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.
Cornelia de Lange syndrome (CdLS) is a dominant multisystemic malformation syndrome due to mutations in five genes-NIPBL, SMC1A, HDAC8, SMC3, and RAD21. The characteristic facial dysmorphisms include microcephaly, arched eyebrows, synophrys, short nose with depressed bridge and anteverted nares, long philtrum, thin lips, micrognathia, and hypertrichosis. Most affected individuals have intellectual disability, growth deficiency, and upper limb anomalies. This study looked at individuals from diverse populations with both clinical and molecularly confirmed diagnoses of CdLS by facial analysis technology. Clinical data and images from 246 individuals with CdLS were obtained from 15 countries. This cohort included 49% female patients and ages ranged from infancy to 37 years. Individuals were grouped into ancestry categories of African descent, Asian, Latin American, Middle Eastern, and Caucasian. Across these populations, 14 features showed a statistically significant difference. The most common facial features found in all ancestry groups included synophrys, short nose with anteverted nares, and a long philtrum with thin vermillion of the upper lip. Using facial analysis technology we compared 246 individuals with CdLS to 246 gender/age matched controls and found that sensitivity was equal or greater than 95% for all groups. Specificity was equal or greater than 91%. In conclusion, we present consistent clinical findings from global populations with CdLS while demonstrating how facial analysis technology can be a tool to support accurate diagnoses in the clinical setting. This work, along with prior studies in this arena, will assist in earlier detection, recognition, and treatment of CdLS worldwide.