Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China.
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX, 75390, USA.
BMC Cancer. 2021 Apr 20;21(1):433. doi: 10.1186/s12885-021-08143-6.
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.
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.
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.
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.
肌醇多磷酸 4-磷酸酶 II 型（INPP4B）是 PI3K-Akt 信号通路的负调节剂，在不同类型的癌症中发挥着矛盾的作用。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。
通过免疫组织化学检测胆囊癌组织和正常胆囊组织中 INPP4B 蛋白的表达水平，并分析 INPP4B 的临床意义。通过 INPP4B 在 GBC-SD 和 SGC-996 细胞中的敲低和过表达，以及细胞增殖、集落形成、凋亡检测、划痕愈合和 Transwell 测定，鉴定 INPP4B 在体外的功能。
与正常胆囊组织相比，INPP4B 在人 GBC 组织中上调，并与组织病理学分化相关（p=0.026）。我们观察到，INPP4B 在中高分化肿瘤中的表达高于低未分化肿瘤（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），也不是独立的预后因素。此外，当我们根据组织病理学分化将 INPP4B 表达与 GBC 预后的关系进行分层时，我们发现 INPP4B 在 GBC 进展中根据分化程度起着矛盾的作用。此外，INPP4B 敲低抑制 GBC 细胞的增殖、集落形成、迁移和侵袭，而 INPP4B 过表达在体外则有相反的效果，这表明其作为癌蛋白的作用。
这些发现表明，INPP4B 可能根据分化程度在 GBC 的预后中发挥双重作用，并且 INPP4B 可能在胆囊癌细胞中作为癌基因发挥作用。
