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

Abstract 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....

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Autores principales:	Yin Peng, Yidan Xu, Xiaojing Zhang, Shiqi Deng, Yuan Yuan, Xiaonuan Luo, Md Tofazzal Hossain, Xiaohui Zhu, Kaining Du, Fan Hu, Yang Chen, Shanshan Chang, Xianling Feng, Xinmin Fan, Hassan Ashktorab, Duane Smoot, Stephen J. Meltzer, Gangqiang Hou, Yanjie Wei, Song Li, Ying Qin, Zhe Jin
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	AXIN1 Wnt Translation circRNA Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/8c037b1b95034b6294d7f4a5465b9ed9
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spelling	oai:doaj.org-article:8c037b1b95034b6294d7f4a5465b9ed92021-12-05T12:03:24ZA novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/β-catenin signaling pathway to promote gastric cancer progression10.1186/s12943-021-01457-w1476-4598https://doaj.org/article/8c037b1b95034b6294d7f4a5465b9ed92021-12-01T00:00:00Zhttps://doi.org/10.1186/s12943-021-01457-whttps://doaj.org/toc/1476-4598Abstract 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 β-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.Yin PengYidan XuXiaojing ZhangShiqi DengYuan YuanXiaonuan LuoMd Tofazzal HossainXiaohui ZhuKaining DuFan HuYang ChenShanshan ChangXianling FengXinmin FanHassan AshktorabDuane SmootStephen J. MeltzerGangqiang HouYanjie WeiSong LiYing QinZhe JinBMCarticleAXIN1WntTranslationcircRNANeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Cancer, Vol 20, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	AXIN1 Wnt Translation circRNA Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	AXIN1 Wnt Translation circRNA Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yin Peng Yidan Xu Xiaojing Zhang Shiqi Deng Yuan Yuan Xiaonuan Luo Md Tofazzal Hossain Xiaohui Zhu Kaining Du Fan Hu Yang Chen Shanshan Chang Xianling Feng Xinmin Fan Hassan Ashktorab Duane Smoot Stephen J. Meltzer Gangqiang Hou Yanjie Wei Song Li Ying Qin Zhe Jin A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/β-catenin signaling pathway to promote gastric cancer progression
description	Abstract 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 β-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.
format	article
author	Yin Peng Yidan Xu Xiaojing Zhang Shiqi Deng Yuan Yuan Xiaonuan Luo Md Tofazzal Hossain Xiaohui Zhu Kaining Du Fan Hu Yang Chen Shanshan Chang Xianling Feng Xinmin Fan Hassan Ashktorab Duane Smoot Stephen J. Meltzer Gangqiang Hou Yanjie Wei Song Li Ying Qin Zhe Jin
author_facet	Yin Peng Yidan Xu Xiaojing Zhang Shiqi Deng Yuan Yuan Xiaonuan Luo Md Tofazzal Hossain Xiaohui Zhu Kaining Du Fan Hu Yang Chen Shanshan Chang Xianling Feng Xinmin Fan Hassan Ashktorab Duane Smoot Stephen J. Meltzer Gangqiang Hou Yanjie Wei Song Li Ying Qin Zhe Jin
author_sort	Yin Peng
title	A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/β-catenin signaling pathway to promote gastric cancer progression
title_short	A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/β-catenin signaling pathway to promote gastric cancer progression
title_full	A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/β-catenin signaling pathway to promote gastric cancer progression
title_fullStr	A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/β-catenin signaling pathway to promote gastric cancer progression
title_full_unstemmed	A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/β-catenin signaling pathway to promote gastric cancer progression
title_sort	novel protein axin1-295aa encoded by circaxin1 activates the wnt/β-catenin signaling pathway to promote gastric cancer progression
publisher	BMC
publishDate	2021
url	https://doaj.org/article/8c037b1b95034b6294d7f4a5465b9ed9
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A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/β-catenin signaling pathway to promote gastric cancer progression

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