Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs

Qiupeng Zheng; Chunyang Bao; Weijie Guo; Shuyi Li; Jie Chen; Bing Chen; Yanting Luo; Dongbin Lyu; Yan Li; Guohai Shi; Linhui Liang; Jianren Gu; Xianghuo He; Shenglin Huang

doi:10.1038/ncomms11215

Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs

Nat Commun. 2016 Apr 6:7:11215. doi: 10.1038/ncomms11215.

Authors

Qiupeng Zheng^{1

2}, Chunyang Bao¹, Weijie Guo^{1

2}, Shuyi Li^{1

2}, Jie Chen¹, Bing Chen¹, Yanting Luo¹, Dongbin Lyu¹, Yan Li¹, Guohai Shi¹, Linhui Liang¹, Jianren Gu², Xianghuo He¹, Shenglin Huang¹

Affiliations

¹ Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
² State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

Abstract

Circular RNAs (circRNAs) represent a class of widespread and diverse endogenous RNAs that may regulate gene expression in eukaryotes. However, the regulation and function of human circRNAs remain largely unknown. Here we generate ribosomal-depleted RNA sequencing data from six normal tissues and seven cancers, and detect at least 27,000 circRNA candidates. Many of these circRNAs are differently expressed between the normal and cancerous tissues. We further characterize one abundant circRNA derived from Exon2 of the HIPK3 gene, termed circHIPK3. The silencing of circHIPK3 but not HIPK3 mRNA significantly inhibits human cell growth. Via a luciferase screening assay, circHIPK3 is observed to sponge to 9 miRNAs with 18 potential binding sites. Specifically, we show that circHIPK3 directly binds to miR-124 and inhibits miR-124 activity. Our results provide evidence that circular RNA produced from precursor mRNA may have a regulatory role in human cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
Cell Cycle / genetics*
Cell Line, Tumor
Cell Proliferation
Gene Expression Regulation
Genes, Reporter
HCT116 Cells
HeLa Cells
Hepatocytes / cytology
Hepatocytes / metabolism
Humans
Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
Intracellular Signaling Peptides and Proteins / genetics*
Intracellular Signaling Peptides and Proteins / metabolism
Luciferases / genetics
Luciferases / metabolism
MicroRNAs / genetics*
MicroRNAs / metabolism
Molecular Sequence Annotation
Molecular Sequence Data
Organ Specificity
Protein Serine-Threonine Kinases / antagonists & inhibitors
Protein Serine-Threonine Kinases / genetics*
Protein Serine-Threonine Kinases / metabolism
RNA / antagonists & inhibitors
RNA / genetics*
RNA / metabolism
RNA, Circular
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Sequence Analysis, RNA
Signal Transduction

Substances

Intracellular Signaling Peptides and Proteins
MIRN124 microRNA, human
MicroRNAs
RNA, Circular
RNA, Small Interfering
RNA
Luciferases
HIPK3 protein, human
Protein Serine-Threonine Kinases