INPP4B在膽囊癌患者及膽囊癌細胞中的表達及功能特征

2021年4月，安徽醫科大學**附屬醫院普外科；安徽武警總隊醫院普外科(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老師研究團隊在《BMC Cancer》上發表論文：

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

“INPP4B在膽囊癌患者及膽囊癌細胞中的表達及功能特征”

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信號通路的負調控因子，在不同類型的癌癥中發揮矛盾的作用。然而，INPP4B在人膽囊癌(GBC)中的生物學作用尚未闡明。在本研究中，我們研究了INPP4B在GBC患者和細胞系中的表達、臨床意義和生物學功能。

方法

采用免疫組化方法檢測INPP4B蛋白在膽囊癌組織和正常膽囊組織中的表達水平，并分析INPP4B蛋白在膽囊癌組織和正常膽囊組織中的臨床意義。在GBC-SD和SGC-996細胞中敲低和過表達INPP4B，然后通過細胞增殖、克隆生成、凋亡檢測、劃傷創面愈合和transwell檢測來鑒定INPP4B在體外的功能。

結果

與正常膽囊組織相比，人GBC組織中INPP4B表達上調，并與組織病理分化有關(p = 0.026)。本研究發現，與低分化腫瘤相比，INPP4B在高分化腫瘤中高表達(p = 0.022)。此外，我們發現INPP4B表達與GBC患者的總生存無關(p = 0.071)，也不是一個獨立的預后因素。此外，當我們基于組織病理分化對INPP4B表達與GBC預后之間的關系進行分層時，我們發現INPP4B在GBC的進展中發揮著矛盾的作用，這取決于分化程度。此外，INPP4B敲低抑制GBC細胞的增殖、集落形成、遷移和侵襲，而INPP4B過表達在體外具有相反的作用，表明其作為癌蛋白的作用。

結論

這些發現提示INPP4B可能在GBC的預后中發揮雙重作用，取決于分化程度，INPP4B可能在膽囊癌細胞中起致癌基因的作用。

該論文中，GBC細胞系GBC-sd和SGC996細胞的體外培養是使用Ausbian特級胎牛血清完成的。欲了解或購買Ausbian特級胎牛血清可以聯系北京締一生物400-166-8600.