IL-8-mediated overexpression of ZNF274 promotes the proliferation and migration of colorectal cancer cells through the transactivation of MRPL40

Feng Du; Yijun Zhang; Xu Ji; Nan Zhang; Junxuan Xu; Tingting Ning; Si-an Xie; Si Liu; Peng Li; Shengtao Zhu

Heliyon (Aug 2023)

IL-8-mediated overexpression of ZNF274 promotes the proliferation and migration of colorectal cancer cells through the transactivation of MRPL40

Feng Du,
Yijun Zhang,
Xu Ji,
Nan Zhang,
Junxuan Xu,
Tingting Ning,
Si-an Xie,
Si Liu,
Peng Li,
Shengtao Zhu

Affiliations

Feng Du: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical, University, National Clinical Research Centre for Digestive Disease, Beijing, Digestive Disease Centre, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, 100050 Beijing, PR China
Yijun Zhang: Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, 100730, China
Xu Ji: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical, University, National Clinical Research Centre for Digestive Disease, Beijing, Digestive Disease Centre, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, 100050 Beijing, PR China
Nan Zhang: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical, University, National Clinical Research Centre for Digestive Disease, Beijing, Digestive Disease Centre, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, 100050 Beijing, PR China
Junxuan Xu: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical, University, National Clinical Research Centre for Digestive Disease, Beijing, Digestive Disease Centre, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, 100050 Beijing, PR China
Tingting Ning: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical, University, National Clinical Research Centre for Digestive Disease, Beijing, Digestive Disease Centre, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, 100050 Beijing, PR China
Si-an Xie: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical, University, National Clinical Research Centre for Digestive Disease, Beijing, Digestive Disease Centre, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, 100050 Beijing, PR China
Si Liu: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical, University, National Clinical Research Centre for Digestive Disease, Beijing, Digestive Disease Centre, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, 100050 Beijing, PR China
Peng Li: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical, University, National Clinical Research Centre for Digestive Disease, Beijing, Digestive Disease Centre, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, 100050 Beijing, PR China
Shengtao Zhu: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical, University, National Clinical Research Centre for Digestive Disease, Beijing, Digestive Disease Centre, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, 100050 Beijing, PR China; Corresponding author.

Journal volume & issue: Vol. 9, no. 8
p. e19046

Abstract

Read online

Background: Colorectal cancer (CRC) is one of the most prevalent malignant tumors with high morbidity and mortality rates worldwide. ZNF274, a member of the zinc-finger-protein family of transcription factors, is critical in chromosomal remodelling and tumorigenesis. However, the role of ZNF274 in CRC and the underlying molecular mechanisms remain unclear. Methods: Immunohistochemical analysis was performed to quantify the expression of ZNF274 in human CRC tissues. The Kaplan‒Meier method was used to analyse the relationship between ZNF274 expression and CRC prognosis. The correlation between ZNF274 expression and clinical features was analyzed using Cox regression analysis. Cell proliferation and migration were evaluated by CCK-8, colony formation, and Transwell assays. The limma R package was used to analyse IL-8-related differentially expressed genes in the GSE30364 dataset. The DAVID method was used to screen significantly enriched pathways. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter assays were performed to determine the transcriptional regulation of MRPL40 by ZNF274. Results: ZNF274 was overexpressed in CRC tissues and indicated poor prognosis. High ZNF274 expression was linked to larger tumor size, invasion, lymph node metastasis, and AJCC stage. Ectopic expression promoted CRC cell proliferation and migration. Mechanistically, MRPL40 was identified as the direct target gene that transactivates the expression of ZNF274. Moreover, IL-8 upregulated ZNF274 expression in a dose-dependent manner. Downregulation of either ZNF274 or MRPL40 expression abrogated the effect of IL-8 on promoting the proliferation and migration of CRC. Conclusion: This study revealed an oncogenic role of ZNF274 and the mechanism by which ZNF274 participated in IL-8-induced promotion of CRC progression. These findings demonstrate that ZNF274 could be used as a prognostic factor and potential therapeutic target for CRC treatment.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

About the journal

Abstract

Keywords