Cargando…

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

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 interaction...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Li, Cheng, Hu, Ji, Min, Su, Liping, Lu, Ziyang, Hu, Xiayun, Guan, Yaling, Xiao, Jinling, Ma, Lijuan, Zhang, Wei, Pu, Hongwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290284/
https://www.ncbi.nlm.nih.gov/pubmed/35850645
http://dx.doi.org/10.1186/s12575-022-00169-9
_version_ 1784748865227849728
author Liu, Li
Cheng, Hu
Ji, Min
Su, Liping
Lu, Ziyang
Hu, Xiayun
Guan, Yaling
Xiao, Jinling
Ma, Lijuan
Zhang, Wei
Pu, Hongwei
author_facet Liu, Li
Cheng, Hu
Ji, Min
Su, Liping
Lu, Ziyang
Hu, Xiayun
Guan, Yaling
Xiao, Jinling
Ma, Lijuan
Zhang, Wei
Pu, Hongwei
author_sort Liu, Li
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12575-022-00169-9.
format Online
Article
Text
id pubmed-9290284
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-92902842022-07-19 OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell Carcinoma Liu, Li Cheng, Hu Ji, Min Su, Liping Lu, Ziyang Hu, Xiayun Guan, Yaling Xiao, Jinling Ma, Lijuan Zhang, Wei Pu, Hongwei Biol Proced Online Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12575-022-00169-9. BioMed Central 2022-07-18 /pmc/articles/PMC9290284/ /pubmed/35850645 http://dx.doi.org/10.1186/s12575-022-00169-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/ Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liu, Li
Cheng, Hu
Ji, Min
Su, Liping
Lu, Ziyang
Hu, Xiayun
Guan, Yaling
Xiao, Jinling
Ma, Lijuan
Zhang, Wei
Pu, Hongwei
OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell Carcinoma
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 Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290284/
https://www.ncbi.nlm.nih.gov/pubmed/35850645
http://dx.doi.org/10.1186/s12575-022-00169-9
work_keys_str_mv AT liuli otub2regulatesyap1taztopromotestheprogressionofesophagealsquamouscellcarcinoma
AT chenghu otub2regulatesyap1taztopromotestheprogressionofesophagealsquamouscellcarcinoma
AT jimin otub2regulatesyap1taztopromotestheprogressionofesophagealsquamouscellcarcinoma
AT suliping otub2regulatesyap1taztopromotestheprogressionofesophagealsquamouscellcarcinoma
AT luziyang otub2regulatesyap1taztopromotestheprogressionofesophagealsquamouscellcarcinoma
AT huxiayun otub2regulatesyap1taztopromotestheprogressionofesophagealsquamouscellcarcinoma
AT guanyaling otub2regulatesyap1taztopromotestheprogressionofesophagealsquamouscellcarcinoma
AT xiaojinling otub2regulatesyap1taztopromotestheprogressionofesophagealsquamouscellcarcinoma
AT malijuan otub2regulatesyap1taztopromotestheprogressionofesophagealsquamouscellcarcinoma
AT zhangwei otub2regulatesyap1taztopromotestheprogressionofesophagealsquamouscellcarcinoma
AT puhongwei otub2regulatesyap1taztopromotestheprogressionofesophagealsquamouscellcarcinoma