in the ceRNA network. The circles represent genes, and the lines represent interactions between the proteins encoded by the genes
10528_2022_10299_MOESM2_ESM.tif
Supplementary file2 (TIF 20556 kb)—Fig. 2 Potential binding sites for TYMSOS, LINC01426 and VPS9D1-AS1 to their targeted miRNA, respectively
10528_2022_10299_MOESM3_ESM.tif
Supplementary file3 (TIF 1624 kb)—Fig. 3 Expression analysis of remaining eight hub genes based on TCGA database by GEPIA. A. Boxplots depicting the expression levels of NUF2 in LUAD and LUSC. B. Boxplots depicting the expression levels of NCAPH in LUAD and LUSC. C. Boxplots depicting the expression levels of EXO1 in LUAD and LUSC. D. Boxplots depicting the expression levels of MAD2L1 in LUAD and LUSC. E. Boxplots depicting the expression levels of KIF20A in LUAD and LUSC. F. Boxplots depicting the expression levels of TPX2 in LUAD and LUSC. G. Boxplots depicting the expression levels of CDK1in LUAD and LUSC. H. Boxplots depicting the expression levels of SHCBP1 in LUAD and LUSC
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Ji, L., Yang, T., Liu, M. et al. Construction of lncRNA TYMSOS/hsa-miR-101-3p/CEP55 and TYMSOS/hsa-miR-195-5p/CHEK1 Axis in Non-small Cell Lung Cancer. Biochem Genet 61, 995–1014 (2023). https://doi.org/10.1007/s10528-022-10299-0
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DOI: https://doi.org/10.1007/s10528-022-10299-0