Large-scale circular RNA deregulation in T-ALL: unlocking unique ectopic expression of molecular subtypes

被引:39
作者
Buratin, Alessia [1 ,2 ]
Paganin, Maddalena [2 ,3 ]
Gaffo, Enrico [2 ]
Dal Molin, Anna [2 ]
Roels, Juliette [4 ,5 ,6 ]
Germano, Giuseppe [3 ,7 ]
Siddi, Maria Teresa [2 ]
Serafin, Valentina [3 ,7 ]
De Decker, Matthias [6 ]
Gachet, Stephanie [8 ,9 ,10 ]
Durinck, Kaat [4 ,5 ]
Speleman, Frank [4 ,5 ]
Taghon, Tom [5 ,6 ]
te Kronnie, Geertruij [7 ]
Van Vlierberghe, Pieter [4 ,5 ]
Bortoluzzi, Stefania [2 ,11 ]
机构
[1] Univ Padua, Dept Biol, Padua, Italy
[2] Univ Padua, Dept Mol Med, Via G Colombo 3, I-35131 Padua, Italy
[3] Fdn Citta Speranza Ist Ric Pediat, Padua, Italy
[4] Univ Ghent, Dept Biomol Med, Ghent, Belgium
[5] Canc Res Inst Ghent CRIG, Ghent, Belgium
[6] Univ Ghent, Dept Diagnost Sci, Ghent, Belgium
[7] Univ Padua, Maternal & Child Hlth Dept, Padua, Italy
[8] Hop St Louis, INSERM U944, Paris, France
[9] Hop St Louis, UMR7212, CNRS, Paris, France
[10] Univ Paris Diderot, St Louis Res Inst IRSL, Sorbonne Paris Cite, Paris, France
[11] Univ Padua, Interdept Res Ctr Innovat Biotechnol CRIBI, Padua, Italy
基金
欧洲研究理事会;
关键词
SIGNALING PATHWAY; CELL; GENE; LEUKEMIA; PROGRESSION; ACTIVATION; CANCER; TRANSLATION; COMPLEXES; REVEALS;
D O I
10.1182/bloodadvances.2020002337
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Circular RNAs (circRNAs) are stable RNA molecules that can drive cancer through interactions with microRNAs and proteins and by the expression of circRNA encoded peptides. The aim of the study was to define the circRNA landscape and potential impact in T-cell acute lymphoblastic leukemia (T-ALL). Analysis by CirComPara of RNA-sequencing data from 25 T-ALL patients, immature, HOXA overexpressing, TLX1, TLX3, TAL1, or LMO2 rearranged, and from thymocyte populations of human healthy donors disclosed 68 554 circRNAs. Study of the top 3447 highly expressed circRNAs identified 944 circRNAs with significant differential expression between malignant T cells and normal counterparts, with most circRNAs displaying increased expression in T-ALL. Next, we defined subtype-specific circRNA signatures in molecular genetic subgroups of human T-ALL. In particular, circZNF609, circPSEN1, circKPNA5, and circCEP70 were upregulated in immature, circTASP1, circZBTB44, and circBACH1 in TLX3, circHACD1, and circSTAM in HOXA, circCAMSAP1 in TLX1, and circCASC15 in TAL-LMO. Backsplice sequences of 14 circRNAs ectopically expressed in T-ALL were confirmed, and overexpression of circRNAs in T-ALL with specific oncogenic lesions was substantiated by quantification in a panel of 13 human cell lines. An oncogenic role of circZNF609 in T-ALL was indicated by decreased cell viability upon silencing in vitro. Furthermore, functional predictions identified circRNA-microRNA gene axes informing modes of circRNA impact in molecular subtypes of human T-ALL.
引用
收藏
页码:5902 / 5914
页数:13
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