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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.01096

Hepatocyte nuclear factor 3β plays a suppressive role in colorectal cancer progression

 Juan Wang1,  Hao Lu2,  Wei Wang3, Nanxin Zheng4, Yi Wang2, Zhiqian Hu2* and  Gang Ji5*
  • 1Xijing Hospital, Fourth Military Medical University, China
  • 2Department of General Surgery, Shanghai Changzheng Hospital, China
  • 3School of Pharmacy, Fourth Military Medical University, China
  • 4Department of Colorectal Surgery, Changhai Hospital, China
  • 5Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, China

Background and objective: Hepatocyte nuclear factor 3β (HNF3β) is a key transcription factor in the development of the gastrointestinal tract. However, only few studies have examined its’ expression, function and potential clinical significance in colorectal cancer tumorigenesis and progression.
Methods: HNF3β expression in colorectal cancer tissue samples of 174 patients was assessed by immunohistochemistry. The results were analyzed with respect to patients’ clinicopathological characteristics and survival. Following the in vitro cell transfection, MTT, wound healing, and Transwell assays were used to test cell proliferation, migration, and invasion respectively. Western blot was used to examine IL6, JAK1 and STAT3 protein expression. The potential for tumor formation was evaluated using a mouse xenograft model.
Results: HNF3β expression was lower in colon cancer tissue compared to normal tissue and correlated with UICC clinical stage (P = 0.001), depth of invasion (P = 0.004), regional lymph node metastasis (P = 0.007), distant metastasis (P = 0.048) and poor survival (P < 0.001) in patients with colorectal cancer. Furthermore HNF3β overexpression impeded proliferation, migration and invasion of SW480 cells via JAK-STAT3 signaling in vitro. Moreso, HNF3β overexpression showed a significant growth inhibition of subcutaneous xenograft tumors in vivo.
Conclusions: The results show that HNF3β acts as a suppressor of colorectal cancer progression and decreased HNF3 β expression is closely related to the poor prognosis. Thus, HNF3β may be a potential molecular target for inhibition of colorectal cancer cells and development of new anti-tumor therapies.

Keywords: Hepatocyte nuclear factor 3β, colorectal cancer, JAK-STAT signaling, cancer tumorigenesis, Cancer Progression

Received: 28 May 2019; Accepted: 04 Oct 2019.

Copyright: © 2019 Wang, Lu, Wang, Zheng, Wang, Hu and Ji. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Zhiqian Hu, Department of General Surgery, Shanghai Changzheng Hospital, Shanghai, China, huzq62@163.com
Mx. Gang Ji, Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China, jigangfmmu@163.com