A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/beta-catenin signaling pathway to promote gastric cancer progression

doi:10.1186/s12943-021-01457-w

	A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/beta-catenin signaling pathway to promote gastric cancer progression
	Peng, Yin 1; Xu, Yidan 1; Zhang, Xiaojing 1; Deng, Shiqi 1; Yuan, Yuan 1; Luo, Xiaonuan 1; Hossain, Md Tofazzal 2,3,4; Zhu, Xiaohui 1; Du, Kaining 1; Hu, Fan 1; Chen, Yang 1; Chang, Shanshan 1; Feng, Xianling 1; Fan, Xinmin 1; Ashktorab, Hassan 5,6; Smoot, Duane 7; Meltzer, Stephen J.8,9; Hou, Gangqiang 10; Wei, Yanjie 2; Li, Song 11; Qin, Ying 12; Jin, Zhe 1
	2021-12-04
发表期刊	MOLECULAR CANCER
卷号	20 期号:1 页码:19
摘要	Background Circular RNA (circRNA), a subclass of non-coding RNA, plays a critical role in cancer tumorigenesis and metastasis. It has been suggested that circRNA acts as a microRNA sponge or a scaffold to interact with protein complexes; however, its full range of functions remains elusive. Recently, some circRNAs have been found to have coding potential. Methods To investigate the role of circRNAs in gastric cancer (GC), parallel sequencing was performed using five paired GC samples. Differentially expressed circAXIN1 was proposed to encode a novel protein. FLAG-tagged circRNA overexpression plasmid construction, immunoblotting, mass spectrometry, and luciferase reporter analyses were applied to confirm the coding potential of circAXIN1. Gain- and loss-of-function studies were conducted to study the oncogenic role of circAXIN1 and AXIN1-295aa on the proliferation, migration, invasion, and metastasis of GC cells in vitro and in vivo. The competitive interaction between AXIN1-295aa and adenomatous polyposis coli (APC) was investigated by immunoprecipitation analyses. Wnt signaling activity was observed using a Top/Fopflash assay, real-time quantitative RT-PCR, immunoblotting, immunofluorescence staining, and chromatin immunoprecipitation. Results CircAXIN1 is highly expressed in GC tissues compared with its expression in paired adjacent normal gastric tissues. CircAXIN1 encodes a 295 amino acid (aa) novel protein, which was named AXIN1-295aa. CircAXIN1 overexpression enhances the cell proliferation, migration, and invasion of GC cells, while the knockdown of circAXIN1 inhibits the malignant behaviors of GC cells in vitro and in vivo. Mechanistically, AXIN1-295aa competitively interacts with APC, leading to dysfunction of the "destruction complex" of the Wnt pathway. Released beta-catenin translocates to the nucleus and binds to the TCF consensus site on the promoter, inducing downstream gene expression. Conclusion CircAXIN1 encodes a novel protein, AXIN1-295aa. AXIN1-295aa functions as an oncogenic protein, activating the Wnt signaling pathway to promote GC tumorigenesis and progression, suggesting a potential therapeutic target for GC.
关键词	AXIN1 Wnt Translation circRNA
DOI	10.1186/s12943-021-01457-w
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[81772592] ; National Natural Science Foundation of China[31601028] ; National Natural Science Foundation of China[81871969] ; National Natural Science Foundation of China[82173290] ; National Natural Science Foundation of China[82172946] ; Medical Science and Technology Research Foundation of Guangdong Province[A2019211] ; Shenzhen Basic Research Fund[JCYJ20190808163801777] ; Shenzhen University Talent Program[000324] ; National Key Research and Development Program of China[2016YFB0201305] ; Youth Talent Support Program in Medical Center Shenzhen University ; High Quality University Construction 2nd phase[860-00000210]
WOS研究方向	Biochemistry & Molecular Biology ; Oncology
WOS类目	Biochemistry & Molecular Biology ; Oncology
WOS记录号	WOS:000726278300001
出版者	BMC
引用统计	被引频次：96[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/2XEOYT63/18137
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; Qin, Ying; Jin, Zhe
作者单位	1.Shenzhen Univ, Sch Med, Guangdong Prov Key Lab Genome Stabil & Dis Preven, Dept Pathol, 3688 Nanhai Ave, Shenzhen 518060, Guangdong, Peoples R China 2.Univ Chinese Acad Sci, 19 A Yuquan Rd, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Ctr High Performance Comp, Shenzhen Inst Adv Technol, Shenzhen 518000, Guangdong, Peoples R China 4.Bangabandhu Sheikh Mujibur Rahaman Sci & Technol, Dept Stat, Gopalganj 8100, Bangladesh 5.Howard Univ, Coll Med, Dept Med, Washington, DC 20060 USA 6.Howard Univ, Coll Med, Canc Ctr, Washington, DC 20060 USA 7.Meharry Med Ctr, Dept Med, Nashville, TN 37208 USA 8.Johns Hopkins Univ, Dept Med, GI Div, Sch Med, Baltimore, MD 21287 USA 9.Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA 10.Kangning Hosp, Dept Med Image Ctr, Shenzhen 518000, Guangdong, Peoples R China 11.Shenzhen Sci & Technol Dev Exchange Ctr, Shenzhen Sci & Technol Bldg, Shenzhen 518055, Guangdong, Peoples R China 12.Shenzhen Second Peoples Hosp, Dept Gastrointestinal Surg, Shenzhen 518000, Guangdong, Peoples R China
推荐引用方式 GB/T 7714	Peng, Yin,Xu, Yidan,Zhang, Xiaojing,et al. A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/beta-catenin signaling pathway to promote gastric cancer progression[J]. MOLECULAR CANCER,2021,20(1):19.
APA	Peng, Yin.,Xu, Yidan.,Zhang, Xiaojing.,Deng, Shiqi.,Yuan, Yuan.,...&Jin, Zhe.(2021).A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/beta-catenin signaling pathway to promote gastric cancer progression.MOLECULAR CANCER,20(1),19.
MLA	Peng, Yin,et al."A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/beta-catenin signaling pathway to promote gastric cancer progression".MOLECULAR CANCER 20.1(2021):19.