Transcriptome Sequencing Reveals Tgf-ß-Mediated Noncoding RNA Regulatory Mechanisms Involved in DNA Damage in the 661W Photoreceptor Cell Line.

Transforming growth factor ß (Tgf-ß), a pleiotropic cytokine, can enhance DNA repair in various cells, including cancer cells and neurons. The noncoding regulatory system plays an important role in Tgf-ß-mediated biological activities, whereas few studies have explored its role in DNA damage and repair. In this study, we suggested that Tgf-ß improved while its inhibitor LSKL impaired DNA repair and cell viability in UV-irradiated 661W cells. Moreover, RNA-seq was carried out, and a total of 106 differentially expressed (DE)-mRNAs and 7 DE-lncRNAs were identified between UV/LSKL and UV/ctrl 661W cells. Gene ontology and Reactome analysis confirmed that the DE-mRNAs were enriched in multiple DNA damaged- and repair-related biological functions and pathways. We then constructed a ceRNA network that included 3 lncRNAs, 19 miRNAs, and 29 mRNAs with a bioinformatics prediction. Through RT-qPCR and further functional verification, 2 Tgf-ß-mediated ceRNA axes (Gm20559-miR-361-5p-Oas2/Gbp7) were further identified. Gm20559 knockout or miR-361-5p mimics markedly impaired DNA repair and cell viability in UV-irradiated 661W cells, which confirms the bioinformatics results. In summary, this study revealed that Tgf-ß could reduce DNA damage in 661W cells, provided a Tgf-ß-associated ceRNA network for DNA damage and repair, and suggested that the molecular signatures may be useful candidates as targets of treatment for photoreceptor pathology.