Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Shanghai Colorectal Cancer Research Center, Shanghai, China.
Cancer Biol Ther. 2024 Dec 31;25(1):2361594. doi: 10.1080/15384047.2024.2361594. Epub 2024 Jun 10.
P4HA2 has been implicated in various malignant tumors; however, its expression and functional role in colorectal cancer (CRC) remain poorly elucidated. This study aims to investigate the involvement of P4HA2 in CRC metastasis and progression, uncovering the underlying mechanisms. In colorectal cancer (CRC), P4HA2 exhibited overexpression, and elevated levels of P4HA2 expression were associated with an unfavorable prognosis. Functional assays demonstrated P4HA2's regulation of cell proliferation, and epithelial-mesenchymal transition (EMT) both in vitro and in vivo. Additionally, the AGO1 expression was correlated with P4HA2, and depletion of AGO1 reversed the proliferation and EMT function induced by P4HA2. Chromatin immunoprecipitation (ChIP) and luciferase assays suggested that the transcription factor SP1 binds to the promoter sequence of P4HA2, activating its expression in CRC. This study unveiled SP1 as a transcriptional regulator of P4HA2 in CRC and AGO1 is a probable target of P4HA2. In conclusion, P4HA2 emerges as a potential prognostic biomarker and promising therapeutic target in colorectal cancer.
P4HA2 与多种恶性肿瘤有关;然而,其在结直肠癌(CRC)中的表达和功能作用仍未得到充分阐明。本研究旨在探讨 P4HA2 在 CRC 转移和进展中的作用,揭示其潜在的机制。在结直肠癌(CRC)中,P4HA2 表达上调,且 P4HA2 表达水平升高与预后不良相关。功能分析表明 P4HA2 可调控细胞增殖和上皮-间充质转化(EMT),无论是在体外还是体内。此外,AGO1 的表达与 P4HA2 相关,AGO1 的耗竭可逆转 P4HA2 诱导的增殖和 EMT 功能。染色质免疫沉淀(ChIP)和荧光素酶报告基因检测表明,转录因子 SP1 与 P4HA2 启动子序列结合,激活其在 CRC 中的表达。本研究揭示了 SP1 是 CRC 中 P4HA2 的转录调控因子,AGO1 可能是 P4HA2 的靶标。总之,P4HA2 有望成为结直肠癌的潜在预后标志物和治疗靶点。