Cancer Management and Research (Oct 2020)

DUS4L Silencing Suppresses Cell Proliferation and Promotes Apoptosis in Human Lung Adenocarcinoma Cell Line A549

  • Li Z,
  • Yin C,
  • Li B,
  • Yu QY,
  • Mao WJ,
  • Li J,
  • Lin JP,
  • Meng YQ,
  • Feng HM,
  • Jing T

Journal volume & issue
Vol. Volume 12
pp. 9905 – 9913

Abstract

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Zheng Li,* Ci Yin,* Bin Li, Qi-Yao Yu, Wen-Jie Mao, Jie Li, Jun-Ping Lin, Yu-Qi Meng, Hai-Ming Feng, Tao Jing Department of Thoracic Surgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou 730030, China*These authors contributed equally to this workCorrespondence: Bin LiDepartment of Thoracic Surgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou 730030, ChinaTel/Fax +86 931 8942073Email [email protected]: This study aims to investigate the potential role of DUS4L (dihydrouridine synthase 4 like) in lung adenocarcinoma (LUAD) and explore its associated pathways in human LUAD.Methods: Firstly, we evaluated the relationships between clinicopathological characteristics and DUS4L expression via analysis of TCGA RNA sequencing data and other publicly available databases. Then, DUS4L was effectively silenced in LUAD cell line A549 using the lentiviral shRNA (short-hairpin RNA) transfection to assess its effects on cell proliferation, cycle and apoptosis in LUAD cells. RNA-seq technology was applied to shDUS4L and shCtrl-transfected cells to generate the corresponding gene expression profiles. Differentially expressed genes (DEGs) were identified using the DESeq2 program package. Also, DEGs were subjected to Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis to explore the associated molecular signaling pathways and relevant biological functions.Results: Analysis of TCGA data revealed that DUS4L was highly upregulated in LUAD tissues which was related to clinical T and TNM stages of LUAD. The knockdown of DUS4L effectively inhibited cell proliferation and promoted apoptosis in A549 cells. Furthermore, the DEGs between the shDUS4L and shCtrl A549 cells were mainly enriched in biological processes associated with spliceosome, ribosome, RNA catabolic process, ncRNA (non-coding RNA) processing, and p53 signaling pathway.Conclusion: Altogether, our results suggest that DUS4L is significantly associated with tumorigenesis and could be utilized as a novel biomarker and therapeutic target for LUAD.Keywords: DUS4L, lung adenocarcinoma, proliferation, apoptosis, TCGA

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