Zinc finger protein 263 promotes colorectal cancer cell progression by activating STAT3 and enhancing chemoradiotherapy resistance.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Cell Proliferation* ; Colorectal Neoplasms*/pathology ; Colorectal Neoplasms*/genetics ; Colorectal Neoplasms*/metabolism ; Gene Expression Regulation, Neoplastic* ; STAT3 Transcription Factor*/metabolism ; DNA-Binding Proteins*/genetics ; DNA-Binding Proteins*/metabolism; Female ; Humans ; Male ; Middle Aged ; Cell Line, Tumor ; Cell Movement ; Chemoradiotherapy/methods ; Disease Progression ; Drug Resistance, Neoplasm/genetics ; Epithelial-Mesenchymal Transition/genetics

Zinc finger protein 263 (ZNF263) is frequently upregulated in various tumor types; however, its function and regulatory mechanism in colorectal cancer (CRC) have not yet been elucidated. In this study, the expression of ZNF263 was systematically examined using data from The Cancer Genome Atlas database and samples from patients with CRC. The results indicated that high expression of ZNF263 in CRC tissues is significantly associated with tumor grade, lymph node metastasis and disant metastasis. Additionally, overexpression of ZNF263 significantly promoted the proliferation, invasion, migration, and epithelial-mesenchymal transition of CRC cells, while also increasing signal transducer and activator of transcription 3 (STAT3) expression and mRNA stability. Conversely, knockdown of ZNF263 inhibited the malignant behavior of CRC cells and decreased STAT3 expression and mRNA stability. Further mechanism studies using chromatin immunoprecipitation (CHIP) and luciferase assays verified that ZNF263 directly binds to the STAT3 promoter. Rescue experiments demonstrated that the knockdown or overexpression of STAT3 could significantly reverse the effects of ZNF263 on CRC cells. Additionally, our study found that overexpression of ZNF263 enhanced the resistance of CRC cells to the chemoradiotherapy. In summary, this study not only elucidated the significant role of ZNF263 in CRC but also proposed novel approaches and methodologies for the diagnosis and treatment of this malignancy.
(© 2024. The Author(s).)

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21JR7RA598 Gansu Natural Science Foundation; 21JR1RA016 Gansu Natural Science Foundation; 21JR7RA645 Gansu Youth Natural Science Foundation; 82160588 National Natural Science Foundation of China

Keywords: Chemotherapy; Colorectal cancer; Epithelial-mesenchymal transition; Radiotherapy; Signal transducer and activator of transcription 3; Zinc finger protein 263

0 (STAT3 protein, human)
0 (STAT3 Transcription Factor)
0 (ZNF263 protein, human)
0 (DNA-Binding Proteins)

Date Created: 20240918 Date Completed: 20240918 Latest Revision: 20240921

20240922

PMC11410824

10.1038/s41598-024-72636-0

39294234