OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell Carcinoma

Abstract Objective The effects of Otubain-2 (OTUB2) on the proliferation, invasion, and migration of esophageal squamous cell carcinoma (ESCC) were investigated by interfering with OTUB2 expression. Methods Bioinformatics analysis was used to analyze OTUB2 expression in esophageal carcinoma and inte...

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Main Authors: Li Liu, Hu Cheng, Min Ji, Liping Su, Ziyang Lu, Xiayun Hu, Yaling Guan, Jinling Xiao, Lijuan Ma, Wei Zhang, Hongwei Pu
Format: Article
Language:English
Published: BMC 2022-07-01
Series:Biological Procedures Online
Subjects:
Online Access:https://doi.org/10.1186/s12575-022-00169-9
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author Li Liu
Hu Cheng
Min Ji
Liping Su
Ziyang Lu
Xiayun Hu
Yaling Guan
Jinling Xiao
Lijuan Ma
Wei Zhang
Hongwei Pu
author_facet Li Liu
Hu Cheng
Min Ji
Liping Su
Ziyang Lu
Xiayun Hu
Yaling Guan
Jinling Xiao
Lijuan Ma
Wei Zhang
Hongwei Pu
author_sort Li Liu
collection DOAJ
description Abstract Objective The effects of Otubain-2 (OTUB2) on the proliferation, invasion, and migration of esophageal squamous cell carcinoma (ESCC) were investigated by interfering with OTUB2 expression. Methods Bioinformatics analysis was used to analyze OTUB2 expression in esophageal carcinoma and interactions between OTUB2 and YAP1/TAZ. Paraffin-embedded ESCC tissues (n = 183) were selected for immunohistochemical staining to detect OTUB2, YAP1, TAZ, CTGF and their relationship with clinicopathological parameters, then the survival prognosis of ESCC patients was analyzed. Immunofluorescence, western blotting, and qRT-PCR were used to evaluate OTUB2 in ESCC cell lines. Cell lines with the highest expression of OTUB2 were transfected with lentivirus to knockdown OTUB2 levels. Changes in KYSE150 cell proliferation, migration, and invasion were measured using CCK-8, wound healing, and clone formation assays. The Transwell test and flow cytometry identified OTUB2 targets and explored roles and mechanisms involved in ESCC. Effects of OTUB2 on YAP1/TAZ signaling were also observed. Results Bioinformatics analysis revealed OTUB2 was highly expressed in esophageal cancer and was associated with YAP1/TAZ. Immunohistochemistry showed that OTUB2 expression was increased in ESCC samples compared to parcancerous tissue. YAP1 and TAZ were higher expression in ESCC tissues, mainly localized in the nucleus. Compared with controls, the proliferation, migration, and invasion ability of KYSE150 cells after OTUB2 knockdown were significantly reduced (P < 0.05). The protein expression levels of YAP1, TAZ and CTGF decreased after knocking down the expression of OTUB2 (P < 0.05). OTUB2 knockdown in ESCC cell lines suppressed YAP1/TAZ signaling. Conclusions OTUB2 regulated the protein expression of YAP1/TAZ to promote cell proliferation, migration, invasion, and tumor development. Therefore, OTUB2 may represent a biomarker for ESCC and a potential target for ESCC treatment.
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spelling doaj.art-b47b56f4da9f427786450587b90588a92022-12-22T03:04:46ZengBMCBiological Procedures Online1480-92222022-07-0124111410.1186/s12575-022-00169-9OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell CarcinomaLi Liu0Hu Cheng1Min Ji2Liping Su3Ziyang Lu4Xiayun Hu5Yaling Guan6Jinling Xiao7Lijuan Ma8Wei Zhang9Hongwei Pu10Department of Pathology, First Affliated Hospital, Xinjiang Medical UniversityDepartment of Anesthesiology, First Affliated Hospital, Xinjiang Medical UniversitySchool of Basic Medicine, Xinjiang Medical UniversityDepartment of Pathology, First Affliated Hospital, Xinjiang Medical UniversityQilu HospitalShanghai Changhai HospitalSchool of Basic Medicine, Xinjiang Medical UniversitySchool of Basic Medicine, Xinjiang Medical UniversitySchool of Basic Medicine, Xinjiang Medical UniversityDepartment of Pathology, First Affliated Hospital, Xinjiang Medical UniversityDepartment of Discipline Construction, First Affliated Hospital, Xinjiang Medical UniversityAbstract Objective The effects of Otubain-2 (OTUB2) on the proliferation, invasion, and migration of esophageal squamous cell carcinoma (ESCC) were investigated by interfering with OTUB2 expression. Methods Bioinformatics analysis was used to analyze OTUB2 expression in esophageal carcinoma and interactions between OTUB2 and YAP1/TAZ. Paraffin-embedded ESCC tissues (n = 183) were selected for immunohistochemical staining to detect OTUB2, YAP1, TAZ, CTGF and their relationship with clinicopathological parameters, then the survival prognosis of ESCC patients was analyzed. Immunofluorescence, western blotting, and qRT-PCR were used to evaluate OTUB2 in ESCC cell lines. Cell lines with the highest expression of OTUB2 were transfected with lentivirus to knockdown OTUB2 levels. Changes in KYSE150 cell proliferation, migration, and invasion were measured using CCK-8, wound healing, and clone formation assays. The Transwell test and flow cytometry identified OTUB2 targets and explored roles and mechanisms involved in ESCC. Effects of OTUB2 on YAP1/TAZ signaling were also observed. Results Bioinformatics analysis revealed OTUB2 was highly expressed in esophageal cancer and was associated with YAP1/TAZ. Immunohistochemistry showed that OTUB2 expression was increased in ESCC samples compared to parcancerous tissue. YAP1 and TAZ were higher expression in ESCC tissues, mainly localized in the nucleus. Compared with controls, the proliferation, migration, and invasion ability of KYSE150 cells after OTUB2 knockdown were significantly reduced (P < 0.05). The protein expression levels of YAP1, TAZ and CTGF decreased after knocking down the expression of OTUB2 (P < 0.05). OTUB2 knockdown in ESCC cell lines suppressed YAP1/TAZ signaling. Conclusions OTUB2 regulated the protein expression of YAP1/TAZ to promote cell proliferation, migration, invasion, and tumor development. Therefore, OTUB2 may represent a biomarker for ESCC and a potential target for ESCC treatment.https://doi.org/10.1186/s12575-022-00169-9Esophageal squamous cell carcinomaOTUB2YAP1TAZBiomarker
spellingShingle Li Liu
Hu Cheng
Min Ji
Liping Su
Ziyang Lu
Xiayun Hu
Yaling Guan
Jinling Xiao
Lijuan Ma
Wei Zhang
Hongwei Pu
OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell Carcinoma
Biological Procedures Online
Esophageal squamous cell carcinoma
OTUB2
YAP1
TAZ
Biomarker
title OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell Carcinoma
title_full OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell Carcinoma
title_fullStr OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell Carcinoma
title_full_unstemmed OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell Carcinoma
title_short OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell Carcinoma
title_sort otub2 regulates yap1 taz to promotes the progression of esophageal squamous cell carcinoma
topic Esophageal squamous cell carcinoma
OTUB2
YAP1
TAZ
Biomarker
url https://doi.org/10.1186/s12575-022-00169-9
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