P4HA1 regulates human colorectal cancer cells through HIF1α‑mediated Wnt signaling

Zhang,Qiang; Yin,Yue; Zhao,Hongye; Shi,Yan; Zhang,Wei; Yang,Zhengpeng; Liu,Tingting; Huang,Yonghong; Yu,Zhanjiang

doi:10.3892/ol.2020.12406

P4HA1 regulates human colorectal cancer cells through HIF1α‑mediated Wnt signaling

Authors:
- Qiang Zhang
- Yue Yin
- Hongye Zhao
- Yan Shi
- Wei Zhang
- Zhengpeng Yang
- Tingting Liu
- Yonghong Huang
- Zhanjiang Yu
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Affiliations: Department of General Surgery, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China, Department of Scientific Research, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China, Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Biochemistry, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Endocrinology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China
Published online on: December 23, 2020 https://doi.org/10.3892/ol.2020.12406
Article Number: 145
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy that is associated with high levels of mortality. CRCs are often associated with an aberrant wingless‑type mouse mammary tumor virus integration site family (Wnt) signaling pathway known to be responsible for tumorigenesis and cancer progression. Other factors that contribute to CRC pathology include hypoxia, extracellular matrix and cellular microenvironment. In the present study, modulation of Wnt, a common molecular progenitor for CRC‑associated pathology was evaluated. CRC tissues and specific cell lines were found to exhibit increased expression levels of prolyl 4‑hydroxylase subunit α1 (P4HA1). P4HA1 expression was found to stabilize hypoxia inducible factor‑1α (HIF1α). The silencing of P4HA1 resulted in decreased cell proliferation, cell cycle arrest in the G1 phase, decreased tumorsphere formation, decreased tumorsphere volume, increased susceptibility to 5‑fluorouracil and increased caspase‑3 activity. However, P4HA1 silencing resulted in the activation and thus proteasomal degradation of β‑catenin, indicative of the abrogation of Wnt signaling pathway. Wnt is a critical signaling pathway and is activated in most CRCs. HIF1α is a poor prognostic marker in CRC. The present study provided preliminary evidence that HIF1α and the Wnt signaling pathway in CRC are modulated through P4HA1. P4HA1 may serve not just as a biomarker for CRC prognosis but may also be targeted for potential therapeutic intervention.

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