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Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells
Youliang Wu1, Delong Meng2, Xin Xu1
1Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China.
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.
Insights
Inositol polyphosphate 4-phosphatase type II (INPP4B) is upregulated in gallbladder cancer (GBC) and acts as an oncoprotein. Its role in GBC prognosis is dual, depending on tumor differentiation.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Inositol polyphosphate 4-phosphatase type II (INPP4B) regulates the PI3K-Akt pathway and has varied roles in cancer.
- Its specific function in human gallbladder cancer (GBC) remains unclear.
Purpose of the Study:
- To investigate the expression, clinical significance, and biological function of INPP4B in GBC.
Main Methods:
- Immunohistochemistry used to detect INPP4B protein in GBC and normal tissues.
- In vitro assays (proliferation, clonogenic, apoptosis, migration, invasion) performed after INPP4B knockdown or overexpression in GBC cell lines.
Main Results:
- INPP4B was upregulated in GBC tissues and correlated with histopathological differentiation.
- INPP4B expression did not significantly correlate with overall survival or act as an independent prognostic factor.
- INPP4B knockdown inhibited GBC cell proliferation, colony formation, migration, and invasion, while overexpression enhanced these processes.
Conclusions:
- INPP4B exhibits a dual role in GBC prognosis, contingent on tumor differentiation.
- INPP4B functions as an oncogene in gallbladder cancer cells.
