Differential functions of RhoGDIβ in malignant transformation and progression of urothelial cell following N-butyl-N-(4-hydmoxybutyl) nitrosamine exposure

doi:10.1186/s12915-023-01683-2

科研成果详情

题名	Differential functions of RhoGDIβ in malignant transformation and progression of urothelial cell following N-butyl-N-(4-hydmoxybutyl) nitrosamine exposure
作者	Hua, Xiaohui 1,2; Zou, Ronghao 1; Bai, Xiaoyue 1; Yang, Yuyao 1; Lu, Juan 1; Huang, Chuanshu2
发表日期	2023-08-28
发表期刊	BMC biology 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Bladder carcinogenesis Cancer invasion RhoGDIβ Tumor promotion/progression
其他关键词	GDP-DISSOCIATION INHIBITOR ; BREAST-CANCER ; ISORHAPONTIGENIN ISO ; EXPRESSION ; BLADDER ; METASTASIS ; INVASION ; GENE ; BIOMARKER ; GTPASES
摘要	Functional role of Rho GDP-dissociation inhibitor beta (RhoGDIβ) in tumor biology appears to be contradictory across various studies. Thus, the exploration of the molecular mechanisms underlying the differential functions of this protein in urinary bladder carcinogenesis is highly significant in the field. Here, RhoGDIβ expression patterns, biological functions, and mechanisms leading to transformation and progression of human urothelial cells (UROtsa cells) were evaluated following varying lengths of exposure to the bladder carcinogen N-butyl-N-(4-hydmoxybutyl) nitrosamine (BBN)., It was seen that compared to expression in vehicle-treated control cells, RhoGDIβ protein expression was downregulated after 2-month of BBN exposure, but upregulated after 6-month of exposure. Assessments of cell function showed that RhoGDIβ inhibited UROtsa cell growth in cells with BBN for 2-month exposure, whereas it promoted the invasion of cells treated with BBN for 6 months. Mechanistic studies revealed that 2-month of BBN exposure markedly attenuated DNMT3a abundance, and this led to reduced miR-219a promoter methylation, increased miR-219a binding to the RhoGDIβ mRNA 3'UTR, and reduced RhoGDIβ protein translation. While after 6-mo of BBN treatment, the cells showed increased PP2A/JNK/C-Jun axis phosphorylation and this in turn mediated overall RhoGDIβ mRNA transcription and protein expression as well as invasion., These findings indicate that RhoGDIβ is likely to inhibit the transformation of human urothelial cells during the early phase of BBN exposure, whereas it promotes invasion of the transformed/progressed urothelial cells in the late stage of BBN exposure. The studies also suggest that RhoGDIβ may be a useful biomarker for evaluating the progression of human bladder cancers.
资助项目	Natural Science Foundation of China[NSFC81773391];Natural Science Foundation of China[NSFC81702530];Oujiang Research Project[OJQD2022006];Scientific Research Foundation of Education Department of Anhui Province of China[KJ2020A0154]
出版者	BMC
ISSN	1741-7007
EISSN	1741-7007
卷号	21 期号:1
DOI	10.1186/s12915-023-01683-2
页数	15
WOS类目	Biology
WOS研究方向	Life Sciences & Biomedicine - Other Topics
WOS记录号	WOS:001056355700001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	37635218
SCOPUSEID	2-s2.0-85169138606
通讯作者地址	[Huang, Chuanshu]Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine,Vision and Brain Health),Key Laboratory of Laboratory Medicine,Ministry of Education,School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
Scopus学科分类	Biotechnology;Structural Biology;Ecology, Evolution, Behavior and Systematics;Physiology;Biochemistry, Genetics and Molecular Biology (all);Agricultural and Biological Sciences (all);Plant Science;Developmental Biology;Cell Biology
TOP期刊	TOP期刊
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/182509
专题	检验医学院（生命科学学院、生物学实验教学中心）
通讯作者	Huang, Chuanshu
作者单位	1.Department of Occupational Health and Environmental Health,School of Public Health,Anhui Medical University,Anhui,Hefei,230032,China; 2.Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine,Vision and Brain Health),Key Laboratory of Laboratory Medicine,Ministry of Education,School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
第一作者单位	检验医学院（生命科学学院、生物学实验教学中心）
通讯作者单位	检验医学院（生命科学学院、生物学实验教学中心）
推荐引用方式 GB/T 7714	Hua, Xiaohui,Zou, Ronghao,Bai, Xiaoyue,et al. Differential functions of RhoGDIβ in malignant transformation and progression of urothelial cell following N-butyl-N-(4-hydmoxybutyl) nitrosamine exposure[J]. BMC biology,2023,21(1).
APA	Hua, Xiaohui, Zou, Ronghao, Bai, Xiaoyue, Yang, Yuyao, Lu, Juan, & Huang, Chuanshu. (2023). Differential functions of RhoGDIβ in malignant transformation and progression of urothelial cell following N-butyl-N-(4-hydmoxybutyl) nitrosamine exposure. BMC biology, 21(1).
MLA	Hua, Xiaohui,et al."Differential functions of RhoGDIβ in malignant transformation and progression of urothelial cell following N-butyl-N-(4-hydmoxybutyl) nitrosamine exposure".BMC biology 21.1(2023).