Dual activation of Hedgehog and Wnt/beta-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer

	Dual activation of Hedgehog and Wnt/beta-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer
	Peng, Yin 1,2; Zhang, Xiaojing 1,2,3; Lin, Huijuan 4,5; Deng, Shiqi 1; Qin, Ying 6; He, Jieqiong 1; Hu, Fan 1; Zhu, Xiaohui 1; Feng, Xianling 1; Wang, Jian 5; Wei, Yanjie 7; Fan, Xinmin 1; Lin, Huan 8; Ashktorab, Hassan 9,10; Smoot, Duane 11; Lv, Yansi 1; Li, Song 12; Meltzer, Stephen J.13,14; Jin, Zhe 1,2
	2021-04-15
发表期刊	AGING-US
ISSN	1945-4589
卷号	13 期号:7 页码:10749-10769
摘要	Mounting evidence has shown that miRNA-150 expression is upregulated in gastric cancer (GC) and is associated with gastric carcinogenesis, but the underlying oncogenic mechanism remains elusive. Here, we discovered that miRNA-150 targets the tumor suppressor SUFU to promote cell proliferation, migration, and the epithelial-mesenchymal transition (EMT) via the dual activation of Hedgehog (Hh) and Wnt signaling. MiRNA-150 was highly expressed in GC tissues and cell lines, and the level of this miRNA was negatively related to that of SUFU. In addition, both the miRNA-150 and SUFU levels were associated with tumor differentiation. Furthermore, miRNA-150 activated GC cell proliferation and migration in vitro. We found that miRNA-150 inhibitors repressed not only Wnt signaling by promoting cytoplasmic beta-catenin localization, but also repressed Hh signaling and EMT. MiRNA-150 inhibition also resulted in significant tumor volume reductions in vivo, suggesting the potential application of miRNA-150 inhibitors in GC therapy. The expression of genes downstream of Hh and Wnt signaling was also reduced in tumors treated with miRNA-150 inhibitors. Notably, anti-SUFU siRNAs rescued the inhibitory effects of miRNA-150 inhibitors on Wnt signaling, Hh activation, EMT, cell proliferation, cell migration, and colony formation. Taken together, these findings indicate that miRNA-150 is oncogenic and promotes GC cell proliferation, migration, and EMT by activating Wnt and Hh signaling via the suppression of SUFU expression.
关键词	miRNA-150 SUFU Wnt/beta-catenin hedgehog EMT
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[31601028] ; National Natural Science Foundation of China[81772592] ; National Natural Science Foundation of China[81871969] ; Nature Science Foundation of Guangdong Province[2017A030313144] ; Nature Science Foundation of Guangdong Province[2017A030313479] ; Nature Science Foundation of Guangdong Province[2017B030301016] ; Medical science and technology research foundation of Guangdong Province[A2019211] ; Medical science and technology research foundation of Guangdong Province[A2018170] ; Shenzhen Basic Research Fund[JCYJ20170818142852491] ; Shenzhen Basic Research Fund[JCYJ20170413093358429] ; Shenzhen Basic Research Fund[JCYJ20190808163801777] ; Shenzhen University Talent program[000324] ; Startup Fund of Shenzhen University[2018015] ; High Quality University Construction 2nd phase[860-00000210] ; National Key Research and Development Program of China[2016YFB0201305] ; Youth talent support program in medical center Shenzhen University
WOS研究方向	Cell Biology ; Geriatrics & Gerontology
WOS类目	Cell Biology ; Geriatrics & Gerontology
WOS记录号	WOS:000657258800016
出版者	IMPACT JOURNALS LLC
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/2XEOYT63/17536
专题	中国科学院计算技术研究所期刊论文_英文
通讯作者	Li, Song; Jin, Zhe
作者单位	1.Shenzhen Univ, Dept Pathol, Guangdong Key Lab Genome Stabil & Dis Prevent, Sch Med, Shenzhen 518060, Guangdong, Peoples R China 2.Shenzhen Univ, Hlth Sci Ctr, Dept Pathol, Guangdong Prov Key Lab Reg Immun & Dis, Shenzhen 518060, Guangdong, Peoples R China 3.Dept Pathol, Guangdong Prov Key Lab Mol Oncol Pathol, Guangzhou 510515, Guangdong, Peoples R China 4.Guangdong Women & Children Hosp, Dept Ultrasound, Guangzhou 510000, Guangdong, Peoples R China 5.Guangzhou Med Univ, Dept Pathol & Pathophysiol, Guangzhou 510000, Guangdong, Peoples R China 6.Shenzhen Univ, Dept Gastrointestinal Surg, Affiliated Hosp 1, Shenzhen 518000, Guangdong, Peoples R China 7.Shenzhen Inst Adv Technol, Ctr High Performance Comp, Shenzhen 518000, Guangdong, Peoples R China 8.Shenzhen Univ, Dept Vasc Surg, Affiliated Hosp 1, Shenzhen 518060, Guangdong, Peoples R China 9.Howard Univ, Coll Med, Dept Med, Washington, DC 20060 USA 10.Howard Univ, Coll Med, Canc Ctr, Washington, DC 20060 USA 11.Meharry Med Ctr, Dept Med, Nashville, TN 37208 USA 12.Shenzhen Sci & Technol Dev Exchange Ctr, Shenzhen 518060, Guangdong, Peoples R China 13.Johns Hopkins Univ, Dept Med, GI Div, Sch Med, Baltimore, MD 21287 USA 14.Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA
推荐引用方式 GB/T 7714	Peng, Yin,Zhang, Xiaojing,Lin, Huijuan,et al. Dual activation of Hedgehog and Wnt/beta-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer[J]. AGING-US,2021,13(7):10749-10769.
APA	Peng, Yin.,Zhang, Xiaojing.,Lin, Huijuan.,Deng, Shiqi.,Qin, Ying.,...&Jin, Zhe.(2021).Dual activation of Hedgehog and Wnt/beta-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer.AGING-US,13(7),10749-10769.
MLA	Peng, Yin,et al."Dual activation of Hedgehog and Wnt/beta-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer".AGING-US 13.7(2021):10749-10769.