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. 2020 Mar;121(3):2690-2703.
doi: 10.1002/jcb.29489. Epub 2019 Nov 6.

Identification of key microRNAs and hub genes in non-small-cell lung cancer using integrative bioinformatics and functional analyses

Feifeng Song  1 , Zixue Xuan  1 , Xiuli Yang  1 , Xiaolan Ye  1 , Zongfu Pan  1 , Qingxia Fang  1
Affiliations

Identification of key microRNAs and hub genes in non-small-cell lung cancer using integrative bioinformatics and functional analyses

Feifeng Song et al. J Cell Biochem. 2020 Mar.

Abstract

Non-small-cell lung cancer (NSCLC) is an extremely debilitating respiratory malignancy. However, the pathogenesis of NSCLC has not been fully clarified. The main objective of our study was to identify potential microRNAs (miRNAs) and their regulatory mechanism in NSCLC. Using a systematic review, two NSCLC-associated miRNA data sets (GSE102286 and GSE56036) were obtained from Gene Expression Omnibus, and the differentially expressed miRNAs (DE-miRNAs) were accessed by GEO2R. Survival analysis of candidate DE-miRNAs was conducted using the Kaplan-Meier plotter database. To further illustrate the roles of DE-miRNAs in NSCLC, their potential target genes were predicted by miRNet and were annotated by the Database for Annotation, Visualization and Integrated Discovery (DAVID) program. Moreover, the protein-protein interaction (PPI) and miRNA-hub gene regulatory network were established using the STRING database and Cytoscape software. The function of DE-miRNAs in NSCLC cells was evaluated by transwell assay. Compared with normal tissues, a total of eight DE-miRNAs was commonly changed in two data sets. The survival analysis showed that six miRNAs (miR-21-5p, miR-31-5p, miR-708-5p, miR-30a-5p, miR-451a, and miR-126-3p) were significantly correlated with overall survival. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that target genes of upregulated miRNAs were enriched in pathways in cancer, microRNAs in cancer and proteoglycans in cancer, while the target genes of downregulated miRNAs were mainly associated with pathways in cancer, the PI3K-Akt signaling pathway and HTLV-I infection. Based on the miRNA-hub gene network and expression analysis, PTEN, EGFR, STAT3, RHOA, VEGFA, TP53, CTNNB1, and KRAS were identified as potential target genes. Furthermore, all six miRNAs exhibited significant effects on NSCLC cell invasion. These findings indicate that six DE-miRNAs and their target genes may play important roles in the pathogenesis of NSCLC, which will provide novel information for NSCLC treatments.

Keywords: bioinformatics analysis; differentially expressed microRNAs; hub genes; non-small-cell lung cancer; pathways.

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References

REFERENCES

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca-Cancer J Clin. 2018;68(6):394-424. https://doi.org/10.3322/caac.21492 https://www.ncbi.nlm.nih.gov/pubmed/30207593
    1. Chen W, Sun K, Zheng R, et al. Cancer incidence and mortality in China, 2014. Chin J Cancer Res. 2018;30(1):1-12. https://doi.org/10.21147/j.issn.1000-9604.2018.01.01 https://www.ncbi.nlm.nih.gov/pubmed/29545714
    1. Oser MG, Niederst MJ, Sequist LV, Engelman JA. Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin. Lancet Oncol. 2015;16(4):E165-E172. https://doi.org/10.1016/S1470-2045(14)71180-5 https://www.ncbi.nlm.nih.gov/pubmed/25846096
    1. Vergnenegre A, Chouaid C. Review of economic analyses of treatment for non-small-cell lung cancer (NSCLC). Exp Rev Pharmacoecon Outcomes Res. 2018;18(5):519-528. https://doi.org/10.1080/14737167.2018.1485099 https://www.ncbi.nlm.nih.gov/pubmed/29869900
    1. Iqbal MA, Arora S, Prakasam G, Calin GA, Syed MA. MicroRNA in lung cancer: role, mechanisms, pathways and therapeutic relevance. Mol Aspects Med. 2018:1-17. https://doi.org/10.1016/j.mam.2018.07.003 https://www.ncbi.nlm.nih.gov/pubmed/30102929.

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