AURKB, CHEK1 and NEK2 as the Potential Target Proteins of Scutellaria barbata on Hepatocellular Carcinoma: An Integrated Bioinformatics Analysis

Chaoyuan Huang; Hu Luo; Yuancheng Huang; Chongkai Fang; Lina Zhao; Peiwu Li; Chong Zhong; Fengbin Liu

doi:10.2147/IJGM.S318077

AURKB, CHEK1 and NEK2 as the Potential Target Proteins of Scutellaria barbata on Hepatocellular Carcinoma: An Integrated Bioinformatics Analysis

Int J Gen Med. 2021 Jul 12:14:3295-3312. doi: 10.2147/IJGM.S318077. eCollection 2021.

Authors

Chaoyuan Huang¹, Hu Luo¹, Yuancheng Huang¹, Chongkai Fang¹, Lina Zhao², Peiwu Li², Chong Zhong³, Fengbin Liu^{2

4}

Affiliations

¹ The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.
² Department of gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.
³ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.
⁴ Department of gastroenterology, Baiyun Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.

Abstract

Objective: We aim to explore the potential anti-HCC mechanism of Scutellaria barbata through integrated bioinformatics analysis.

Methods: We searched active ingredients and related targets of Scutellaria barbata via TCMSP database, PubChem and SwissTargetPrediction database. Then, we identified HCC disease targets from GEO dataset by WGCNA. Next, the intersected targets of disease targets and drug targets were input into STRING database to construct PPI networking in order to obtain potential therapeutic targets of Scutellaria barbata. Cytoscape software was used to carry out network topology analysis of potential targets. We used the R package for GO analysis and KEGG analysis. Finally, we used AutoDock vina and PyMOL software for molecular docking.

Results: Sixteen active components from Scutellaria barbata were lastly selected for further investigation. A total of 442 component targets were identified from 16 active ingredients of Scutellaria barbata after the removal of duplicate targets. GSE45436 was selected for construction of WGCNA and screening of differentially expressed genes. A total of 354 genes were up-regulated in HCC samples and 100 were down-regulated in HCC patients. Twenty-one common genes were obtained by intersection and 10 critical targets were filtered for further investigation. The enrichment analysis showed that cell cycle, DNA replication, p53 signaling pathway were mainly involved. The molecular docking results showed that 4 potential combinations were with the best binding energy and molecular interactions.

Conclusion: AURKB, CHEK1 and NEK2 could be the potential target proteins of Scutellaria barbata in treating HCC. Cell cycle, DNA replication, p53 signaling pathway consist of the fundamental regulation cores in this mechanism.

Keywords: Scutellaria barbata; bioinformatics analysis; effector mechanism; hepatocellular carcinoma; molecular docking; network pharmacology.

Grants and funding

This work was supported by National Natural Science Foundation of China (81873303), Natural Science Foundation of Guangdong Province, China (2019A1515011013), Key Projects of Educational Commission of Guangdong Province, China (2019KZDXM045), Administration of Traditional Chinese Medicine of Guangdong Province, China (20211122), and Medical innovation project of the First Affiliated Hospital of Guangzhou University of Chinese Medicine (2019IIT18), Guangzhou University of Chinese Medicine first-class discipline Construction Research Key Project (A1-AFD018181A27); Guangdong Famous Traditional Chinese Medicine Doctor Inheritance Studio of Fengbin Liu (Guangdong Traditional Chinese Medicine Office [2020] No. 1).