RETRACTED: CircTLK1 promotes the proliferation and metastasis of renal cell carcinoma by sponging miR-136-5p

被引:123
作者
Li, Jianfa [1 ]
Huang, Chenchen [1 ,2 ]
Zou, Yifan [3 ]
Ye, Jing [1 ]
Yu, Jing [4 ]
Gui, Yaoting [1 ,2 ]
机构
[1] Peking Univ, Shenzhen Peking Univ Hong Kong Univ Sci & Technol, Guangdong & Shenzhen Key Lab Male Reprod Med & Gen, Shenzhen Hosp,Inst Urol, Shenzhen 518000, Peoples R China
[2] Anhui Med Univ, Hefei 230000, Anhui Province, Peoples R China
[3] Shenzhen Univ, Affliated Luohu Hosp, Dept Urol, Shenzhen 518000, Peoples R China
[4] Peking Univ, Shenzhen Hosp, Dept Lab Med, Shenzhen 518000, Peoples R China
基金
国家重点研发计划;
关键词
Renal cell carcinoma; circTLK1; miR-136-5p; CBX4; VEGFA; LONG NONCODING RNAS; CIRCULAR RNAS; HEPATOCELLULAR-CARCINOMA; SUMO MODIFICATION; CANCER CELLS; BIOGENESIS;
D O I
10.1186/s12943-020-01225-2
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
BackgroundCircular RNAs (circRNAs), a novel type of noncoding RNA (ncRNA), are covalently linked circular configurations that form via a loop structure. Accumulating evidence indicates that circRNAs are potential biomarkers and key regulators of tumor development and progression. However, the precise roles of circRNAs in renal cell carcinoma (RCC) remain unknown.MethodsThrough circRNA high-throughput sequencing of RCC cell lines, we identified the circRNA TLK1 (circTLK1) as a novel candidate circRNA derived from the TLK1 gene. qRT-PCR detected the mRNA, circRNA and miRNA expression levels in RCC tissues and cells. Loss-of function experiments were executed to detect the biological roles of circTLK1 in the RCC cell phenotypes in vitro and in vivo. RNA-FISH, RNA pull-down, dual-luciferase reporter, western blot and immunohistochemistry assays were used to investigate the molecular mechanisms underlying the functions of circTLK1.ResultscircTLK1 is overexpressed in RCC, and expression is positively correlated with distant metastasis and unfavorable prognosis. Silencing circTLK1 significantly inhibited RCC cell proliferation, migration and invasion in vitro and in vivo. circTLK1 was mainly distributed in the cytoplasm and positively regulated CBX4 expression by sponging miR-136-5p. Forced CBX4 expression reversed the circTLK1 suppression-induced phenotypic inhibition of RCC cells. Moreover, CBX4 expression was positively correlated with VEGFA expression in RCC tissues. CBX4 knockdown significantly inhibited VEGFA expression in RCC cells.ConclusionCollectively, our findings demonstrate that circTLK1 plays a critical role in RCC progression by sponging miR-136-5p to increase CBX4 expression. circTLK1 may act as a diagnostic biomarker and therapeutic target for RCC.
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页数:17
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