RNA sequencing and bioinformatics analysis reveals the downregulation of DNA replication genes by morindone in colorectal cancer cells
Document Type
Article
Publication Date
6-1-2024
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.
Keywords
Anthraquinone, Colorectal cancer, Morinda citrifolia L, Morindone, RNA sequencing
Divisions
molecular,CHEMISTRY,pharchemistry
Funders
Universiti Malaya [Grant no. IIRG003A-2019, IIRG003C-2019]
Publication Title
Applied Biochemistry and Biotechnology
Volume
196
Issue
6
Publisher
Springer
Publisher Location
ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES