Hsa_circRNA_103124 Upregulation in Crohn’s Disease Promotes Cell Proliferation and Inhibits Autophagy by Regulating the Hsa-miR-650/AKT2 Signaling Pathway

Circular RNAs (circRNAs) play important roles in the pathogenesis of Crohn’s disease (CD). We discovered that hsa_circRNA_103124 was upregulated in CD patients in our previous study. Nonetheless, the function of hsa_circRNA_103124 is unclear. In this study, hsa_circRNA_103124 was predicted to intera...

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Autores principales:	Juan Yin, Fuyi Tong, Yulan Ye, Tong Hu, Lijuan Xu, Liping Zhang, Jianyun Zhu, Zhi Pang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	hsa_circRNA_103124 hsa-miR-650 autophagy Cohn’s disease AKT2 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/d1246e79d12841eab746d817a4af4ebd
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spelling	oai:doaj.org-article:d1246e79d12841eab746d817a4af4ebd2021-11-05T14:28:04ZHsa_circRNA_103124 Upregulation in Crohn’s Disease Promotes Cell Proliferation and Inhibits Autophagy by Regulating the Hsa-miR-650/AKT2 Signaling Pathway1664-802110.3389/fgene.2021.753161https://doaj.org/article/d1246e79d12841eab746d817a4af4ebd2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.753161/fullhttps://doaj.org/toc/1664-8021Circular RNAs (circRNAs) play important roles in the pathogenesis of Crohn’s disease (CD). We discovered that hsa_circRNA_103124 was upregulated in CD patients in our previous study. Nonetheless, the function of hsa_circRNA_103124 is unclear. In this study, hsa_circRNA_103124 was predicted to interact with hsa-miR-650. Gene Ontology (GO) and pathway analyses identified AKT serine/threonine kinase 2 (AKT2) as the downstream target protein of hsa-miR-650. Activated AKT2 inhibits autophagy, but promotes cell proliferation. Recent studies suggest that the inhibition of autophagy is one of the mechanisms of CD pathogenesis. Therefore, we inferred that hsa_circRNA_103124 might regulate autophagy and proliferation by targeting AKT2 as a sponge for hsa-miR-650. Here, quantitative reverse transcription PCR (RT-QPCR) results revealed that upregulated hsa_circRNA_103124 expression in patients with CD was negatively correlated with hsa-miR-650 expression but positively correlated with the white blood cell count and calprotectin levels. TSC complex subunit 1 (TSC1), one of the proteins upstream of autophagy was downregulated in patients with CD. Consisting with the bioinformatics prediction, it was verified that hsa_circRNA_103124 targeted to hsa-miR650 by fluorescence in situ hybridization (FISH) and luciferase reporter assays. A hsa-miR-650 inhibitor reversed the promotion of rapamycin-induced autophagy and the inhibition of cell proliferation by the hsa_circRNA_103124 siRNA. However, hsa-miR-650 mimics reversed the inhibition of rapamycin-induced autophagy and the promotion of cell proliferation through hsa_circRNA_103124 overexpression. These results indicate that hsa_circRNA_103124 upregulation in patients with CD promotes cell proliferation and inhibits autophagy by regulating the hsa-miR-650/AKT2 signaling pathway.Juan YinFuyi TongYulan YeTong HuLijuan XuLiping ZhangJianyun ZhuZhi PangZhi PangFrontiers Media S.A.articlehsa_circRNA_103124hsa-miR-650autophagyCohn’s diseaseAKT2GeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hsa_circRNA_103124 hsa-miR-650 autophagy Cohn’s disease AKT2 Genetics QH426-470
spellingShingle	hsa_circRNA_103124 hsa-miR-650 autophagy Cohn’s disease AKT2 Genetics QH426-470 Juan Yin Fuyi Tong Yulan Ye Tong Hu Lijuan Xu Liping Zhang Jianyun Zhu Zhi Pang Zhi Pang Hsa_circRNA_103124 Upregulation in Crohn’s Disease Promotes Cell Proliferation and Inhibits Autophagy by Regulating the Hsa-miR-650/AKT2 Signaling Pathway
description	Circular RNAs (circRNAs) play important roles in the pathogenesis of Crohn’s disease (CD). We discovered that hsa_circRNA_103124 was upregulated in CD patients in our previous study. Nonetheless, the function of hsa_circRNA_103124 is unclear. In this study, hsa_circRNA_103124 was predicted to interact with hsa-miR-650. Gene Ontology (GO) and pathway analyses identified AKT serine/threonine kinase 2 (AKT2) as the downstream target protein of hsa-miR-650. Activated AKT2 inhibits autophagy, but promotes cell proliferation. Recent studies suggest that the inhibition of autophagy is one of the mechanisms of CD pathogenesis. Therefore, we inferred that hsa_circRNA_103124 might regulate autophagy and proliferation by targeting AKT2 as a sponge for hsa-miR-650. Here, quantitative reverse transcription PCR (RT-QPCR) results revealed that upregulated hsa_circRNA_103124 expression in patients with CD was negatively correlated with hsa-miR-650 expression but positively correlated with the white blood cell count and calprotectin levels. TSC complex subunit 1 (TSC1), one of the proteins upstream of autophagy was downregulated in patients with CD. Consisting with the bioinformatics prediction, it was verified that hsa_circRNA_103124 targeted to hsa-miR650 by fluorescence in situ hybridization (FISH) and luciferase reporter assays. A hsa-miR-650 inhibitor reversed the promotion of rapamycin-induced autophagy and the inhibition of cell proliferation by the hsa_circRNA_103124 siRNA. However, hsa-miR-650 mimics reversed the inhibition of rapamycin-induced autophagy and the promotion of cell proliferation through hsa_circRNA_103124 overexpression. These results indicate that hsa_circRNA_103124 upregulation in patients with CD promotes cell proliferation and inhibits autophagy by regulating the hsa-miR-650/AKT2 signaling pathway.
format	article
author	Juan Yin Fuyi Tong Yulan Ye Tong Hu Lijuan Xu Liping Zhang Jianyun Zhu Zhi Pang Zhi Pang
author_facet	Juan Yin Fuyi Tong Yulan Ye Tong Hu Lijuan Xu Liping Zhang Jianyun Zhu Zhi Pang Zhi Pang
author_sort	Juan Yin
title	Hsa_circRNA_103124 Upregulation in Crohn’s Disease Promotes Cell Proliferation and Inhibits Autophagy by Regulating the Hsa-miR-650/AKT2 Signaling Pathway
title_short	Hsa_circRNA_103124 Upregulation in Crohn’s Disease Promotes Cell Proliferation and Inhibits Autophagy by Regulating the Hsa-miR-650/AKT2 Signaling Pathway
title_full	Hsa_circRNA_103124 Upregulation in Crohn’s Disease Promotes Cell Proliferation and Inhibits Autophagy by Regulating the Hsa-miR-650/AKT2 Signaling Pathway
title_fullStr	Hsa_circRNA_103124 Upregulation in Crohn’s Disease Promotes Cell Proliferation and Inhibits Autophagy by Regulating the Hsa-miR-650/AKT2 Signaling Pathway
title_full_unstemmed	Hsa_circRNA_103124 Upregulation in Crohn’s Disease Promotes Cell Proliferation and Inhibits Autophagy by Regulating the Hsa-miR-650/AKT2 Signaling Pathway
title_sort	hsa_circrna_103124 upregulation in crohn’s disease promotes cell proliferation and inhibits autophagy by regulating the hsa-mir-650/akt2 signaling pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/d1246e79d12841eab746d817a4af4ebd
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Hsa_circRNA_103124 Upregulation in Crohn’s Disease Promotes Cell Proliferation and Inhibits Autophagy by Regulating the Hsa-miR-650/AKT2 Signaling Pathway

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