TY - JOUR AB - 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. AD - 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 AU - Zhang,Qiang AU - Yin,Yue AU - Zhao,Hongye AU - Shi,Yan AU - Zhang,Wei AU - Yang,Zhengpeng AU - Liu,Tingting AU - Huang,Yonghong AU - Yu,Zhanjiang DA - 2021/02/01 DO - 10.3892/ol.2020.12406 IS - 2 JO - Oncol Lett KW - prolyl 4‑hydroxylase subunit α1 colorectal cancer hypoxia inducible factor‑1α Wnt signaling PY - 2021 SN - 1792-1074 1792-1082 SP - 145 ST - P4HA1 regulates human colorectal cancer cells through HIF1α‑mediated Wnt signaling T2 - Oncology Letters TI - P4HA1 regulates human colorectal cancer cells through HIF1α‑mediated Wnt signaling UR - https://doi.org/10.3892/ol.2020.12406 VL - 21 ER -