Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells

Ubiquitin-proteasome pathway has emerged as therapeutic targets for cancer. GEPIA database analysis showed that the expression of ubiquitin-associated protein 2 like (UBAP2L) in gastric cancer specimens was significantly higher than that in non-tumor tissue, and its high expression is associated wit...

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Autores principales:	Sihan Lin, Zhiyong Yan, Qiaofei Tang, Shuang Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	ubap2l gastric cancer mirna growth migration invasion Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/bc46f5dfb0054ae0bd1faed1a62be774
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spelling	oai:doaj.org-article:bc46f5dfb0054ae0bd1faed1a62be7742021-12-01T14:41:00ZUbiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells2165-59792165-598710.1080/21655979.2021.1982308https://doaj.org/article/bc46f5dfb0054ae0bd1faed1a62be7742021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1982308https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Ubiquitin-proteasome pathway has emerged as therapeutic targets for cancer. GEPIA database analysis showed that the expression of ubiquitin-associated protein 2 like (UBAP2L) in gastric cancer specimens was significantly higher than that in non-tumor tissue, and its high expression is associated with poor survival of gastric cancer patients. This study aims to investigate the role of UBAP2L in gastric cancer. Real-time PCR and western blot results showed that UBAP2L expression was upregulated in gastric cancer cell lines. Loss- and gain-of-function experiments demonstrated that silencing of UBAP2L inhibited proliferation, migration and invasion, and induced apoptosis of gastric cancer cells, and overexpression of UBAP2L played opposite roles. Nude mice inoculated with UBAP2L-silenced gastric cancer cells generated smaller xenografted tumors in vivo. Furthermore, UBAP2L activated Wnt/β-catenin signaling – the accumulation of nuclear β-catenin and the expression of its downstream targets (cyclin D1, AXIN-2 and c-MYC) was facilitated, whereas knockdown of UBAP2L deactivated this signaling. The tumor-suppressing effect of UBAP2L silencing was abolished by forced activation of β-cateninS33A. UBAP2L has been confirmed as a novel and direct target of miR-148b-3p. The anti-tumor effect of miR-148b-3p was partly reversed by UBAP2L overexpression. The expression of miR-148b-3p was negatively correlated with that of UBAP2L in gastric cancer samples. Overall, our study indicates that UBAP2L is required to maintain malignant behavior of gastric cancer cells, which involves the activation of Wnt/β-catenin signaling pathway. We propose UBAP2L as a potential therapeutic target against gastric cancer.Sihan LinZhiyong YanQiaofei TangShuang ZhangTaylor & Francis Grouparticleubap2lgastric cancermirnagrowthmigrationinvasionBiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 2, Pp 10232-10245 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ubap2l gastric cancer mirna growth migration invasion Biotechnology TP248.13-248.65
spellingShingle	ubap2l gastric cancer mirna growth migration invasion Biotechnology TP248.13-248.65 Sihan Lin Zhiyong Yan Qiaofei Tang Shuang Zhang Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells
description	Ubiquitin-proteasome pathway has emerged as therapeutic targets for cancer. GEPIA database analysis showed that the expression of ubiquitin-associated protein 2 like (UBAP2L) in gastric cancer specimens was significantly higher than that in non-tumor tissue, and its high expression is associated with poor survival of gastric cancer patients. This study aims to investigate the role of UBAP2L in gastric cancer. Real-time PCR and western blot results showed that UBAP2L expression was upregulated in gastric cancer cell lines. Loss- and gain-of-function experiments demonstrated that silencing of UBAP2L inhibited proliferation, migration and invasion, and induced apoptosis of gastric cancer cells, and overexpression of UBAP2L played opposite roles. Nude mice inoculated with UBAP2L-silenced gastric cancer cells generated smaller xenografted tumors in vivo. Furthermore, UBAP2L activated Wnt/β-catenin signaling – the accumulation of nuclear β-catenin and the expression of its downstream targets (cyclin D1, AXIN-2 and c-MYC) was facilitated, whereas knockdown of UBAP2L deactivated this signaling. The tumor-suppressing effect of UBAP2L silencing was abolished by forced activation of β-cateninS33A. UBAP2L has been confirmed as a novel and direct target of miR-148b-3p. The anti-tumor effect of miR-148b-3p was partly reversed by UBAP2L overexpression. The expression of miR-148b-3p was negatively correlated with that of UBAP2L in gastric cancer samples. Overall, our study indicates that UBAP2L is required to maintain malignant behavior of gastric cancer cells, which involves the activation of Wnt/β-catenin signaling pathway. We propose UBAP2L as a potential therapeutic target against gastric cancer.
format	article
author	Sihan Lin Zhiyong Yan Qiaofei Tang Shuang Zhang
author_facet	Sihan Lin Zhiyong Yan Qiaofei Tang Shuang Zhang
author_sort	Sihan Lin
title	Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells
title_short	Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells
title_full	Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells
title_fullStr	Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells
title_full_unstemmed	Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells
title_sort	ubiquitin-associated protein 2 like (ubap2l) enhances growth and metastasis of gastric cancer cells
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/bc46f5dfb0054ae0bd1faed1a62be774
work_keys_str_mv	AT sihanlin ubiquitinassociatedprotein2likeubap2lenhancesgrowthandmetastasisofgastriccancercells AT zhiyongyan ubiquitinassociatedprotein2likeubap2lenhancesgrowthandmetastasisofgastriccancercells AT qiaofeitang ubiquitinassociatedprotein2likeubap2lenhancesgrowthandmetastasisofgastriccancercells AT shuangzhang ubiquitinassociatedprotein2likeubap2lenhancesgrowthandmetastasisofgastriccancercells
_version_	1718405017046614016

Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells

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