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Cell Prolif. 2019 Feb 22:e12585. doi: 10.1111/cpr.12585. [Epub ahead of print]

p62 functions as an oncogene in colorectal cancer through inhibiting apoptosis and promoting cell proliferation by interacting with the vitamin D receptor.

Author information

1
Department of Digestive Disease and Gastrointestinal Motility Research Room, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
2
Department of Digestive Disease and Gastrointestinal Motility Research Room, Xi'an Jiaotong University, Xi'an, China.
3
Clinical Research Center of Shanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi'an Jiaotong University, Xi'an, China.
4
National Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Xi'an Jiaotong University, Xi'an, China.
5
Department of Digestive Disease, Shanghai Pudong Hospital, Fudan Affiliated Pudong Medical Center, Shanghai, China.
6
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.

Abstract

OBJECTIVES:

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.

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

Our study suggested that p62 functions as an oncogene in CRC through inhibiting apoptosis and promoting cell proliferation by interacting with the VDR.

KEYWORDS:

SQSTM1/p62; apoptosis; colorectal cancer; proliferation; vitamin D receptor

PMID:
30793399
DOI:
10.1111/cpr.12585

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