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LncRNA THOR acts as a retinoblastoma promoter through enhancing the combination of c-myc mRNA and IGF2BP1 protein

2018; Elsevier BV; Volume: 106; Linguagem: Inglês

10.1016/j.biopha.2018.07.052

1950-6007

Yamin Shang,

Viral-associated cancers and disorders

Long non-coding RNA (lncRNA) THOR is an extremely conserved lncRNA with specifically expressed in testis while widespreadly exist in human multiple cancer tissues. The high expression of it significantly promotes the occurrence and progression of melanoma, non-small cell lung cancer, osteosarcoma and renal cell carcinoma. However, the expression pattern and effects of lncRNA THOR in the progression of retinoblastoma remain unclear. As a result, this study was conducted to discovery the expression and roles of lncRNA THOR in the malignant phenotype transformation of retinoblastoma cells, as well as its underlying mechanism. Our results demonstrated that lncRNA THOR was over-expressed in the retina tissues from retinoblastoma patients and retinoblastoma Y79 and WERI-Rb1 cell lines. Down-regulation of lncRNA THOR with siRNA significantly repressed cell growth, migration and S phase accumulation, while induced cell apoptosis and G1 phase reduction and reduced the expression of c-myc. Besides, knockdown of c-myc promoted cell apoptosis and suppressed cell proliferation. Furthermore, RNA pull down and PIP assays showed that up-regulation of lncRNA THOR enhanced the combination of IGF2BP1 protein and c-myc RNA. And lncRNA THOR up-regulation obviously increased the tumorigenesis of Y79 cells in vivo. In conclusion, this study makes clear that lncRNA THOR is up-regulated in retinoblastoma, and its over-expression significantly enhances the malignant phenotype transformation of retinoblastoma cells through up-regulating c-myc expression via enhancing its combination with TGF2BP1 protein. Overall, our study illustrates that lncRNA THOR/c-myc molecular cascade might be another potent target for retinoblastoma treatment.