Wu Youliang, Wang Xiaodong, Lu Yida, Wang Huizhen, Wang Mingliang, You Yexiang, Su Xiaoli, Sun Dengqun, Sun Yanjun, Li Yongxiang
Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, People's Republic of China.
Department of Endoscopy Center, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, People's Republic of China.
J Cancer. 2021 Oct 22;12(23):7201-7213. doi: 10.7150/jca.58397. eCollection 2021.
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 on the phenotypic changes of AGS and BGC-823 cells was investigated . The activation of serum and glucocorticoid-regulated kinase 3 (SGK3) and AKT were used to evaluate the specific mechanistic function of in GC cells. The messenger RNA (mRNA) and protein expression levels of 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, knockdown inhibited proliferation, clonal formation and migration and promoted cell apoptosis , while overexpression led to the opposite effects. Mechanistically, we found that overexpression enhanced the phosphorylation of SGK3 (p-SGK3) in AGS cells, whereas 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 cell experiments, may play dual roles as an oncogene and tumour suppressor gene in different tissue grades and clinical stages.
II型肌醇多磷酸4-磷酸酶（INPP4B）负向调节PI3K-Akt信号通路，并在不同类型的癌症中发挥多种作用，但其在胃癌（GC）中的作用仍不清楚。我们的研究旨在探讨INPP4B在GC中的功能及临床相关性。检测了GC组织和非肿瘤组织中INPP4B的表达。研究了[此处原文缺失相关内容]对AGS和BGC-823细胞表型变化的影响。采用血清和糖皮质激素调节激酶3（SGK3）和AKT的激活来评估[此处原文缺失相关内容]在GC细胞中的具体机制功能。与非肿瘤组织相比，GC组织中[此处原文缺失相关内容]的信使核糖核酸（mRNA）和蛋白质表达水平降低。INPP4B表达与肿瘤-淋巴结-转移（TNM）分期和组织病理学分化相关。此外，肿瘤体积大/低分化/TNM III-IV期的GC患者中INPP4B高表达与预后不良相关，但在肿瘤体积小/高中分化/TNM I-II期患者中与较好的预后相关。此外，[此处原文缺失相关内容]敲低抑制了细胞增殖、克隆形成和迁移，并促进了细胞凋亡，而[此处原文缺失相关内容]过表达则产生相反的效果。机制上，我们发现[此处原文缺失相关内容]过表达增强了AGS细胞中SGK3的磷酸化（p-SGK3），而[此处原文缺失相关内容]敲低增强了BGC823细胞中p-Akt水平。这些发现表明，GC中INPP4B的表达低于正常组织。基于分层生存分析和[此处原文缺失相关内容]细胞实验，[此处原文缺失相关内容]在不同组织分级和临床分期中可能作为癌基因和抑癌基因发挥双重作用。
