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Integrated analysis of circRNAs and mRNAs expression profile revealed the involvement of hsa_circ_0007919 in the pathogenesis of ulcerative colitis

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Abstract

Background

Ulcerative colitis (UC) is characterized by chronic inflammation in the colon and epigenetic factors underlying the occurrence. Circular RNAs (circRNAs) have been under intensive focus due to the circular construct and gene-regulating functions. However, the changes and roles of circRNAs in UC remain unknown.

Methods

Microarrays were used to detect the differentially expressed genes, and quantitative real-time PCR was used to identify the changes in UC. In silico analyses were performed to predict the functions of circRNAs and mRNAs. In vitro, epithelial cell lines were stimulated by pro-inflammation effectors to test the alterations in circRNAs. CircRNAs–microRNAs–mRNAs network clarified the potential mechanisms underlying circRNAs in UC. The binding site between hsa_circ_0007919 and miR-138 or let-7a was verified using dual-luciferase assay.

Results

A total of 264 significantly dysregulated circRNAs and 1869 differentially expressed mRNAs in inflamed mucosa were compared with the non-inflamed mucosa in UC. Hsa_circ_0004662 and hsa_circ_0007919 were altered largely in UC tissues. Hsa_circ_0007919 was reduced persistently after inflammatory treatments, and it was relevant to Mayo endoscopic subscores and the expression of tight junction molecules. Finally, hsa_circ_0007919 could harbor miR-138, and let-7a to regulate the targeted mRNAs EPC1 and VIPR1.

Conclusions

Several circRNAs were differentially expressed in UC. Hsa_circ_0007919 is related to clinical characteristics and epithelial integrity by binding to hsa-let-7a, hsa-miR-138 to regulate the target genes. CircRNAs, especially hsa_circ_0007919, are associated with the pathogenesis and development of UC, with potential diagnostic and therapeutic implications.

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Abbreviations

UC:

Ulcerative colitis

circRNAs:

Circular RNAs

GO:

Gene ontology

KEGG:

Kyoto Encyclopedia of Genes and Genome

BP:

Biological process

CC:

Cellular component

MF:

Molecular function

CRC:

Colorectal cancer

TNF-α:

Tumor necrosis factor-α

IL1-β:

Interleukin 1β

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Acknowledgements

This work was supported by the Peking University People’s Hospital Research and Development Funds Project (Grant No. RDX2018-05).

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Author notes

  1. Tingting Wang and Ning Chen share the co-first authorship.

Authors and Affiliations

  1. Institute of Clinical Molecular Biology and Central Laboratory, Peking University People’s Hospital, No.11 Xizhimen South Street, Beijing, 100044, People’s Republic of China

    Tingting Wang, Weixia Ren, Fangfang Gao, Lei Ye, Ying Han & Yujun Zhang

  2. Department of Gatroenterology, Peking University People’s Hospital, No. 11 Xizhimen South Street, Beijing, 100044, People’s Republic of China

    Tingting Wang, Ning Chen & Yulan Liu

  3. Department of Pathology, Peking University People’s Hospital, No.11 Xizhimen South Street, Beijing, 100044, People’s Republic of China

    Fangfang Liu

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  1. Tingting Wang
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Correspondence to Yujun Zhang or Yulan Liu.

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This study was approved by the Human Ethics Committee of the Peking University People’s Hospital and conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was acquired from all the participants in the study prior to the collection of samples. All the work that involved RNA and DNA in this study was conducted under institutional biosafety committee (IBC)-approved protocols approved at the Peking University People’s Hospital.

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Wang, T., Chen, N., Ren, W. et al. Integrated analysis of circRNAs and mRNAs expression profile revealed the involvement of hsa_circ_0007919 in the pathogenesis of ulcerative colitis. J Gastroenterol 54, 804–818 (2019). https://doi.org/10.1007/s00535-019-01585-7

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