AC004854.2 as a prognostic biomarker in colorectal cancer (CRC) clinical settings. (IMAGE)
Caption
(A) In situ hybridization staining was performed to evaluate AC004854.2 expression in a paraffin-embedded tissue microarray containing 72 paired CRC and adjacent normal tissue samples from Cohort 2. (B) Quantitative analysis revealed significantly higher AC004854.2 expression in CRC tissues compared with matched normal tissues. (C) The diagnostic performance of AC004854.2 for CRC was assessed using receiver operating characteristic curve analysis, yielding an area under the curve of 0.704. (D) Protein levels of c-MYC, CCND2, and CDK4 were evaluated in the paraffin-embedded tissue microarray from Cohort 1 by immunohistochemical staining. (E) Spearman correlation analysis demonstrated significant positive associations between AC004854.2 expression and its downstream targets. (F) Pairwise correlations within the SOX4-AC004854.2-c-MYC/CCND2/CDK4 regulatory axis were visualized using a chord diagram. (G) Kaplan-Meier survival analysis was conducted on 154 patients from Cohort 1 and Cohort 2, with overall survival stratified according to AC004854.2 expression levels (high vs. low). (H) A forest plot derived from multivariate Cox regression analysis indicates that high AC004854.2 expression is an independent predictor of poor prognosis in patients with CRC. (I) A schematic diagram summarizes the functional role of AC004854.2 in CRC. In normal colonic epithelial cells, PUF60 interacts with FUBP1 at the far-upstream element (FUSE) of the c-MYC promoter, forming a transcriptionally repressive complex that effectively suppresses c-MYC expression. During malignant transformation, the transcription factor SOX4 up-regulates the long non-coding RNA AC004854.2, which competitively binds to PUF60 and disrupts its interaction with FUBP1. This dissociation abrogates the repressive function of the complex, leading to the release of c-MYC from transcriptional inhibition and resulting in increased c-MYC transcriptional activity. Consequently, this activation promotes enhanced cell proliferation, invasion, and tumor progression. Statistical analysis: Student's t-test; ∗∗P < 0.01.
Credit
Yanjie Chen, Rui Wang, Dexiang Zhu, Lisha Cheng, Ji Zhao, Xiguo, Li Liang, Tianshu Liu
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