Cargando…
Hsa_circRNA_102610 upregulation in Crohn’s disease promotes transforming growth factor-β1-induced epithelial-mesenchymal transition via sponging of hsa-miR-130a-3p
BACKGROUND: The incidence of inflammatory bowel disease, a chronic intestinal inflammatory disorder that includes Crohn’s disease (CD) and ulcerative colitis, is rising. Circular RNAs are considered valuable diagnostic biomarkers for CD. Current evidence supports the views that epithelial-mesenchyma...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304108/ https://www.ncbi.nlm.nih.gov/pubmed/32587447 http://dx.doi.org/10.3748/wjg.v26.i22.3034 |
_version_ | 1783548199547437056 |
---|---|
author | Yin, Juan Ye, Yu-Lan Hu, Tong Xu, Li-Juan Zhang, Li-Ping Ji, Ru-Ning Li, Ping Chen, Qian Zhu, Jian-Yun Pang, Zhi |
author_facet | Yin, Juan Ye, Yu-Lan Hu, Tong Xu, Li-Juan Zhang, Li-Ping Ji, Ru-Ning Li, Ping Chen, Qian Zhu, Jian-Yun Pang, Zhi |
author_sort | Yin, Juan |
collection | PubMed |
description | BACKGROUND: The incidence of inflammatory bowel disease, a chronic intestinal inflammatory disorder that includes Crohn’s disease (CD) and ulcerative colitis, is rising. Circular RNAs are considered valuable diagnostic biomarkers for CD. Current evidence supports the views that epithelial-mesenchymal transition (EMT) plays an important role in CD pathogenesis, and that hsa-miR-130a-3p can inhibit transforming growth factor-β1 (TGF-β1)-induced EMT. Our previous study revealed that hsa_circRNA_102610 was upregulated in CD patients. Moreover, we predicted an interaction between hsa_circRNA_102610 and hsa-miR-130a-3p. Thus, we hypothesized that hsa_circRNA_102610 may play roles in the proliferation and EMT of intestinal epithelial cells by sponging hsa-miR-130a-3p to participate in the pathogenesis of CD. AIM: To explore the mechanism of hsa_circRNA_102610 in the pathogenesis of CD. METHODS: The relative expression levels of hsa_circRNA_102610 and hsa-miR-130a-3p in patients were detected by quantitative reverse transcription-polymerase chain reaction. The proliferation of human intestinal epithelial cells (HIECs) and normal-derived colon mucosa cell line 460 (NCM460) cells was detected by cell counting kit-8, 5-ethynyl-2’-deoxyuridine staining and cell cycle assays following overexpression or downregulation of hsa_circRNA_102610. Cell proliferation assays were performed as described above in a rescue experiment with hsa-miR-130a-3p mimics. The interaction of hsa_circRNA_102610 and hsa-miR-130a-3p was verified by fluorescence in situ hybridization and dual luciferase reporter assays. The relative expression levels of CyclinD1, mothers against decapentaplegic homolog 4 (SMAD4), E-cadherin, N-cadherin and Vimentin were detected by western blotting following hsa_circRNA_102610 overexpression, TGF-β1-induced EMT or hsa-miR-130a-3p mimic transfection (in rescue experiments). RESULTS: Upregulation of hsa_circRNA_102610 was determined to be positively correlated with elevated fecal calprotectin levels in CD (r = 0.359, P = 0.007) by Pearson correlation analysis. Hsa_circRNA_102610 promoted the proliferation of HIECs and NCM460 cells, while hsa-miR-130a-3p reversed the cell proliferation-promoting effects of hsa_circRNA_102610. Fluorescence in situ hybridization and dual luciferase reporter assays showed that hsa_circRNA_102610 directly bound hsa-miR-130a-3p in NCM460 and 293T cells. An inverse correlation between downregulation of hsa-miR-130a-3p and upregulation of hsa_circRNA_102610 in CD patients was observed (r = -0.290, P = 0.024) by Pearson correlation analysis. Moreover, overexpression of hsa_circRNA_102610 promoted SMAD4 and CyclinD1 protein expression validated by western-blotting. Furthermore, over-expression of hsa_circRNA_102610 promoted TGF-β1 induced EMT in HIECs and NCM460 cells via targeting of hsa-miR-130a-3p, with increased expression of Vimentin and N-cadherin and decreased expression of E-cadherin. CONCLUSION: Hsa_circRNA_102610 upregulation in CD patients could promote the proliferation and EMT of intestinal epithelial cells via sponging of hsa-miR-130a-3p. |
format | Online Article Text |
id | pubmed-7304108 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-73041082020-06-24 Hsa_circRNA_102610 upregulation in Crohn’s disease promotes transforming growth factor-β1-induced epithelial-mesenchymal transition via sponging of hsa-miR-130a-3p Yin, Juan Ye, Yu-Lan Hu, Tong Xu, Li-Juan Zhang, Li-Ping Ji, Ru-Ning Li, Ping Chen, Qian Zhu, Jian-Yun Pang, Zhi World J Gastroenterol Basic Study BACKGROUND: The incidence of inflammatory bowel disease, a chronic intestinal inflammatory disorder that includes Crohn’s disease (CD) and ulcerative colitis, is rising. Circular RNAs are considered valuable diagnostic biomarkers for CD. Current evidence supports the views that epithelial-mesenchymal transition (EMT) plays an important role in CD pathogenesis, and that hsa-miR-130a-3p can inhibit transforming growth factor-β1 (TGF-β1)-induced EMT. Our previous study revealed that hsa_circRNA_102610 was upregulated in CD patients. Moreover, we predicted an interaction between hsa_circRNA_102610 and hsa-miR-130a-3p. Thus, we hypothesized that hsa_circRNA_102610 may play roles in the proliferation and EMT of intestinal epithelial cells by sponging hsa-miR-130a-3p to participate in the pathogenesis of CD. AIM: To explore the mechanism of hsa_circRNA_102610 in the pathogenesis of CD. METHODS: The relative expression levels of hsa_circRNA_102610 and hsa-miR-130a-3p in patients were detected by quantitative reverse transcription-polymerase chain reaction. The proliferation of human intestinal epithelial cells (HIECs) and normal-derived colon mucosa cell line 460 (NCM460) cells was detected by cell counting kit-8, 5-ethynyl-2’-deoxyuridine staining and cell cycle assays following overexpression or downregulation of hsa_circRNA_102610. Cell proliferation assays were performed as described above in a rescue experiment with hsa-miR-130a-3p mimics. The interaction of hsa_circRNA_102610 and hsa-miR-130a-3p was verified by fluorescence in situ hybridization and dual luciferase reporter assays. The relative expression levels of CyclinD1, mothers against decapentaplegic homolog 4 (SMAD4), E-cadherin, N-cadherin and Vimentin were detected by western blotting following hsa_circRNA_102610 overexpression, TGF-β1-induced EMT or hsa-miR-130a-3p mimic transfection (in rescue experiments). RESULTS: Upregulation of hsa_circRNA_102610 was determined to be positively correlated with elevated fecal calprotectin levels in CD (r = 0.359, P = 0.007) by Pearson correlation analysis. Hsa_circRNA_102610 promoted the proliferation of HIECs and NCM460 cells, while hsa-miR-130a-3p reversed the cell proliferation-promoting effects of hsa_circRNA_102610. Fluorescence in situ hybridization and dual luciferase reporter assays showed that hsa_circRNA_102610 directly bound hsa-miR-130a-3p in NCM460 and 293T cells. An inverse correlation between downregulation of hsa-miR-130a-3p and upregulation of hsa_circRNA_102610 in CD patients was observed (r = -0.290, P = 0.024) by Pearson correlation analysis. Moreover, overexpression of hsa_circRNA_102610 promoted SMAD4 and CyclinD1 protein expression validated by western-blotting. Furthermore, over-expression of hsa_circRNA_102610 promoted TGF-β1 induced EMT in HIECs and NCM460 cells via targeting of hsa-miR-130a-3p, with increased expression of Vimentin and N-cadherin and decreased expression of E-cadherin. CONCLUSION: Hsa_circRNA_102610 upregulation in CD patients could promote the proliferation and EMT of intestinal epithelial cells via sponging of hsa-miR-130a-3p. Baishideng Publishing Group Inc 2020-06-14 2020-06-14 /pmc/articles/PMC7304108/ /pubmed/32587447 http://dx.doi.org/10.3748/wjg.v26.i22.3034 Text en ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
spellingShingle | Basic Study Yin, Juan Ye, Yu-Lan Hu, Tong Xu, Li-Juan Zhang, Li-Ping Ji, Ru-Ning Li, Ping Chen, Qian Zhu, Jian-Yun Pang, Zhi Hsa_circRNA_102610 upregulation in Crohn’s disease promotes transforming growth factor-β1-induced epithelial-mesenchymal transition via sponging of hsa-miR-130a-3p |
title | Hsa_circRNA_102610 upregulation in Crohn’s disease promotes transforming growth factor-β1-induced epithelial-mesenchymal transition via sponging of hsa-miR-130a-3p |
title_full | Hsa_circRNA_102610 upregulation in Crohn’s disease promotes transforming growth factor-β1-induced epithelial-mesenchymal transition via sponging of hsa-miR-130a-3p |
title_fullStr | Hsa_circRNA_102610 upregulation in Crohn’s disease promotes transforming growth factor-β1-induced epithelial-mesenchymal transition via sponging of hsa-miR-130a-3p |
title_full_unstemmed | Hsa_circRNA_102610 upregulation in Crohn’s disease promotes transforming growth factor-β1-induced epithelial-mesenchymal transition via sponging of hsa-miR-130a-3p |
title_short | Hsa_circRNA_102610 upregulation in Crohn’s disease promotes transforming growth factor-β1-induced epithelial-mesenchymal transition via sponging of hsa-miR-130a-3p |
title_sort | hsa_circrna_102610 upregulation in crohn’s disease promotes transforming growth factor-β1-induced epithelial-mesenchymal transition via sponging of hsa-mir-130a-3p |
topic | Basic Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304108/ https://www.ncbi.nlm.nih.gov/pubmed/32587447 http://dx.doi.org/10.3748/wjg.v26.i22.3034 |
work_keys_str_mv | AT yinjuan hsacircrna102610upregulationincrohnsdiseasepromotestransforminggrowthfactorb1inducedepithelialmesenchymaltransitionviaspongingofhsamir130a3p AT yeyulan hsacircrna102610upregulationincrohnsdiseasepromotestransforminggrowthfactorb1inducedepithelialmesenchymaltransitionviaspongingofhsamir130a3p AT hutong hsacircrna102610upregulationincrohnsdiseasepromotestransforminggrowthfactorb1inducedepithelialmesenchymaltransitionviaspongingofhsamir130a3p AT xulijuan hsacircrna102610upregulationincrohnsdiseasepromotestransforminggrowthfactorb1inducedepithelialmesenchymaltransitionviaspongingofhsamir130a3p AT zhangliping hsacircrna102610upregulationincrohnsdiseasepromotestransforminggrowthfactorb1inducedepithelialmesenchymaltransitionviaspongingofhsamir130a3p AT jiruning hsacircrna102610upregulationincrohnsdiseasepromotestransforminggrowthfactorb1inducedepithelialmesenchymaltransitionviaspongingofhsamir130a3p AT liping hsacircrna102610upregulationincrohnsdiseasepromotestransforminggrowthfactorb1inducedepithelialmesenchymaltransitionviaspongingofhsamir130a3p AT chenqian hsacircrna102610upregulationincrohnsdiseasepromotestransforminggrowthfactorb1inducedepithelialmesenchymaltransitionviaspongingofhsamir130a3p AT zhujianyun hsacircrna102610upregulationincrohnsdiseasepromotestransforminggrowthfactorb1inducedepithelialmesenchymaltransitionviaspongingofhsamir130a3p AT pangzhi hsacircrna102610upregulationincrohnsdiseasepromotestransforminggrowthfactorb1inducedepithelialmesenchymaltransitionviaspongingofhsamir130a3p |