Investigation of Key Signaling Pathways Associating miR-204 and Common Retinopathies

Abstract

MicroRNAs are a large group of small noncoding RNAs that work in multiple cellular pathways. miR-204, as one of the key axes in the development, maintenance, and pathogenesis of the retina, plays several roles by modulating its target genes. This study was aimed at evaluating the target genes of miR-204 involved in the development and progression of common retinopathies such as glaucoma, retinoblastoma, and age-related macular degeneration. In this study, three datasets related to retinopathies (GSE50195, GSE27276, and GSE97508) were selected from Gene Expression Omnibus. miR-204 target genes were isolated from TargeScan. The shares between retinopathy and miR-204 target genes were then categorized. Using Enrichr and STRING, we highlighted the signaling pathways and the relationships between the proteins. SHC1 events in ERBB2, adherent junction’s interactions, NGF signaling via TRKA from the plasma membrane, IRF3-mediated activation of type 1 IFN, pathways in upregulated genes and G0 and early G1, RORA-activated gene expression, PERK-regulated gene expression, adherent junction’s interactions, and CREB phosphorylation pathways in downregulated genes were identified in glaucoma, retinoblastoma, and age-related macular degeneration. WEE1, SMC2, HMGB1, RRM2, and POLA1 proteins were also observed to be involved in the progression and invasion of retinoblastoma; SLC24A2 and DTX4 in age-related macular degeneration; and EPHB6, EFNB3, and SHC1 in glaucoma. Continuous bioinformatics analysis has shown that miR-204 has a significant presence and expression in retinal tissue, and approximately 293 genes are controlled and regulated by miR-204 in this tissue; also, target genes of miR-204 have the potential to develop various retinopathies; thus, a study of related target genes can provide appropriate treatment strategies in the future.

Exosomal MicroRNA Profiling in Vitreous Humor Derived From Pathological Myopia Patients

“…In this way, miR-204 performs critical functions during retinal development and maintenance. 28 , 29 The aberration of miR-204 may reflect the irreversible changes of the retina.…”

Retinoblastoma: Review and new insights

“…Patients with Rb have survival rates higher than 95-98% in industrialized countries but mortality remains high in developing countries ( 2 , 4 , 12 ). For example, the mortality rate in Africa is 70% ( 44 ).…”

“…This increase in proliferation is linked to the miR-17 sub-family, which targets cell-cycle inhibitors p21 and p57 ( 43 ). miR-204 acts as a tumor suppressor, while it has much less expression in patients with retinoblastoma ( 44 ). Cyclin-D2 and MMP-9 are two key genes that are regulated by miR-204 in retinoblastoma.…”

“…Cyclin-D2 and MMP-9 are two key genes that are regulated by miR-204 in retinoblastoma. High expression of cyclin-D2 and MMP-9 increases the cell division rate and progression of RB ( 44 ). miR-17-3P, miR-17-5P, miR-18a, and miR-20a are highly expressed in the serum of children with Rb ( 45 ).…”

The clinical diagnostic value of plasma miR-592 and miR-217-3p levels in retinoblastoma

“…For example, the expression of miR-204 in Rb patients is dysregulated, and its expression level is related to optic nerve infiltration, lymph node metastasis, and tumour tissue differentiation. miR-204 may affect the proliferation and apoptosis of Rb cells, thereby affecting the development of Rb, which may become an early stage molecular indicator for diagnosing and evaluating the prognosis of Rb (43)(44)(45); miR-338-5p is up-regulated in the serum of patients with Rb, which may play a role in promoting cancer in the occurrence and development of Rb, and has the potential value of the early diagnosis of Rb (46,47). Recent studies have shown that dysregulated miR-592 and miR-217-3p have been reported to be involved in developing many different types of cancer.…”