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Small nucleolar RNA SNORA67 regulates DLGAP5-activated Wnt pathway to promote colorectal cancer development

ABSTRACT: Background Colorectal cancer is a malignancy with high incidence and mortality rates worldwide, posing a serious threat to human life and health.Since tumor progression is usually hidden onset and most CRCs are diagnosed at a late stage, the exploration of new biomarkers can greatly improve the early diagnosis of CRC and is crucial for treatment and prognosis. Small nucleolar RNA (snoRNA), a conserved short non-coding RNA, involves in the regulation of tumorigenesis and progression. Methods Differentially expressed SNORA67 was screened based on colorectal cancer tissue data from GEO and TCGA databases.Clinical significance of SNORA67 was investigated using Cox proportional risk model, work characteristics（ROC） and survival analysis of subjects. The biological function of SNORA67 was studied by CCK8, plate cloning, Transwell, scratch test, flow cytometry and xenotransplantation of nude mouse models.RNA-seq was designed to clarify the pathway and downstream target genes, and the underlying mechanisms were verified by PCR and WB assay analysis. Results We demonstrated that SNORA67 is highly expressed in colorectal cancer, and was a relevant marker for CRC diagnosis and prognosis. Inhibition of SNORA67 in CRC cell line can inhibit proliferation and migration in vitro, promote apoptosis, affect cell cycle and inhibit tumor growth in vivo.Mechanistically, SNORA67 activates the Wnt signaling pathway in J colorectal cancer by regulating DLGAP5.

ORGANISM(S): Homo sapiens

PROVIDER: GSE273457 | GEO | 2025/09/01

REPOSITORIES: GEO

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Project description:Background: Colorectal cancer (CRC) is an aggressive primary intestinal malignancy with the third-highest incidence and second-highest mortality among all cancer types worldwide. Transcription factors (TFs) regulate cell development and differentiation owing to their ability to recognize specific DNA sequences upstream of genes. Numerous studies have demonstrated a strong correlation between TFs, the etiology of tumors, and therapeutic approaches. Here, we aimed to explore prognosis-related TFs and comprehend their carcinogenic mechanisms, thereby offering novel insights into the diagnosis and management of CRC. Materials and methods: Differentially expressed TFs between CRC and normal tissues were identified leveraging The Cancer Genome Atlas database, Weighted correlation network analysis and Cox regression analysis were performed to identify prognosis-related TFs. The cellular functions of hub TF zinc finger E-box binding homeobox 1 (ZEB1) were determined using by 5-ethynyl-2'-deoxyuridine and cell invasion assays in CRC cells. RNA-sequencing, Kyoto Encyclopedia of Genes and Genomes enrichment, and gene set enrichment analyses were used to identify the cellular processes in which ZEB1 participates. Immunoaffinity purification, silver staining mass spectrometry, and a chromatin immunoprecipitation assay were conducted to search for proteins that might interact with ZEB1 and the target genes they jointly regulate. Results: Thirteen central TFs related to prognosis were identified through bioinformatics analysis techniques. Among these TFs, ZEB1 emerged as the TF most closely associated with CRC, as determined through a combination of regulatory network diagrams, survival curves, and phenotype analyses. ZEB1 promotes CRC cell growth by recruiting the NuRD(MTA1) complex, and the ZEB1/NuRD(MTA1) complex transcriptionally represses glycolysis-associated tumor suppressor genes. Conclusion: Our study not only identified a hub biomarker related to CRC prognosis but also revealed the specific molecular mechanisms through which ZEB1 affects cancer progression. These insights provide crucial evidence for the diagnosis of CRC and potential treatment opportunities.

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Small nucleolar RNA SNORA67 regulates DLGAP5-activated Wnt pathway to promote colorectal cancer development

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