Open Access

ARTICLE

The zinc figure protein ZNF575 impairs colorectal cancer growth via promoting p53 transcription

NING AN^1,#, HEQING PENG^2,#, MIN HOU³, DUOFENG SU², LIU WANG⁴, XIAOGANG SHEN^5,*, MING ZHANG^1,*

1 Cancer Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
2 School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
3 Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China
4 Department of Oncology, Chengdu Pidu District Hospital of traditional Chinese Medicine, Chengdu, China
5 Department of Gastrointestinal Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China

* Corresponding Authors: XIAOGANG SHEN. Email: ; MING ZHANG. Email:

Oncology Research 2023, 31(3), 307-316. https://doi.org/10.32604/or.2023.028564

Received 25 December 2022; Accepted 15 February 2023; Issue published 22 May 2023

Abstract

Zinc-finger proteins play different roles in cancer; however, the function of zinc-finger protein ZNF575 in cancer remains unclear. In the present study, we aimed to determine the function and expression of ZNF575 in colorectal cancer. Proliferation assay, colony formation assay, and tumor model in mice were used to investigate the function of ZNF575 after ectopic expression of ZNF575 in colorectal cancer (CRC) cells. RNA sequencing, ChIP, and luciferase assays were used to investigate the mechanism behind ZNF575 regulation of CRC cell growth. The expression of ZNF575 was determined by IHC staining in 150 pairs of malignant CRC tissues, followed by prognosis analysis. We indicated that ectopic expression of ZNF575 inhibited CRC cell proliferation, colony formation and promoted cell apoptosis in vitro. Tumor growth in CRC was also impaired by ZNF575 in mice. RNA sequencing, follow-up western blotting, and qPCR results demonstrated the increase of p53, BAK, and PUMA in ZNF575-expressing CRC cells. Further results indicated that ZNF575 directly targeted the p53 promoter and promoted the transcription of p53. Downregulation of ZNF575 was confirmed in malignant tissues, and ZNF575 expression was positively correlated with the prognosis of CRC patients. The present study demonstrated the function, underlying mechanism, expression, and the prognosis-predicting role of ZNF575 in CRC, which indicated that ZNF575 would be a potential prognostic predictor and therapeutic target for CRC and other cancers.

---

Graphical Abstract

---

Keywords

---