USF2-Mediated Transcription of BZW2 Contributes to CRC Malignant Progression by Affecting LAMP3

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Gene Medicine Pub Date : 2025-03-20 DOI:10.1002/jgm.70016

Xintao Li, Yizhi Liu, Shuang Liu, Nanzheng Chen

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引用次数: 0

Abstract

Background

Colorectal cancer (CRC) is one of the most frequent causes of cancer death in China, and its occurrence, development, and prognosis are closely related to the living state of patients. Basic leucine zipper and W2 domains 2 (BZW2), also known as eIF5-mimin protein 1 (5MP1), is a translational regulatory protein and highly expressed in CRC and promotes malignant progression of CRC, but the specific mechanism has not been clarified.

Methods

The databases were used to mine related genes. The expression levels of genes were detected by quantitative real-time PCR (qRT-PCR) and western blot. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay, 5-ethynyl-2′-deoxyuridine (EdU) staining, flow cytometry, transwell assay, and sphere formation assay were employed to examine the effects of BZW2 on the phenotypes in CRC cells in vitro. The mechanism of BZW2 in CRC progression was determined by chromatin immunoprecipitation (CHIP) and dual luciferase reporter assay. In vivo, xenograft animal model was performed to verify the results.

Results

BZW2 was elevated in CRC tissues and cells and was associated with poor prognosis of patients. Functionally, BZW2 enhanced CRC cell proliferation, invasion, and sphere formation but restrained apoptosis. CHIP and dual luciferase reporter assay confirmed that upstream transcription factor 2 (USF2) regulated BZW2 transcription. Also, BZW2 could attenuate the effects of USF2 defection in CRC progression. Meanwhile, lysosomal associated membrane protein 3 (LAMP3) acted as the target of BZW2 and restored the action of BZW2 knockdown. Similarly, BZW2 was involved in tumorigenesis in vivo by the same mechanism in vitro.

Conclusion

These findings revealed a molecular basis for BZW2's promotion of CRC malignant progression and highlighted the role of BZW2 in promoting cancer stemness.

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.