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Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells

BACKGROUND: Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of the PI3K-Akt signalling pathway and plays a contradictory role in different types of cancers. However, the its biological role played by INPP4B in human gallbladder cancer (GBC) has not been elucidated. In t...

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Autores principales: Wu, Youliang, Meng, Delong, Xu, Xin, Bao, Junjun, You, Yexiang, Sun, Yanjun, Li, Yongxiang, Sun, Dengqun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056679/
https://www.ncbi.nlm.nih.gov/pubmed/33879096
http://dx.doi.org/10.1186/s12885-021-08143-6
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author Wu, Youliang
Meng, Delong
Xu, Xin
Bao, Junjun
You, Yexiang
Sun, Yanjun
Li, Yongxiang
Sun, Dengqun
author_facet Wu, Youliang
Meng, Delong
Xu, Xin
Bao, Junjun
You, Yexiang
Sun, Yanjun
Li, Yongxiang
Sun, Dengqun
author_sort Wu, Youliang
collection PubMed
description BACKGROUND: Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of the PI3K-Akt signalling pathway and plays a contradictory role in different types of cancers. However, the its biological role played by INPP4B in human gallbladder cancer (GBC) has not been elucidated. In this study, we investigated the expression, clinical significance and biological function of INPP4B in GBC patients and cell lines. METHODS: The INPP4B protein expression levels in gallbladder cancer tissues and normal gallbladder tissues were detected by immunohistochemistry, and the clinical significance of INPP4B was analysed. Knockdown and overexpression of INPP4B in GBC-SD and SGC-996 cells followed by cell proliferation, clonogenic, apoptosis detection, scratch wound-healing and transwell assays were used to identify INPP4B function in vitro. RESULTS: INPP4B was up-regulated in human GBC tissues compared with normal gallbladder tissues and was related to histopathological differentiation (p = 0.026). Here, we observed that INPP4B was highly expressed in high-moderately differentiated tumours compared with low-undifferentiated tumours (p = 0.022). Additionally, we found that INPP4B expression was not associated with overall survival of GBC patients (p = 0.071) and was not an independent prognostic factor. Furthermore, when we stratified the relationship between INPP4B expression and the prognosis of GBC based on histopathological differentiation, we found that INPP4B played a contradictory role in GBC progression depending on the degree of differentiation. In addition, INPP4B knockdown inhibited the proliferation, colony formation, migration and invasion in GBC cells, while INPP4B overexpression had the opposite effects in vitro, which indicates its role as an oncoprotein. CONCLUSIONS: These findings suggested that INPP4B may play a dual role in the prognosis of GBC depending on the degree of differentiation and that INPP4B might act as an oncogene in gallbladder cancer cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08143-6.
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spelling pubmed-80566792021-04-21 Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells Wu, Youliang Meng, Delong Xu, Xin Bao, Junjun You, Yexiang Sun, Yanjun Li, Yongxiang Sun, Dengqun BMC Cancer Research Article BACKGROUND: Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of the PI3K-Akt signalling pathway and plays a contradictory role in different types of cancers. However, the its biological role played by INPP4B in human gallbladder cancer (GBC) has not been elucidated. In this study, we investigated the expression, clinical significance and biological function of INPP4B in GBC patients and cell lines. METHODS: The INPP4B protein expression levels in gallbladder cancer tissues and normal gallbladder tissues were detected by immunohistochemistry, and the clinical significance of INPP4B was analysed. Knockdown and overexpression of INPP4B in GBC-SD and SGC-996 cells followed by cell proliferation, clonogenic, apoptosis detection, scratch wound-healing and transwell assays were used to identify INPP4B function in vitro. RESULTS: INPP4B was up-regulated in human GBC tissues compared with normal gallbladder tissues and was related to histopathological differentiation (p = 0.026). Here, we observed that INPP4B was highly expressed in high-moderately differentiated tumours compared with low-undifferentiated tumours (p = 0.022). Additionally, we found that INPP4B expression was not associated with overall survival of GBC patients (p = 0.071) and was not an independent prognostic factor. Furthermore, when we stratified the relationship between INPP4B expression and the prognosis of GBC based on histopathological differentiation, we found that INPP4B played a contradictory role in GBC progression depending on the degree of differentiation. In addition, INPP4B knockdown inhibited the proliferation, colony formation, migration and invasion in GBC cells, while INPP4B overexpression had the opposite effects in vitro, which indicates its role as an oncoprotein. CONCLUSIONS: These findings suggested that INPP4B may play a dual role in the prognosis of GBC depending on the degree of differentiation and that INPP4B might act as an oncogene in gallbladder cancer cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08143-6. BioMed Central 2021-04-20 /pmc/articles/PMC8056679/ /pubmed/33879096 http://dx.doi.org/10.1186/s12885-021-08143-6 Text en © The Author(s) 2021 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 Article
Wu, Youliang
Meng, Delong
Xu, Xin
Bao, Junjun
You, Yexiang
Sun, Yanjun
Li, Yongxiang
Sun, Dengqun
Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells
title Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells
title_full Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells
title_fullStr Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells
title_full_unstemmed Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells
title_short Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells
title_sort expression and functional characterization of inpp4b in gallbladder cancer patients and gallbladder cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056679/
https://www.ncbi.nlm.nih.gov/pubmed/33879096
http://dx.doi.org/10.1186/s12885-021-08143-6
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