Targeted Demethylation of the PLOD2 mRNA Inhibits the Proliferation and Migration of Renal Cell Carcinoma

被引:14
作者
Cao, Congcong [1 ]
Ma, Qian [1 ]
Huang, Xinbo [1 ]
Li, Aolin [2 ]
Liu, Jun [2 ]
Ye, Jing [1 ]
Gui, Yaoting [1 ]
机构
[1] Hong Kong Univ Sci & Technol, Shenzhen Peking Univ, Guangdong & Shenzhen Key Lab Male Reprod Med & Ge, Inst Urol,Peking Univ,Shenzhen Hosp,Med Ctr, Shenzhen, Peoples R China
[2] Peking Univ, Hosp 1, Dept Urol, Beijing, Peoples R China
基金
中国国家自然科学基金; 国家重点研发计划;
关键词
CRISPR; dCas13b; (N6-methyladenosine); PLOD2; renal cell cancer; NUCLEAR-RNA; N6-METHYLADENOSINE; METHYLATION; EXPRESSION;
D O I
10.3389/fmolb.2021.675683
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
N6-methyladenosine (m(6)A) RNA modification is the most common internal mRNA modification in mammals and has been reported to play a key role in gene expression regulation. In this study, we detected a high level of m(6)A methylation of the PLOD2 3 '-untranslated regions (3 ' UTR) in renal cell carcinoma (RCC). Furthermore, we found that the high expression level of PLOD2 was a prognostic indicator for patients with RCC. A dm(6)ACRISPR demethylation system was performed to accurately and specifically demethylate 3 ' UTR of PLOD2 and caused an inactivation of PLOD2 expression. Furthermore, we also performed many in vitro experiments to confirm that PLOD2 exerted tumor promoter effects by promoting tumor proliferation and migration. In conclusion, PLOD2 mRNA demethylated by dCas13b-ALKBH5 might provide a new light on the treatment for RCC.
引用
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页数:10
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