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INPP4B exerts a dual role in gastric cancer progression and prognosis

Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates PI3K-Akt signalling and plays diverse roles in different types of cancer, but its role in gastric cancer (GC) is still unknown. Our study aimed to investigate the function and clinical relevance of INPP4B in GC. INPP4B expres...

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Autores principales: Wu, Youliang, Wang, Xiaodong, Lu, Yida, Wang, Huizhen, Wang, Mingliang, You, Yexiang, Su, Xiaoli, Sun, Dengqun, Sun, Yanjun, Li, Yongxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558642/
https://www.ncbi.nlm.nih.gov/pubmed/34729121
http://dx.doi.org/10.7150/jca.58397
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author Wu, Youliang
Wang, Xiaodong
Lu, Yida
Wang, Huizhen
Wang, Mingliang
You, Yexiang
Su, Xiaoli
Sun, Dengqun
Sun, Yanjun
Li, Yongxiang
author_facet Wu, Youliang
Wang, Xiaodong
Lu, Yida
Wang, Huizhen
Wang, Mingliang
You, Yexiang
Su, Xiaoli
Sun, Dengqun
Sun, Yanjun
Li, Yongxiang
author_sort Wu, Youliang
collection PubMed
description Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates PI3K-Akt signalling and plays diverse roles in different types of cancer, but its role in gastric cancer (GC) is still unknown. Our study aimed to investigate the function and clinical relevance of INPP4B in GC. INPP4B expression was detected in GC tissues and nontumour tissues. The effect of INPP4B on the phenotypic changes of AGS and BGC-823 cells was investigated in vitro. The activation of serum and glucocorticoid-regulated kinase 3 (SGK3) and AKT were used to evaluate the specific mechanistic function of INPP4B in GC cells. The messenger RNA (mRNA) and protein expression levels of INPP4B were decreased in GC tissues compared with nontumour tissues. INPP4B expression was associated with tumour-node-metastasis (TNM) stage and histopathological differentiation. In addition, high INPP4B expression in GC patients with large tumour size/low-undifferentiated/TNM's III-IV stage was correlated with a poor prognosis but it was correlated with a better prognosis in patients with small tumour size/high-moderate differentiated/TNM's I-II stage patients. In addition, INPP4B knockdown inhibited proliferation, clonal formation and migration and promoted cell apoptosis in vitro, while INPP4B overexpression led to the opposite effects. Mechanistically, we found that INPP4B overexpression enhanced the phosphorylation of SGK3 (p-SGK3) in AGS cells, whereas INPP4B knockdown enhanced the p-Akt level in BGC823 cells. These findings suggested that the expression of INPP4B in GC is lower than that in normal tissues. Based on stratification survival analysis and in vitro cell experiments, INPP4B may play dual roles as an oncogene and tumour suppressor gene in different tissue grades and clinical stages.
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spelling pubmed-85586422021-11-01 INPP4B exerts a dual role in gastric cancer progression and prognosis Wu, Youliang Wang, Xiaodong Lu, Yida Wang, Huizhen Wang, Mingliang You, Yexiang Su, Xiaoli Sun, Dengqun Sun, Yanjun Li, Yongxiang J Cancer Research Paper Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates PI3K-Akt signalling and plays diverse roles in different types of cancer, but its role in gastric cancer (GC) is still unknown. Our study aimed to investigate the function and clinical relevance of INPP4B in GC. INPP4B expression was detected in GC tissues and nontumour tissues. The effect of INPP4B on the phenotypic changes of AGS and BGC-823 cells was investigated in vitro. The activation of serum and glucocorticoid-regulated kinase 3 (SGK3) and AKT were used to evaluate the specific mechanistic function of INPP4B in GC cells. The messenger RNA (mRNA) and protein expression levels of INPP4B were decreased in GC tissues compared with nontumour tissues. INPP4B expression was associated with tumour-node-metastasis (TNM) stage and histopathological differentiation. In addition, high INPP4B expression in GC patients with large tumour size/low-undifferentiated/TNM's III-IV stage was correlated with a poor prognosis but it was correlated with a better prognosis in patients with small tumour size/high-moderate differentiated/TNM's I-II stage patients. In addition, INPP4B knockdown inhibited proliferation, clonal formation and migration and promoted cell apoptosis in vitro, while INPP4B overexpression led to the opposite effects. Mechanistically, we found that INPP4B overexpression enhanced the phosphorylation of SGK3 (p-SGK3) in AGS cells, whereas INPP4B knockdown enhanced the p-Akt level in BGC823 cells. These findings suggested that the expression of INPP4B in GC is lower than that in normal tissues. Based on stratification survival analysis and in vitro cell experiments, INPP4B may play dual roles as an oncogene and tumour suppressor gene in different tissue grades and clinical stages. Ivyspring International Publisher 2021-10-22 /pmc/articles/PMC8558642/ /pubmed/34729121 http://dx.doi.org/10.7150/jca.58397 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Wu, Youliang
Wang, Xiaodong
Lu, Yida
Wang, Huizhen
Wang, Mingliang
You, Yexiang
Su, Xiaoli
Sun, Dengqun
Sun, Yanjun
Li, Yongxiang
INPP4B exerts a dual role in gastric cancer progression and prognosis
title INPP4B exerts a dual role in gastric cancer progression and prognosis
title_full INPP4B exerts a dual role in gastric cancer progression and prognosis
title_fullStr INPP4B exerts a dual role in gastric cancer progression and prognosis
title_full_unstemmed INPP4B exerts a dual role in gastric cancer progression and prognosis
title_short INPP4B exerts a dual role in gastric cancer progression and prognosis
title_sort inpp4b exerts a dual role in gastric cancer progression and prognosis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558642/
https://www.ncbi.nlm.nih.gov/pubmed/34729121
http://dx.doi.org/10.7150/jca.58397
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