SUFU mediates EMT and Wnt/beta-catenin signaling pathway activation promoted by miRNA-324-5p in human gastric cancer

doi:10.1080/15384101.2020.1826632

	SUFU mediates EMT and Wnt/beta-catenin signaling pathway activation promoted by miRNA-324-5p in human gastric cancer
	Peng, Yin 1; Zhang, Xiaojing 1,2; Lin, Huijuan 3,4; Deng, Shiqi 1; Qin, Ying 5; Yuan, Yuan 1; Feng, Xianling 1; Wang, Jian 3; Chen, Wangchun 1; Hu, Fan 1; Yan, Ruibin 6; Zhao, Yanqiu 6; Cheng, Yulan 7,8; Wei, Yanjie 9; Fan, Xinmin 1; Ashktorab, Hassan 10,11; Smoot, Duane 12; Li, Song 6; Meltzer, Stephen J.7,8; Jin, Zhe 1
	2020-10-04
发表期刊	CELL CYCLE
ISSN	1538-4101
页码	14
摘要	The poor prognosis of late gastric carcinomas (GC) underscores the necessity to identify novel biomarkers for earlier diagnosis and effective therapeutic targets. MiRNA-324-5p has been shown to be over-expressed in GC, however the biological function of miRNA-324-5p implicated in gastric cancer and its downstream targets were not well understood. Wnt/beta-catenin signaling pathway is aberrantly regulated in GC. We sought to explore if miRNA-324-5p promotes oncogenesis through modulating Wnt signaling and EMT. MiRNA-324-5p is highly expressed in GC based on qRT-PCR and TCGA data. In addition, in vitro cell proliferation, cell migration assays and in vivo animal exenograft were executed to show that miRNA-324-5p is an oncogenic miRNA in GC. MiRNA-324-5p activates Wnt signaling and induces EMT in GC. Further, SUFU was identified as a target of miRNA-324-5p confirmed by western blotting and luciferase assays. Spearson analysis and TCGA data indicate that the expression of SUFU is negatively associated with the expression of miRNA-324-5p. Rescue experiments were performed to determine if SUFU mediates the Wnt activation, EMT and oncogenic function of miRNA-324-5p. MiRNA-324-5p inhibitors plus SUFU siRNAs rescue partially the inhibitory effect on Wnt signaling and EMT caused by miRNA-324-5p inhibitors. Finally, the suppression of cell proliferation, migration, and colony formation ability induced by miRNA-324-5p inhibitors is alleviated by addition of SUFU siRNAs. In summary, miRNA-324-5p is overexpressedin vivoand exerts cell growth and migration-promoting effects through activating Wnt signaling and EMT by targeting SUFU in GC. It represents a potential miRNA with an oncogenic role in human gastric cancer.
关键词	miRNA-324-5p SUFU negative regulator of hedgehog signaling Wnt/beta-catenin EMT
DOI	10.1080/15384101.2020.1826632
收录类别	SCI
语种	英语
资助项目	National Natural Youth Science Foundation of China[31601028] ; National Nature Science Foundation of China[81772592] ; National Science Foundation of China[81871969] ; Shenzhen Basic Research Fund[JCYJ20170818142852491] ; Shenzhen Basic Research Fund[JCYJ20160331190123578] ; Shenzhen Basic Research Fund[JCYJ20170413093358429] ; Shenzhen Basic Research Fund[JCYJ20190808163801777] ; Nature Science Foundation of Guangdong Province[2017A030313144] ; Nature Science Foundation of Guangdong Province[2017A030313479] ; Medical science and technology research foundation of Guangdong Province[A2019211] ; Medical science and technology research foundation of Guangdong Province[A2016112] ; Medical science and technology research foundation of Guangdong Province[A2018170] ; Shenzhen University[2018015] ; National Key Research and Development Program of China[2016YFB0201305] ; Science and Technology Program of Guangdong Province[2017B030301016] ; High Quality University Construction 2nd phase[860-00000210]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000575233200001
出版者	TAYLOR & FRANCIS INC
引用统计	被引频次：16[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/15631
专题	中国科学院计算技术研究所期刊论文_英文
通讯作者	Peng, Yin; Jin, Zhe
作者单位	1.Shenzhen Univ, Sch Med, Guangdong Key Lab Genome Stabil & Dis Prevent, Guangdong Prov Key Lab Reg Immun & Dis,Dept Patho, Shenzhen, Guangdong, Peoples R China 2.Guangdong Prov Key Lab Mol Oncol Pathol, Dept Pathol, Guangzhou, Guangdong, Peoples R China 3.Guangzhou Med Univ, Dept Pathol & Pathophysiol, Guangzhou, Guangdong, Peoples R China 4.Guangdong Women & Children Hosp, Dept Ultrasound, Guangzhou, Guangdong, Peoples R China 5.Shenzhen Second Peoples Hosp, Dept Gastrointestinal Surg, Shenzhen, Guangdong, Peoples R China 6.Peking Univ, Lab Chem Genom, Shenzhen Grad Sch, Shenzhen, Guangdong, Peoples R China 7.Johns Hopkins Univ, Sch Med, Dept Med, GI Div, Baltimore, MD 21205 USA 8.Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA 9.Shenzhen Inst Adv Technol, Ctr High Performance Comp, Shenzhen, Guangdong, Peoples R China 10.Howard Univ, Coll Med, Dept Med, Washington, DC USA 11.Howard Univ, Ctr Canc, Coll Med, Washington, DC 20059 USA 12.Meharry Med Ctr, Dept Med, Nashville, TN USA
推荐引用方式 GB/T 7714	Peng, Yin,Zhang, Xiaojing,Lin, Huijuan,et al. SUFU mediates EMT and Wnt/beta-catenin signaling pathway activation promoted by miRNA-324-5p in human gastric cancer[J]. CELL CYCLE,2020:14.
APA	Peng, Yin.,Zhang, Xiaojing.,Lin, Huijuan.,Deng, Shiqi.,Qin, Ying.,...&Jin, Zhe.(2020).SUFU mediates EMT and Wnt/beta-catenin signaling pathway activation promoted by miRNA-324-5p in human gastric cancer.CELL CYCLE,14.
MLA	Peng, Yin,et al."SUFU mediates EMT and Wnt/beta-catenin signaling pathway activation promoted by miRNA-324-5p in human gastric cancer".CELL CYCLE (2020):14.