Profiling and functional analysis of circular RNAs in acute promyelocytic leukemia and their dynamic regulation during all-trans retinoic acid treatment

Cell Death & Disease
Shufen LiKankan Wang

Abstract

Circular RNAs (circRNAs) are a novel class of powerful regulators in gene expression and participate in the pathogenesis of many diseases, including cancer. However, little is known about the roles of circRNAs in the development and treatment of acute promyelocytic leukemia (APL). Here we report the expression profiling and function of circRNAs in APL, including their dynamic regulation during all-trans retinoic acid (ATRA)-induced differentiation. We performed two independent ribosomal RNA-minus RNA-sequencing (Ribo-minus RNA-seq) experiments with and without RNase R treatment on APL patient-derived NB4 cells and identified a total of 4313 circRNAs, including 1098 newly identified circRNAs. Detailed analysis showed that circRNAs expressed in APL cells were mostly exon-derived, not by-products during splicing, and could be distinguished from hematopoietic stem cells, neutrophils and lymphocytes. The true presence and stability of circRNAs were verified both in NB4 cells and primary APL patient samples. Moreover, we conducted a time-series analysis of circRNAs on ATRA-treated NB4 cells and uncovered 508 circRNAs with dynamic expression during ATRA treatment, including 246 upregulated and 262 downregulated. Further evidence demon...Continue Reading

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Methods Mentioned

BETA
RNA-seq
conducted
reverse transcription-PCR
PCR
quantitative reverse
CLIP-Seq
transfection
Assay

Software Mentioned

Cufflinks
GraphPad Prism6
STAR
AS
ENSEMBL
miRanda
Targetscan
FUCHS
R
CIRI

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