Department of Digestive Disease and Gastrointestinal Motility Research Room, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Digestive Disease and Gastrointestinal Motility Research Room, Xi'an Jiaotong University, Xi'an, China.
Cell Prolif. 2019 May;52(3):e12585. doi: 10.1111/cpr.12585. Epub 2019 Feb 22.
The role of p62 in cancer is controversial. Evidence has shown that p62 is upregulated in different cancers and promotes tumour growth, such as in liver cancer and lung cancer. However, a recent study showed that the downregulation of p62 in hepatic stellate cells (HSCs) promotes hepatocellular carcinoma (HCC) development. How p62 is regulated in colorectal cancer (CRC) remains largely unknown. In this study, we aimed to investigate the roles and molecular mechanisms of p62 in CRC.
The expression levels of p62 in CRC tissues and adjacent non-tumour tissues were determined by immunohistochemistry (IHC). Stable p62-overexpression HCT116 cells and p62-knockdown SW480 cells were established with lentiviral vectors. The role of p62 in CRC was investigated in in vitro and in vivo functional studies. The relationship between p62 and the vitamin D receptor (VDR) was investigated by coimmunoprecipitation (Co-IP) assays.
p62 was significantly upregulated in CRC, and a high p62 level was an independent risk factor for a poor prognosis in CRC patients. p62 promoted CRC migration and invasion by inhibiting apoptosis and promoting cell proliferation in vitro, and p62 aggravated tumour growth and metastasis in vivo. Co-IP assays indicated that p62 interacts with the VDR and may target the NRF2-NQO1 axis.
Our study suggested that p62 functions as an oncogene in CRC through inhibiting apoptosis and promoting cell proliferation by interacting with the VDR.
p62 在癌症中的作用存在争议。有证据表明，p62 在不同的癌症中上调，并促进肿瘤生长，如肝癌和肺癌。然而，最近的一项研究表明，肝星状细胞（HSCs）中 p62 的下调促进了肝细胞癌（HCC）的发展。p62 在结直肠癌（CRC）中的调控方式在很大程度上尚不清楚。在本研究中，我们旨在研究 p62 在 CRC 中的作用和分子机制。
通过免疫组织化学（IHC）测定 CRC 组织和相邻非肿瘤组织中 p62 的表达水平。使用慢病毒载体建立稳定过表达 p62 的 HCT116 细胞和敲低 p62 的 SW480 细胞。通过体外和体内功能研究研究 p62 在 CRC 中的作用。通过共免疫沉淀（Co-IP）实验研究 p62 与维生素 D 受体（VDR）之间的关系。
p62 在 CRC 中显著上调，高 p62 水平是 CRC 患者预后不良的独立危险因素。p62 在体外通过抑制细胞凋亡和促进细胞增殖促进 CRC 迁移和侵袭，体内加重肿瘤生长和转移。Co-IP 实验表明，p62 与 VDR 相互作用，并可能靶向 NRF2-NQO1 轴。
我们的研究表明，p62 通过与 VDR 相互作用抑制细胞凋亡和促进细胞增殖，在 CRC 中发挥癌基因作用。
