Oncogenic Role of Fusion-circRNAs Derived from Cancer-Associated Chromosomal Translocations

被引：524

作者：

Guarnerio, Jlenia ^{[1
,2
]}

Bezzi, Marco ^{[1
,2
]}

Jeong, Jong Cheol ^{[2
]}

Paffenholz, Stella V. ^{[1
,2
]}

Berry, Kelsey ^{[1
,2
]}

Naldini, Matteo M. ^{[1
,2
]}

Lo-Coco, Francesco ^{[3
,4
]}

Tay, Yvonne ^{[5
,6
]}

Beck, Andrew H. ^{[2
]}

Pandolfi, Pier Paolo ^{[1
,2
]}

机构：

[1] Harvard Univ, Beth Israel Deaconess Med Ctr, Beth Israel Deaconess Canc Ctr, Canc Res Inst,Dept Med,Med Sch, Boston, MA 02215 USA

[2] Harvard Univ, Beth Israel Deaconess Med Ctr, Beth Israel Deaconess Canc Ctr, Canc Res Inst,Dept Pathol,Med Sch, Boston, MA 02215 USA

[3] Univ Roma Tor Vergata, Dept Biomed & Prevent, I-00173 Rome, Italy

[4] Fdn Santa Lucia, I-00173 Rome, Italy

[5] Natl Univ Singapore, Yong Loo Lin Sch Med, Canc Sci Inst Singapore, Singapore 117597, Singapore

[6] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117597, Singapore

来源：

CELL | 2016年 / 165卷 / 02期

关键词：

ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE MYELOID-LEUKEMIA; CIRCULAR RNAS; CELL-LINE; MICRORNA; TRANSCRIPTION; SEQUENCES; DIAGNOSIS; BIOMARKER; PROTEINS;

D O I：

10.1016/j.cell.2016.03.020

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：

Chromosomal translocations encode oncogenic fusion proteins that have been proven to be causally involved in tumorigenesis. Our understanding of whether such genomic alterations also affect non-coding RNAs is limited, and their impact on circular RNAs (circRNAs) has not been explored. Here, we show that well-established cancer-associated chromosomal translocations give rise to fusion circRNAs (f-circRNA) that are produced from transcribed exons of distinct genes affected by the translocations. F-circRNAs contribute to cellular transformation, promote cell viability and resistance upon therapy, and have tumor-promoting properties in in vivo models. Our work expands the current knowledge regarding molecular mechanisms involved in cancer onset and progression, with potential diagnostic and therapeutic implications.

引用

页码：289 / 302

页数：14

共 50 条

[1] Pediatric sarcomas: translating molecular pathogenesis of disease to novel therapeutic possibilities [J].