• Rs94142948 modulates the neurodegeneration signaling pathway by regulating the expression level of FAM90A in the retinoblastoma patients: integrated systems biology and bioinformatics investigation
  • Saba Hojjati,1,* Mohammad Rezaei,2


  • Introduction: Retinoblastoma is a rare type of eye cancer that usually develops in early childhood, typically before the age of 5. This form of cancer develops in the retina, which is the specialized light-sensitive tissue at the back of the eye that detects light and color.In children with retinoblastoma, the disease often affects only one eye. However, one out of three children with retinoblastoma develops cancer in both eyes. The most common first sign of retinoblastoma is a visible whiteness in the pupil called "cat's eye reflex" or leukocoria . Retinoblastoma is diagnosed in 250 to 350 children per year in the United States. It accounts for about 4 percent of all cancers in children younger than 15 years.
  • Methods: First of all, GSE208143 raw data was selected from Gene Expression Omnibus (GEO) and analyze by R studio to obtain differentially expressed genes(DEGs). The limma package was used for the statistical analyses and finding the novel DEGs. Protein-protein interaction analysis was performed by STRING online software. Pathway enrichment analysis was performed by ENRICHR. Single nucleotide polymorphism (SNP) analysis was performed by miRNASNP v3.
  • Results: Based on the microarray analysis, FAM90A1 (logFC: 4.37 , adj. P. Val: 8.942507e-05 ) has a significant uo-regulation in the retinoblastoma patients, compared to control. ALG1, USP31, RFPL4A, ZNF329, FAM90a26, and ZNF195 has a significant protein interaction with FAM90A1. Based on the pathway enrichment analysis, FAM90A1 and its interactome has a significant contribution in the regulation of Endocytosis and Pathways of neurodegeneration signaling pathway. miRNASNP analysis revealed that rs941412948 (A/G) regulates the expression level of FAM90A1 by reducing the binding affinity of hsa-miR-7-2-3P, hsa- miR-495-3P, hsa-miR-5688, hsa-miR-1323, hsa-miR-5480-3P, hsa-miR-7-1-3P, and hsa-miR-607 miRNAs to this mRNA. miRWalk online database validates the interaction of mentioned microRNAs with FAM90A1.
  • Conclusion: Rs941412948 has a significant novel role in the modulating the Endocytosis and Pathways of neurodegeneration signaling pathway by regulating the expression level of FAM90A1 in the retinoblastoma patients. Mentioned region of DNA could be a novel therapeutic target for the prognosis, diagnosis, and possible treatment strategies for retinoblastoma patients.
  • Keywords: Systems biology, Bioinformatics, Retinoblastoma, Nervous system, Network analysis