ciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma

Abstract Circular RNAs are a new class of non-coding RNAs that have been shown to play critical roles in the development and progression of renal cell carcinoma (RCC). However, little is known about the functional mechanisms and therapeutic role of ciRS-7 in RCC. A series of in vitro and in vivo exp...

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Autores principales:	Weipu Mao, Keyi Wang, Bin Xu, Hui Zhang, Si Sun, Qiang Hu, Lei Zhang, Chunhui Liu, Shuqiu Chen, Jianping Wu, Ming Chen, Wei Li, Bo Peng
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Renal cell carcinoma ciRS-7 PBAE/si-ciRS-7 nanocomplexes Metastasis Gene therapeutic Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/194304a09668424f9a42a2eb1771860f
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spelling	oai:doaj.org-article:194304a09668424f9a42a2eb1771860f2021-11-07T12:02:45ZciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma10.1186/s12943-021-01443-21476-4598https://doaj.org/article/194304a09668424f9a42a2eb1771860f2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12943-021-01443-2https://doaj.org/toc/1476-4598Abstract Circular RNAs are a new class of non-coding RNAs that have been shown to play critical roles in the development and progression of renal cell carcinoma (RCC). However, little is known about the functional mechanisms and therapeutic role of ciRS-7 in RCC. A series of in vitro and in vivo experiments were performed to investigate the functional mechanism and therapeutic role of ciRS-7, such as real-time quantitative PCR, CCK-8, wound healing, transwell, colony formation, Edu, tumor xenograft and lung metastasis in NSG mice. RNA pull-down, dual luciferase reporter, fluorescence in situ hybridization (FISH) and rescue assays were used to determine the relationship between ciRS-7, miR-139-3p and TAGLN. In addition, we constructed PBAE/si-ciRS-7 nanocomplexes with PBAE material to evaluate the therapeutic effect of the nanocomplexes on tumor in vivo. ciRS-7 was highly expressed in RCC tumor tissues and cell lines, and high ciRS-7 expression correlated with tumor size, high Fuhrman grade and poor survival. Depletion of ciRS-7 significantly inhibited RCC cell proliferation, invasion, tumor growth and metastasis in vivo, while overexpression of ciRS-7 had the opposite effect. Mechanistically, ciRS-7 acts as a "ceRNA" for miR-139-3p to prevent TAGLN degradation and promoting RCC progression and metastasis via the PI3K/AKT signaling pathway. In addition, miR-139-3p mimics or inhibitor could reverse the altered malignant tumor behavior caused by ciRS-7 overexpression or silencing. Furthermore, the PBAE/siciRS-7 nanocomplexes could significantly inhibit RCC tumor progression and metastasis in vivo. ciRS-7 acts as a tumor promoter by regulating the miR-139-3p/TAGLN axis and activating the PI3K/AKT signaling pathway to promote RCC progression and metastasis. Drug development of PBAE/si-ciRS-7 nanocomplexes targeting ciRS-7 may represent a promising gene therapeutic strategy for RCC.Weipu MaoKeyi WangBin XuHui ZhangSi SunQiang HuLei ZhangChunhui LiuShuqiu ChenJianping WuMing ChenWei LiBo PengBMCarticleRenal cell carcinomaciRS-7PBAE/si-ciRS-7 nanocomplexesMetastasisGene therapeuticNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Cancer, Vol 20, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Renal cell carcinoma ciRS-7 PBAE/si-ciRS-7 nanocomplexes Metastasis Gene therapeutic Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Renal cell carcinoma ciRS-7 PBAE/si-ciRS-7 nanocomplexes Metastasis Gene therapeutic Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Weipu Mao Keyi Wang Bin Xu Hui Zhang Si Sun Qiang Hu Lei Zhang Chunhui Liu Shuqiu Chen Jianping Wu Ming Chen Wei Li Bo Peng ciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma
description	Abstract Circular RNAs are a new class of non-coding RNAs that have been shown to play critical roles in the development and progression of renal cell carcinoma (RCC). However, little is known about the functional mechanisms and therapeutic role of ciRS-7 in RCC. A series of in vitro and in vivo experiments were performed to investigate the functional mechanism and therapeutic role of ciRS-7, such as real-time quantitative PCR, CCK-8, wound healing, transwell, colony formation, Edu, tumor xenograft and lung metastasis in NSG mice. RNA pull-down, dual luciferase reporter, fluorescence in situ hybridization (FISH) and rescue assays were used to determine the relationship between ciRS-7, miR-139-3p and TAGLN. In addition, we constructed PBAE/si-ciRS-7 nanocomplexes with PBAE material to evaluate the therapeutic effect of the nanocomplexes on tumor in vivo. ciRS-7 was highly expressed in RCC tumor tissues and cell lines, and high ciRS-7 expression correlated with tumor size, high Fuhrman grade and poor survival. Depletion of ciRS-7 significantly inhibited RCC cell proliferation, invasion, tumor growth and metastasis in vivo, while overexpression of ciRS-7 had the opposite effect. Mechanistically, ciRS-7 acts as a "ceRNA" for miR-139-3p to prevent TAGLN degradation and promoting RCC progression and metastasis via the PI3K/AKT signaling pathway. In addition, miR-139-3p mimics or inhibitor could reverse the altered malignant tumor behavior caused by ciRS-7 overexpression or silencing. Furthermore, the PBAE/siciRS-7 nanocomplexes could significantly inhibit RCC tumor progression and metastasis in vivo. ciRS-7 acts as a tumor promoter by regulating the miR-139-3p/TAGLN axis and activating the PI3K/AKT signaling pathway to promote RCC progression and metastasis. Drug development of PBAE/si-ciRS-7 nanocomplexes targeting ciRS-7 may represent a promising gene therapeutic strategy for RCC.
format	article
author	Weipu Mao Keyi Wang Bin Xu Hui Zhang Si Sun Qiang Hu Lei Zhang Chunhui Liu Shuqiu Chen Jianping Wu Ming Chen Wei Li Bo Peng
author_facet	Weipu Mao Keyi Wang Bin Xu Hui Zhang Si Sun Qiang Hu Lei Zhang Chunhui Liu Shuqiu Chen Jianping Wu Ming Chen Wei Li Bo Peng
author_sort	Weipu Mao
title	ciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma
title_short	ciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma
title_full	ciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma
title_fullStr	ciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma
title_full_unstemmed	ciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma
title_sort	cirs-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma
publisher	BMC
publishDate	2021
url	https://doaj.org/article/194304a09668424f9a42a2eb1771860f
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ciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma

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