https://orcid.org/0000-0001-9556-8771
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Abstract
Aims: Few circRNAs have been thoroughly explored in ulcerative colitis (UC). Materials & methods: Microarrays and qualitative real-time PCRs were used to detect and confirm dysregulated circRNAs associated with UC. Functional analysis was performed to explore the roles. Results: A total of 580 circRNAs and 87 miRNAs were simultaneously dysregulated in both inflamed and noninflamed UC colonic mucosa compared with healthy controls. Accordingly, hsa_circ_0001021 was significantly downregulated in patients with UC and was related to Mayo scores. Clinical samples and cell experiments revealed that hsa_circ_0001021 was expressed in epithelial cells and correlated with ZO-1, occludin and CLDN-2. Moreover, hsa_circ_0001021 sponged miR-224-5p to upregulate smad4 and increased ZO-1 and occludin. Conclusion: Hsa_circ_0001021 is related to UC severity and regulates epithelial barrier function via sponging miR-224-5p.
Lay abstract
Ulcerative colitis (UC) is a long-term inflammatory disease affecting the gut. Understanding how UC affects the cells of the gut can help us better understand the disease. This study identified several types of RNA molecules, including circRNA, microRNAs and messenger RNAs, that were unbalanced in the colon tissue of patients with UC compared with healthy controls. A type of circRNA, called hsa_circ_0001021, regulates genes involved in healthy intestinal function. This circRNA was significantly downregulated in patients with UC and may be a potential target for future treatments.
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2021-0230
Author contributions
B Li and X Zuo conceived and designed the study. B Li, Y Li and L Li performed experiments. B Li and Y Yu performed statistical analysis. Y Li, L Li, Y Yu, X Gu, C Liu, X Long and Y Yu provided vital expertise and advice. B Li drafted the manuscript. All authors read the manuscript and approved the submitted version.
Acknowledgments
The authors thank Y-N Xia, L Lin, R Zhou and X-Y Li for their valuable support and advice during the research and manuscript drafting. The authors also thank the colleagues of Hangzhou Lianchuan Biotechnology Co. Ltd. for their assistance in RNA sequencing and analysis.
Financial & competing interests disclosure
This work was supported by the National Natural Science Foundation of China (no. 81770538, no. 82070551, no. 82070540 and no. 81900486), National Natural Science Foundation of China Key Research and Development Program of Shandong Province (2019GHZ022). The study is also supported by the Taishan Scholars Program of Shandong Province. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The study was conducted according to the guidelines of the Declaration of Helsinki, and human studies were approved by the ethics committees in Qilu Hospital of Shandong University (protocol code: KYLL-2017(KS)-509). In addition, for investigations involving human subjects, informed written consent has been obtained from the legal guardians of each participant.
Data sharing statement
The circRNAs and mRNAs microarray datasets presented in this study can be found in the National Center for Biotechnology Information (NCBI) database with accession code GSE178753. The miRNAs sequencing datasets presented in this study can be found in the NCBI database with accession code PRJNA739883.