Abstract
Long-chain non-coding RNA (LncRNA) has been found to play an important role in the regulation of the occurrence and progression of renal cell carcinoma (RCC). In this study, we demonstrated that LncRNA NEAT1 expression and m6A methylation level was decreased in RCC tissues. Further, the downregulated expression level of LncRNA NEAT1 was associated with poor prognosis for RCC patients. Then we used CRIPSR/dCas13b-METTL3 to methylate LncRNA NEAT1 in RCC cells. The results showed that the expression level of LncRNA NEAT1 was upregulated after methylated by dCas13b-METTL3 in RCC cells. And the proliferation and migration ability of RCC cells was decreased after methylated LncRNA NEAT1. Finally, we examined the effect of LncRNA NEAT1 hypermethylation on the transcriptome. We found differentially expressed genes in RCC cells were associated with “cGMP-PKG signaling pathway”, “Cell adhesion molecules” and “Pathways in cancer”. In conclusion, CRISPR/Cas13b-METTL3 targeting LncRNA NEAT1 m6A methylation activates LncRNA NEAT1 expression and provides a new target for treatment of RCC.
Highlights
Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system and is the second leading cause of death among urinary system tumors
We detected the mRNA level of long chain noncoding RNA (LncRNA) NEAT1 in 10 pairs of RCC tumors and normal tissues
We observed that RCC patients with low expression of LncRNA NEAT1 had a poor prognosis compared with patients with high expression of LncRNA NEAT1 (Figure 1B)
Summary
Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system and is the second leading cause of death among urinary system tumors. About 30% of patients have already developed metastasis when renal cancer is diagnosed. The rise of targeted drugs in the past decade has offered promise and improved survival benefits for patients with advanced kidney cancer, yet most of these patients develop resistance between 6 and 15 months (Schmitt and Chang, 2016). It is important to further explore the underlying mechanisms of RCC pathogenesis and metastasis, and to find effective and reliable biomarkers for renal cancer progression and therapeutic targets. Human genome sequencing found that more than 80% of the genes coding no proteins, these non-coding gene transcription of RNAs contain a kind of important long chain noncoding RNA (LncRNA), the non-coding RNA length of more than 200 nucleotides (Lin and Yang, 2018).
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