LncRNA CCAT1 sponges miR-218-5p to promote EMT, cellular migration and invasion of retinoblastoma by targeting MTF2

Retinoblastoma (RB) is the primary neoplasms of the retina that is most common in pediatrics age. Long non coding RNAs (lncRNAs) has been noticed for strong relation to the occurrence and progress of retinoblastoma. Previously, we have demonstrated that lncRNA colon cancer-associated transcript 1 (CCAT1) in two RB cell lines SO-RB50 and Y79 was obviously overexpressed, and notably, lncRNA CCAT1 attenuated miR-218-5p expressionand induced proliferation, cell migration and invasion. But, how lncRNA CCAT1 acts in RB development and the potential molecular mechanisms remain to be determined. In this study, the expression levels of lncRNA CCAT1 and miR-218-5p were evaluated in RB tissues by Q-PCR, which established the results in the cell lines. Further, lncRNA CCAT1 was shown to promote epithelial-to-mesenchymal transition (EMT), cellular migration and invasion of RB cells by functional analysis of downregulation and overexpression of lncRNA CCAT1 with specific siRNA and pcDNA transfection. By performing bioinformatics and dual luciferase reporter assay, we verified the direct interaction between lncRNA CCAT1 and miR-218-5p. Besides, bioinformatics analysis indicated that metal regulatory transcription factor 2 (MTF2) might be a potent novel target for miR-218-5p, which was further validated with luciferase reporter assay, Q-PCR and also Western blot analysis. Functional analysis and rescue analysis showed that lncRNA CCAT1 via competitive binding to miR-218-5p to modulate MTF2 expression thus accelerate EMT, cell migration and invasion of RB. In conclusion, here we identified the lncRNA CCAT1/miR-218-5p/MTF2 axis in RB cell lines. Our investigations on the function of lncRNA CCAT1 and the roles of the related molecules hint a novel potential target fo RB therapy.

Automated summary

The study identified the lncRNA CCAT1/miR-218-5p/MTF2 axis in RB cell lines, showing that lncRNA CCAT1 accelerates RB development by promoting EMT, cell migration, and invasion, and interacts directly with miR-218-5p and MTF2. This suggests a novel potential target for RB therapy.