Abstract
Long non-coding RNAs (lncRNAs) play a critical role in cancer progression, including in nasopharyngeal carcinoma (NPC). However, it is still poorly understood whether lncRNA regulates epithelial to mesenchymal transition (EMT) and radioresistance of NPC cells. We found that lncRNA NEAT1 was significantly upregulated in NPC cell lines and tissues. Knockdown of NEAT1 could sensitize NPC cells to radiation in vitro. Further investigation found that NEAT1 regulated radioresistance by modulating EMT phenotype. Furthermore, we found that there was reciprocal repression between NEAT1 and miR-204. ZEB1 was identified as a downstream target of miR-204 and NEAT1 upregulated ZEB1 expression by negatively regulating miR-204 expression. Taking together, we proposed that NEAT1 regulated EMT phenotype and radioresistance by modulating the miR-204/ZEB1 axis in NPC.
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Yaoyong Lu, Tao Li, Ganbao Wei and Lianbo Liu contributed equally to this work.
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Supplementary Figure 1
Enforced expression of ZEB1 Restores the effects of NEAT1 down-regulation on radiosensitivity and EMT phenotype. (A) ZEB1 expression was verified by western blot. (B) and (C) Ectopic expression of ZEB1 significantly reduced NEAT1-knockdown-induced radiosensitivity, as indicated by clonogenic assay and cell apoptosis assay. (D) ZEB1 could restore the expression of Bcl-2 and active caspase-3,which was triggered by NEAT1 down-regulation. (E) ZEB1 overexpression counteracted the effect of NEAT1 down-regulation on EMT phenotype. (GIF 39 kb)
Supplementary Figure 2
The transcriptional interference effect by sh-NEAT1 or over-expression by pCDNA-NEAT1 was evaluated. (A) NEAT1 was knock-downed in 5-8F cells with the use of sh-RNA. (B) 5-8F cells were transfected with pcDNA-NEAT1 plasmid and the effect was evaluated by RT-PCT. (GIF 17 kb)
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(GIF 14 kb)
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Lu, Y., Li, T., Wei, G. et al. The long non-coding RNA NEAT1 regulates epithelial to mesenchymal transition and radioresistance in through miR-204/ZEB1 axis in nasopharyngeal carcinoma. Tumor Biol. 37, 11733–11741 (2016). https://doi.org/10.1007/s13277-015-4773-4
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DOI: https://doi.org/10.1007/s13277-015-4773-4