RNA sequencing and bioinformatics analysis reveals the downregulation of DNA replication genes by morindone in colorectal cancer cells

Chee, Cheok Wui and Mohd Hashim, Najihah and Abdullah, Iskandar and Nor Rashid, Nurshamimi (2024) RNA sequencing and bioinformatics analysis reveals the downregulation of DNA replication genes by morindone in colorectal cancer cells. Applied Biochemistry and Biotechnology, 196 (6). pp. 3216-3233. ISSN 0273-2289, DOI https://doi.org/10.1007/s12010-023-04690-9.

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Abstract

Morindone, a natural anthraquinone compound, has been reported to have significant pharmacological properties in different cancers. However, its anticancer effects in colorectal cancer (CRC) and the underlying molecular mechanisms remain obscure. In this study, RNA sequencing was used to assess the differentially expressed genes (DEGs) following morindone treatment in two CRC cell lines, HCT116 and HT29 cells. Functional enrichment analysis of overlapping DEGs revealed that negative regulation of cell development from biological processes and the MAPK signalling pathway were the most significant Gene Ontology terms and Kyoto Encyclopaedia of Genes and Genome pathway, respectively. Seven hub genes were identified among the overlapping genes, including MCM5, MCM6, MCM10, GINS2, POLE2, PRIM1, and WDHD1. All hub genes were found downregulated and involved in DNA replication fork. Among these, GINS2 was identified as the most cancer-dependent gene in both cells with better survival outcomes. Validation was performed on seven hub genes with rt-qPCR, and the results were consistent with the RNA sequencing findings. Collectively, this study provides corroboration of the potential therapeutic benefits and suitable pharmacological targets of morindone in the treatment of CRC.

Item Type: Article
Funders: Universiti Malaya [Grant no. IIRG003A-2019, IIRG003C-2019]
Uncontrolled Keywords: Anthraquinone; Colorectal cancer; Morinda citrifolia L; Morindone; RNA sequencing
Subjects: Q Science > QD Chemistry
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Medicine > Department of Molecular Medicine
Faculty of Science > Department of Chemistry
Faculty of Pharmacy > Department of Pharmaceutical Chemistry
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 18 Jul 2024 08:14
Last Modified: 18 Jul 2024 08:14
URI: http://eprints.um.edu.my/id/eprint/46016

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