Identification of the Immune-related lncRNA SNHG14/ miR-200a-3p/ PCOLCE2 Axis in Colorectal Cancer.

Context: Procollagen C-endopeptidase enhancer 2 (PCOLCE2) is associated with the degradation of the extracellular matrix and collagen-chain trimerization, playing a yet unexplored role in tumor prognosis. Objective: The study intended to characterize PCOLCE2's influence on colorectal cancer (CRC) using expression analysis and to investigate its prognostic potential. Design: The research team performed a genetic analysis using genetic databases, including The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), the Tumor IMmune Estimation Resource (TIMER), and LinkedOmics. Setting: The study took place at Xianyang Central Hospital, Xianyang, Shaanxi Province, China. Outcome Measures: The research team: (1) identified differentially expressed PCOLCE2; (2) determined PCOLCE2 expression in gastrointestinal neoplasm; (3) determined the relationship between PCOLCE2 expression and clinical information; (4) identified the mRNA-miRNA-lncRNA regulatory network; (5) ascertained miRNA expression regulated changes in downstream mRNA levels, that could affecting patients' overall survival (OS) and prognoses; (6) assessed the correlation between PCOLCE2 and immune cells; (7) established the relationship between PCOLCE2 and the immune checkpoint; (8) determined the correlation between PCOLCE2 and tumor purity and immune cell infiltration; (9) determined the relationship between PCOLCE2 expression and clinicopathological features; and (10) identified the pathological changes of PCOLCE2. Results: PCOLCE2 in colorectal adenocarcinoma (COAD) tissues was significantly lower than that in normal tissues (P < .05), correlating with DNA methylation and copy-number variation. Elevated PCOLCE2 levels were associated with poorer overall survival (OS), with P = 4.2e-07, and with advancing clinical stages-II, III, and IV-of the cancer (all P < .05). Furthermore, PCOLCE2 was significantly associated with the MSI phenotype and was an independent element impacting colorectal cancer's prognosis. The correlation analysis revealed positive connections between PCOLCE2 expression and immune checkpoint-linked genes-programmed cell death protein 1 (PDCD1), cytotoxic T-lymphocyte associated protein 4 (CTLA4), and cluster of differentiation 274 (CD274), all while also being negatively correlated with tumor purity (Cor=-0.223, P = 5.59E-06) and positively associated with CD8+ T cells (Cor=0.087, P = 7.87E-02), CD4+T cells (Cor=0.236, P = 1.64E-06), macrophages (Cor=0.362, p=6.06E-14), neutrophils (Cor=0.206, P = 4.28E-05), B(Cor=0.231, P = 2.95E-06). Conclusions: The current study revealed for the first time that a novel regulatory axis-long noncoding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14)/ miR-200a-3p/ PCOLCE2- can act as the oncogenic axis of CRC cells and that clinicians can use it to predict the OS of colon-cancer patients. Additionally, differences in the protein expression of PCOLCE2 between normal and adenocarcinoma-colorectal tissues suggest its potential as a prognostic biomarker for CRC.

Long Non-Coding RNA Signatures Associated with Ferroptosis Predict Prognosis in Colorectal Cancer.

BACKGROUND: Currently, colorectal cancer has become a common gastrointestinal malignancy that usually occurs in the colon and rectum, and ferroptosis plays a vital role in the pathology and progression of colorectal tumors. METHODS: A total of 627 patients (51 normal and 644 tumor samples) from The Cancer Genome Atlas (TCGA)-COAD and TCGA-READ were included in the study. Lasso and Cox's regression was employed to analyze the characteristic lncRNAs in colorectal cancer samples, and a distinctive prognostic model of ferroptosis-related lncRNAs was established. By analyzing the divergence between the high and low-risk groups of ferroptosis-related lncRNAs, 15 characteristic lncRNAs related to the prognosis of colorectal cancer were evaluated. Kaplan-Meier analysis, operation characteristic curve (ROC), nomogram, and gene set enrichment analyses (GSEA) further confirmed the validity of the characteristic prognostic model with ferroptosis-related lncRNAs. RESULTS: Kaplan-Meier analysis confirmed a high-risk group of ferroptosis-related lncRNA interrelated with a poor prognosis in colorectal cancer. AUC estimates of 1 -, 3 -, and 5-year survival rates for ferroptosis-related lncRNA characteristic models were 0.745, 0.767 and 0.789. GSEA analysis showed that immune and malignancy-related pathways were active in the high-risk score group. In addition, differential analyses of immune function, including Checkpoint, cytolytic, HLA, and T cell co-inhibition, differed significantly betwixt low - and high-risk groups.CD160, TNFRSF18, CD27, PDCD1, CD200R1, ADORA2A, TNFRSF14, LAIR1, CD244, CD40, TNFRSF4, CD70, TNFSF14, TNFRSF25, CD276, HHLA2, VTCN1, LAG3, TNFSF18, and other immune checkpoints had different expressions betwixt the high- and low-risk group. CONCLUSION: Fifteen kinds of lncRNAs with different expressions (AP003555.1, AC099850.3, AL031985.3, LINC01857, STPG3-AS1, AL137782.1, AC124067.4, AC012313.5, AC083900.1, AC010973.2, ALMS1-IT1, AC013652.1, AC133540.1, AP006621.2, AC018653.3) were closely associated with poor prognosis of colorectal cancer. These indicators were significantly correlated with the overall survival (OS) rate and could be used as prognostic evaluation criteria.

SELE gene as a characteristic prognostic biomarker of colorectal cancer.

OBJECTIVE: To investigate the expression and clinical value of the E-selectin gene (SELE) in colorectal cancer (CRC). METHODS: Using gene expression profiles and clinicopathological data for patients with CRC from The Cancer Genome Atlas, and tumor and adjacent normal tissues from 31 patients with CRC from Xianyang Central Hospital, we studied the correlation between SELE gene expression and clinical parameters using Kaplan-Meier and Cox proportional hazards regression analyses. RESULTS: Higher expression of SELE was significantly associated with a poorer prognosis and shorter survival in patients with CRC. The median expression level of SELE was significantly higher in CRC tissues compared with healthy adjacent tissue. Cox regression analysis showed that the prognosis of CRC was significantly correlated with the expression of SELE. Immunohistochemical analysis also showed that positive expression of E-selectin increased significantly in line with increasing TNM stage.Conclusion: This study confirmed that SELE gene expression is an independent prognostic factor in patients with CRC.

Daidzein Ameliorates Dextran Sulfate Sodium-Induced Experimental Colitis in Mice by Regulating NF-κB Signaling.

Ulcerative colitis (UC) and Crohn's disease (CD) are collectively referred to as inflammatory bowel diseases (IBDs). The increased pathogenesis of UC leads to a series of complications. We aimed to analyze the anticolitic effect of daidzein (DA) in a dextran sulfate sodium (DSS)-induced colitis mouse model and in activated macrophage RAW264.7 cells. Thirty BALB/c male mice were randomly divided into three groups: control, DSS-treated, and DSS DA (10 mg/kg body weight for seven days). DA supplementation was found to improve the disease activity index, colon length, and spleen weight. Microscopic analysis revealed that DSS-induced mice showed more inflammatory cell infiltration and erosion in the villi. Supplementation of DA reduced these signs significantly. Furthermore, oral administration of DA decreased the level of myeloperoxidase (MPO) and inhibited the expression of p65-NF-κB, p-IκB-α, and p-IKK as well as several inflammatory factors, including TNF-α, IL-1ß, and IL-6, in the colonic tissues. DA also inhibited the production of nitric oxide and prostaglandin E2 in LPS-stimulated RAW 264.7 macrophages. Taken together, these results suggest that DA could inhibit DSS-induced ulcerative colitis and decrease inflammatory factor expression. Thus, DA might be applicable in the treatment of UC.

The E3 ubiquitin ligase RNF146 promotes colorectal cancer by activating the Wnt/ß-catenin pathway via ubiquitination of Axin1.

The E3 ubiquitin ligase ring finger protein 146 (RNF146) has been implicated in tumor development. However, the role and clinical significance of RNF146 in colorectal cancer (CRC) remain unknown. In this study, we reported for the first time that RNF146 was upregulated in CRC tissues as well as in cell lines. Further, RNF146 expression was independent prognostic factor for poor outcome of CRC patients. RNF146 knockdown in cell lines inhibited cell growth, promoted cell apoptosis in vitro and suppressed colorectal tumor growth in vivo. Mechanistic investigations revealed that RNF146 exerted oncogenic role through ubiquitination of Axin1 to activate ß-catenin signaling. In addition, RNF146 expression was positively correlated with ß-catenin expression in CRC tissues. Collectively, our data suggest that RNF146 might function as a oncogene in human CRC, and represent a promising prognostic factor and a valuable therapeutic target for CRC.