INPP4B在胆囊癌患者及胆囊癌细胞中的表达及功能特征

2021年4月，安徽医科大学**附属医院普外科；安徽武警总队医院普外科(Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, People’s Republic of China；Department of General Surgery, the Armed Police Corps Hospital of Anhui,Hefei 230041, People’s Republic of China) Dengqun Sun老师研究团队在《BMC Cancer》上发表论文：

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

“INPP4B在胆囊癌患者及胆囊癌细胞中的表达及功能特征”

Abstract：

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.

摘要：

背景

INPP4B (INPP4B)是PI3K-Akt信号通路的负调控因子，在不同类型的癌症中发挥矛盾的作用。然而，INPP4B在人胆囊癌(GBC)中的生物学作用尚未阐明。在本研究中，我们研究了INPP4B在GBC患者和细胞系中的表达、临床意义和生物学功能。

方法

采用免疫组化方法检测INPP4B蛋白在胆囊癌组织和正常胆囊组织中的表达水平，并分析INPP4B蛋白在胆囊癌组织和正常胆囊组织中的临床意义。在GBC-SD和SGC-996细胞中敲低和过表达INPP4B，然后通过细胞增殖、克隆生成、凋亡检测、划伤创面愈合和transwell检测来鉴定INPP4B在体外的功能。

结果

与正常胆囊组织相比，人GBC组织中INPP4B表达上调，并与组织病理分化有关(p = 0.026)。本研究发现，与低分化肿瘤相比，INPP4B在高分化肿瘤中高表达(p = 0.022)。此外，我们发现INPP4B表达与GBC患者的总生存无关(p = 0.071)，也不是一个独立的预后因素。此外，当我们基于组织病理分化对INPP4B表达与GBC预后之间的关系进行分层时，我们发现INPP4B在GBC的进展中发挥着矛盾的作用，这取决于分化程度。此外，INPP4B敲低抑制GBC细胞的增殖、集落形成、迁移和侵袭，而INPP4B过表达在体外具有相反的作用，表明其作为癌蛋白的作用。

结论

这些发现提示INPP4B可能在GBC的预后中发挥双重作用，取决于分化程度，INPP4B可能在胆囊癌细胞中起致癌基因的作用。

该论文中，GBC细胞系GBC-sd和SGC996细胞的体外培养是使用Ausbian特级胎牛血清完成的。欲了解或购买Ausbian特级胎牛血清可以联系北京缔一生物400-166-8600.