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Research article
Expression and Functional Identification of INPP4B in Gallbladder Cancer Patients and Gallbladder Cancer Cells
Dengqun Sun
the Armed Police Corps Hospital of Anhui
Corresponding Author
ORCiD: https://orcid.org/0000-0002-2891-722X
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Purpose: Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of PI3K-Akt signaling pathway and plays a contradictory role in different types of cancers. However, its biological role in human gallbladder cancer (GBC) remain unclear. Here we aimed to investigate the expression, clinical significance and biological function of INPP4B in GBC clinical dates and GBC 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 analyzed. Knockdown and overexpression of INPP4B on GBC-SD and SGC-996 cells were used to identify INPP4B function in vitro, using cell proliferation assay, clonogenic assay, apoptosis detection, cratch wound-healing assay and transwell assay.
Results: INPP4B was up-regulated in human GBC tissues compared with normal gallbladder tissues, and was related to histopathological differentiation. Here, we observed that INPP4B was highly expressed in high-moderate differentiated compared to low-undifferentiated. Additionally, we found that INPP4B expression was not associated with overall survival in GBC patients and was not an independent prognostic factor. Furthermore, when we stratified the relationship between INPP4B expression and prognosis of GBC from histopathological differentiation, we found that INPP4B played a contradictory role in GBC progression at different degrees of differentiation. In addition, INPP4B knockdown inhibited tumorigenicity in vitro, and INPP4B overexpression induced tumorigenicity in vitro, which may play a role as an oncoprotein.
Conclusions: These findings implicated that INPP4B may play a dual role in the prognosis of GBC with different degrees of differentiation, and might act as an oncogene in gallbladder cancer cells.
Keywords
gallbladder cancer, INPP4B, tumor suppressor gene, oncogene, prognostic biomarker
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On 04 Oct, 2020
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This preprint is under consideration at BMC Cancer. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Expression and Functional Identification of INPP4B in Gallbladder Cancer Patients and Gallbladder Cancer Cells
Dengqun Sun
the Armed Police Corps Hospital of Anhui
Corresponding Author
ORCiD: https://orcid.org/0000-0002-2891-722X
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 28 Sep, 2020
No community comments so far
Editorial decision: Minor revision
On 03 Nov, 2020
Review #1 received
Received 18 Oct, 2020
Review #2 received
Received 17 Oct, 2020
Reviewer #1 agreed
On 04 Oct, 2020
Reviewer #2 agreed
On 04 Oct, 2020
Editor assigned
On 30 Sep, 2020
Reviewers invited
Invitations sent on 30 Sep, 2020
Submission checks complete
On 25 Sep, 2020
Editor invited
On 22 Sep, 2020
First submitted
On 12 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Purpose: Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of PI3K-Akt signaling pathway and plays a contradictory role in different types of cancers. However, its biological role in human gallbladder cancer (GBC) remain unclear. Here we aimed to investigate the expression, clinical significance and biological function of INPP4B in GBC clinical dates and GBC 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 analyzed. Knockdown and overexpression of INPP4B on GBC-SD and SGC-996 cells were used to identify INPP4B function in vitro, using cell proliferation assay, clonogenic assay, apoptosis detection, cratch wound-healing assay and transwell assay.
Results: INPP4B was up-regulated in human GBC tissues compared with normal gallbladder tissues, and was related to histopathological differentiation. Here, we observed that INPP4B was highly expressed in high-moderate differentiated compared to low-undifferentiated. Additionally, we found that INPP4B expression was not associated with overall survival in GBC patients and was not an independent prognostic factor. Furthermore, when we stratified the relationship between INPP4B expression and prognosis of GBC from histopathological differentiation, we found that INPP4B played a contradictory role in GBC progression at different degrees of differentiation. In addition, INPP4B knockdown inhibited tumorigenicity in vitro, and INPP4B overexpression induced tumorigenicity in vitro, which may play a role as an oncoprotein.
Conclusions: These findings implicated that INPP4B may play a dual role in the prognosis of GBC with different degrees of differentiation, and might act as an oncogene in gallbladder cancer cells.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5