Long non-coding RNA ARHGAP5-AS1 inhibits migration of breast cancer cell via stabilizing SMAD7 protein

doi:10.1007/s10549-021-06286-5

	Long non-coding RNA ARHGAP5-AS1 inhibits migration of breast cancer cell via stabilizing SMAD7 protein
	Wang, Chen-Long 1,2; Li, Jing-Chi 1; Zhou, Ci-Xiang 1; Ma, Cheng-Ning 1; Wang, Di-Fei 1; Wo, Lu-Lu 1; He, Ming 1; Yin, Qianqian4 ; He, Jian-Rong 3; Zhao, Qian 1
	2021-10
发表期刊	BREAST CANCER RESEARCH AND TREATMENT (IF:3.0[JCR-2023],3.9[5-Year])
ISSN	0167-6806
EISSN	1573-7217
卷号	189 期号:3 页码:607-619
DOI	10.1007/s10549-021-06286-5
摘要	Purpose Tumor metastasis is the main cause of death from breast cancer patients and cell migration plays a critical role in cancer metastasis. Recent studies have shown long non-coding RNAs (lncRNAs) play an essential role in the initiation and progression of cancer. In the present study, the role of an LncRNA, Rho GTPase Activating Protein 5- Antisense 1 (ARHGAP5-AS1) in breast cancer was investigated. Methods RNA sequencing was performed to find out dysregulated LncRNAs in MDA-MB-231-LM2 cells. Transwell migration assays and F-actin staining were utilized to estimate cell migration ability. RNA pulldown assays and RNA immunoprecipitation were used to prove the interaction between ARHGAP5-AS1 and SMAD7. Western blot and immunofluorescence imaging were used to examine the protein levels. Dual luciferase reporter assays were performed to evaluate the activation of TGF-beta signaling. Results We analyzed the RNA-seq data of MDA-MB-231 and its highly metastatic derivative MDA-MB-231-LM2 cell lines (referred to as LM2) and identified a novel lncRNA (NR_027263) named as ARHGAP5-AS1, which expression was significantly downregulated in LM2 cells. Further functional investigation showed ARHGAP5-AS1 could inhibit cell migration via suppression of stress fibers in breast cancer cell lines. Afterwards, SMAD7 was further identified to interact with ARHGAP5-AS1 by its PY motif and thus its ubiquitination and degradation was blocked due to reduced interaction with E3 ligase SMURF1 and SMURF2. Moreover, ARHGAP5-AS1 could inhibit TGF-beta signaling pathway due to its inhibitory role on SMAD7. Conclusion ARHGAP5-AS1 inhibits breast cancer cell migration via stabilization of SMAD7 protein and could serve as a novel biomarker and a potential target for breast cancer in the future.
关键词	lncRNA ARHGAP5-AS1 Breast cancer Metastasis SMAD7
收录类别	SCIE
语种	英语
WOS研究方向	Oncology
WOS类目	Oncology
WOS记录号	WOS:000683257800001
出版者	SPRINGER
原始文献类型	Article; Early Access
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/127930
专题	免疫化学研究所_特聘教授组_抗体化学实验室
通讯作者	He, Jian-Rong; Zhao, Qian
作者单位	1.Shanghai Jiao Tong Univ, Key Lab Cell Differentiat & Apoptosis, Natl Minist Educ, Dept Pathophysiol,Sch Med SJTU SM, 280 Chong Qing South Rd, Shanghai 200025, Peoples R China; 2.Xuzhou Med Univ, Dept Pathol, Xuzhou 221004, Jiangsu, Peoples R China; 3.Shanghai Jiao Tong Univ, Shanghai Ruijin Hosp, Comprehens Breast Hlth Ctr, Sch Med SJTU SM, 197 Rui Jin Er Rd, Shanghai 200025, Peoples R China; 4.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Wang, Chen-Long,Li, Jing-Chi,Zhou, Ci-Xiang,et al. Long non-coding RNA ARHGAP5-AS1 inhibits migration of breast cancer cell via stabilizing SMAD7 protein[J]. BREAST CANCER RESEARCH AND TREATMENT,2021,189(3):607-619.
APA	Wang, Chen-Long.,Li, Jing-Chi.,Zhou, Ci-Xiang.,Ma, Cheng-Ning.,Wang, Di-Fei.,...&Zhao, Qian.(2021).Long non-coding RNA ARHGAP5-AS1 inhibits migration of breast cancer cell via stabilizing SMAD7 protein.BREAST CANCER RESEARCH AND TREATMENT,189(3),607-619.
MLA	Wang, Chen-Long,et al."Long non-coding RNA ARHGAP5-AS1 inhibits migration of breast cancer cell via stabilizing SMAD7 protein".BREAST CANCER RESEARCH AND TREATMENT 189.3(2021):607-619.