Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Biol Chem. 2022 Mar 31;403(10):917-928. doi: 10.1515/hsz-2022-0103. Print 2022 Sep 27.
Colorectal cancer (CRC) is a common cancer with poor prognosis. The research was designed to explore the role of PHF20L1 in angiogenesis and liver metastasis in CRC and discuss its molecular mechanism. Expression levels of PHF20L1, HIC1 and PAX2 in CRC tissues collected from CRC patients were detected using qRT-PCR, WB and immunohistochemical staining. CRC cells were transfected with PHF20L1, HIC1 and PAX2 overexpression or knockdown vectors and the proliferation, apoptosis, EMT and angiogenesis of the cells were determined. WB was utilized to assess protein levels of PHF20L1, HIC1, PAX2 and angiogenesis factor (ANGPT2, FGF1, PDGFA and VEGFA). The role of PHF20L1 regulating tumor formation and liver metastasis was detected as well. PHF20L1 was observed to express at a high level of CRC tissues. PHF20L1 promoted CRC cell growth, EMT and angiogenesis, and inhibited cell apoptosis. Knockdown of PHF20L1 had opposite effects on CRC cells. PHF20L1 negatively regulated HIC1 expression to promote PAX2 expression, thus promoting CRC cell progression. The results showed that PHF20L1 contributed to tumor formation and liver metastasis. PHF20L1 increases PAX2 expression to promote angiogenesis in CRC by inhibiting HIC1, therefore facilitating CRC cell EMT and liver metastasis. Our finding may provide a novel insight for CRC pathogenesis.
结直肠癌（CRC）是一种预后不良的常见癌症。本研究旨在探讨 PHF20L1 在 CRC 血管生成和肝转移中的作用，并探讨其分子机制。采用 qRT-PCR、WB 和免疫组织化学染色检测 CRC 患者CRC 组织中 PHF20L1、HIC1 和 PAX2 的表达水平。转染 PHF20L1、HIC1 和 PAX2 过表达或敲低载体，检测细胞增殖、凋亡、上皮间质转化（EMT）和血管生成。WB 检测 PHF20L1、HIC1、PAX2 和血管生成因子（ANGPT2、FGF1、PDGFA 和 VEGFA）的蛋白水平。还检测了 PHF20L1 调节肿瘤形成和肝转移的作用。结果发现，PHF20L1 在 CRC 组织中表达水平较高。PHF20L1 促进 CRC 细胞生长、EMT 和血管生成，抑制细胞凋亡。PHF20L1 敲低对 CRC 细胞则产生相反的作用。PHF20L1 负调控 HIC1 表达，促进 PAX2 表达，从而促进 CRC 细胞进展。结果表明，PHF20L1 促进肿瘤形成和肝转移。PHF20L1 通过抑制 HIC1 增加 PAX2 表达，促进 CRC 血管生成，从而促进 CRC 细胞 EMT 和肝转移。我们的发现可能为 CRC 的发病机制提供新的见解。
