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

By Qiupeng Zheng, Chunyang Bao, Weijie Guo, Shuyi Li, Jie Chen, Bing Chen, Yanting Luo, Dongbin Lyu, Yan Li, Guohai Shi and 4 more. Nature Communications, 2016

1,844 citations recorded by the source corpus.

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. Circular RNAs are formed from exon back-splicing, the significance of these endogenous RNAs is beginning to be unraveled. Here, the authors identify thousands of circular RNAs differentially expressed between normal and cancer tissues and show that an abundant circular RNA generated from HIPK3regulates cell growth.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3628580c945dbfb3230ed1b5b36c7f70926f28e3

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Citations in the corpus

Noncoding RNA:RNA Regulatory Networks in Cancer (2018, methodology): “CircRNA profiling was used to identify circHIPK3 as a highly abundant circRNA in various cancers [146].”
Non-coding RNAs in disease: from mechanisms to therapeutics (2023, positive): “…. circRNAs can interact with miRNAs, mRNAs or RNA-binding proteins (RBPs), activate or repress gene expression, or act as miRNA or protein sponges 76 SWINGN lncRNA, which is transcribed from an enhancer, modulates the activation of GAS6 oncogene by binding to SWI/SNF tumour suppressor complex…”
Past, present, and future of circRNAs (2019, positive): “Other studies support this finding (Ashwal-Fluss et al , 2014; Zheng et al , 2016; Liang et al , 2017). circRNAs might have even longer half-life in vivo , particularly in cell types that do not divide.”
Circular RNA and its mechanisms in disease: From the bench to the clinic. (2018, background): “Through analyses of transcriptome sequencing datasets with computational pipelines that specifically search for back-splicing junctions, the expression of circRNAs has been widely detected in a large number ofmetazoans and in diverse cell types and organisms, ranging from fruit flies to humans (Ivan”
exoRBase: a database of circRNA, lncRNA and mRNA in human blood exosomes (2017, background): “We also integrated the tissue types of expressed circRNAs from the results of our previous research, where 27 296 circRNAs were detected from six tissues (11).”
CircRNA: a novel type of biomarker for cancer (2017, background): “Notably, it is found that circHIPK3 is significantly overexpressed in liver cancer than normal tissues [27].”
Circular RNA identification based on multiple seed matching (2018, background): “in cytoplasm [7, 8], nucleus-localized EIciRNAs were found to function as parental gene transcription activators [9].”
Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma. (2018, methodology): “To further confirm this result, according to the method as previously reported[16], we performed a luciferase assay using these two miRNAs.”
Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis (2017, background): “, 2013) and for circ-HIPK3 in human cancers (Zheng et al., 2016).”
Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1 (2017, methodology): “Cloning for CircPABPN1 overexpression was performed as described.(13,15) Briefly, genomic DNA was isolated using DNeasy Blood & Tissue Kit (69504, Qiagen) and 25 ng of genomic DNA was used to amplify »500-bp genomic sequences upstream and downstream of the PABPN1 (NM_004643.”
Novel Role of FBXW7 Circular RNA in Repressing Glioma Tumorigenesis (2017, background): “Among these multiple functions, “miRNA sponge” represents the most conspicuous function (12,13,39).”