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RNA Sequencing and Bioinformatics Analysis Reveals the Downregulation of DNA Replication Genes by Morindone in

Cheok Wui Chee1, Najihah Mohd Hashim2,3,4, Iskandar Abdullah4,5

  • 1Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.

Applied Biochemistry and Biotechnology
|August 29, 2023
PubMed

Insights

Morindone shows potential against colorectal cancer (CRC) by downregulating key DNA replication genes. This study identifies GINS2 as a promising therapeutic target for CRC treatment.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Morindone, a natural anthraquinone, exhibits pharmacological properties in various cancers.
  • Anticancer effects and molecular mechanisms of morindone in colorectal cancer (CRC) are not well understood.

Purpose of the Study:

  • To investigate the anticancer effects of morindone in colorectal cancer (CRC) cell lines.
  • To elucidate the molecular mechanisms underlying morindone's action in CRC using RNA sequencing.

Main Methods:

  • RNA sequencing was employed to identify differentially expressed genes (DEGs) in HCT116 and HT29 CRC cells after morindone treatment.
  • Functional enrichment analysis (Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes) was performed on overlapping DEGs.
  • Seven hub genes were identified and validated using reverse transcription quantitative polymerase chain reaction (rt-qPCR).

Main Results:

  • Morindone treatment led to the downregulation of seven hub genes (MCM5, MCM6, MCM10, GINS2, POLE2, PRIM1, WDHD1) involved in DNA replication.
  • The most significant functional enrichments included negative regulation of cell development and the MAPK signaling pathway.
  • GINS2 was identified as the most cancer-dependent gene, correlating with better survival outcomes in both cell lines.

Conclusions:

  • Morindone demonstrates potential therapeutic benefits for colorectal cancer (CRC).
  • The study identifies key DNA replication genes, particularly GINS2, as potential pharmacological targets for morindone-based CRC therapy.
  • Findings provide a foundation for further investigation into morindone as a CRC treatment.
Keywords:
Morinda citrifolia L.AnthraquinoneColorectal cancerMorindoneRNA sequencing

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