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Colon adenocarcinoma (COAD) is a highly lethal gastrointestinal malignancy. The five-year survival rate of metastatic colorectal cancer remains low, at 14 percent. Numerous publications have suggested a role for peroxisome proliferator-activated receptors (PPARs) in malignancy. Recent studies have shown that PPARs, as nuclear transcription factors, may serve as potential targets for the treatment of metabolic syndrome tumors and their associated complications. However, the molecular mechanism has not been thoroughly investigated. Hence, in order to enhance the prediction of personalized medicine for PPAR-associated modulators in malignancy treatment, a timely review becomes essential. Utilizing TCGA-COAD expression profile data and patient overall survival (OS) information, this study systematically conducted investigations to identify and develop Hub stem cell-related diagnostic and prognostic identification models, aiming to enhance the multi-gene markers for COAD. Utilizing the differential expression profiles of stem cell-related genes, an 11-gene (SLC27A4, CPT1C, CPT1B, CPT2, CYP4A11, FABP3, FABP7, AQP7, MMP1, ACOX1, ANGPTL4) diagnostic and prognostic model was developed. This model demonstrated precise diagnostic and prognostic capabilities and holds the potential to characterize the clinicopathologic features of COAD. Univariate and multivariate Cox proportional hazards regression analyses were conducted to ascertain the independent factors influencing OS outcomes in COAD. The results revealed that CPT1B, SLC27A4, and FABP3 were identified as independent risk prognostic factors for OS in COAD, whereas ACOX1 and CPT2 served as independent protective prognostic factors. The hub genes associated with PPARs were identified through the differential expression of contrast agent COAD and normal tissues. Finally, the investigation of variations in immune infiltration and the analysis of relevant biological pathways validate the prognostic significance of the independent post-factors within this molecular model. This research aims to provide references for comprehending the mechanism of post-transcriptional regulation of COAD and molecular therapy.

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BACKGROUND: PI4K2A has been found to have a tumor-promoting role in various solid tumors and be involved in various biological procedures. In this article, we aim to investigate the prognostic values of PI4K2A and provide new insights in colon adenocarcinoma (COAD). METHODS: The Cancer Genome Atlas (TCGA) database, Human Protein Atlas online database, and UALCAN database were used to analyze the expression of PI4K2A in COAD and the survival of patients. Univariate and multifactorial Cox regression analyses were used to assess the prognosis of PI4K2A on COAD. GSEA was used to explore PI4K2A-related signaling pathways. In addition, the effect of PI4K2A on immune checkpoint inhibitors (ICIs) treatment was investigated by constructing a TIDE model and predicting the association between PI4K2A and anticancer drug sensitivity through the CellMiner database. RESULTS: In the TCGA database, PI4K2A was highly expressed in COAD and the similar results were verified by qRT-PCR. Survival analysis, utilizing Kaplan-Meier curves, revealed that COAD patients with high PI4K2A expression had a worse prognosis. In addition, PI4K2A expression was discovered to have been associated with T-stage, N-stage, and pathological stage by logistic analysis. Next, we utilized univariate and multifactorial Cox regression analyses to identify PI4K2A as an independent predictor. Additionally, GSEA analysis indicates that PI4K2A is enriched in MAPK signaling pathway, Toll-like receptor signaling pathway, etc. In COAD, PI4K2A was remarkably associated with the tumor immune microenvironment. In addition, by constructing a TIDE model, we discovered that COAD patients in the PI4K2A low-expression cohort were better treated with ICI. Finally, analysis of the CellMiner database predicted that PI4K2A was adversely correlated with the sensitivity of various anticancer drugs. CONCLUSIONS: Our study suggests that PI4K2A may be a potential predictor of poor prognosis in COAD and a potential biomarker for early diagnosis, prognosis, and treatment.

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In-Vehicle Information (IVI) features such as navigation assistance play an important role in the travel of drivers around the world. Frequent use of IVI, however, can easily increase the cognitive load of drivers. The interface design, especially the quantity of icons presented to the driver such as those for navigation, music, and phone calls, has not been fully researched. To determine the optimal number of icons, a systematic evaluation of the IVI Human Machine Interface (HMI) was examined using single-factor and multivariate analytical methods in a driving simulator. When one-way ANOVA was performed, the results showed that the 3-icon design scored best in subjective driver assessment, and the 4-icon design was best in the steering wheel angle. However, when a new method of analyzing the data that enabled a simultaneous accounting of changes observed in the dependent measures, 3 icons had the highest score (that is, revealed the overall best performance). This method is referred to as the fuzzy synthetic evaluation model (FSE). It represents the first use of it in an assessment of the HMI design of IVI. The findings also suggest that FSE will be applicable to various other HMI design problems.

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Long noncoding RNAs (lncRNAs) have vital roles in the progression of colorectal cancer (CRC). Forkhead box P4-antisense RNA 1 (FOXP4-AS1) showed a potential unfavorable prognostic factor for CRC, while its underlying mechanism remains elusive. Thus, the goal of this research is to determine mechanism of FOXP4-AS1 in CRC occurrence and development. Herein, a Dual-luciferase reporter assay was performed to assess the regulation of miR-423-5p to nucleus accumbens-associated protein 1 (NACC1) and activating transcription factor 3 (ATF3) to FOXP4-AS1 promoter. Hematoxylin-eosin (H&E) staining was performed to detect the pathological changes of tumor tissues. Flow cytometry, cell counting kit 8, Transwell, and wound healing assays were conducted to assess apoptosis, proliferation, migration, and invasion of CRC cells, respectively. The results showed that FOXP4-AS1 was highly expressed in CRC cell lines and tissues. CRC progression was promoted by the overexpression of FOXP4-AS1 in HTC116 cells and animal models. Furthermore, FOXP4-AS1 served as a molecular sponge for miR-423-5p, and NACC1 is a direct target of miR-423-5p. MiR-423-5p silencing or overexpression of NACC1 increased proliferation, migration, and invasion of HCT116 cells while suppressing apoptosis. We also found that the upregulation of FOXP4-AS1 was activated by ATF3 in CRC cells. Collectively, our results demonstrated that ATF3-activated FOXP4-AS1 aggravates CRC progression by regulating miR-423-5p/NACC1 axis, indicating a new target for CRC treatment.

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Objective: To explore expression changes and clinical significance of EBI3 in gastric cancer. Methods: Expression of EBI3 in gastric cancer (GC) cell lines, GC tissues, and corresponding adjacent tissues were detected by qRT-PCR, Western blot, or immunohistochemistry. The relationship between the EBI3 expression and clinicopathological features of GC patients was analyzed. Expression of EBI3 in BGC-823 was overexpressed or downregulated, then, the changes of proliferation, migration, invasion, and tumorigenicity of BGC-823 were observed by MTT, scratch test, Transwell test, and tumorigenesis assay model. Results: EBI3 was lowly expressed in GC tissues. EBI3 expression in BGC823 was highest than other cell lines. EBI3 expression was significantly associated with TNM stage. GC patients with low expression of EBI3 had a rather poor prognosis than the GC patients with high expression of EBI3. Low EBI3 expression was an independent risk predictor of the prognosis of GC patients. After EBI3 was overexpressed, the viability, migration, invasion, and tumorigenicity abilities of BGC-823 were significantly reduced. Opposite effect was observed after EBI3 expression was downregulated. Conclusion: EBI3 low expression is closely related to the malignant degree of GC and may be a predictive indicator of the prognosis of GC and potential therapeutic targets.

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Sorafenib (SOR) resistance is still a significant challenge for the effective treatment of hepatocellular carcinoma (HCC). The mechanism of sorafenib resistance remains unclear. Several microRNAs (miRNAs) have been identified as playing a role in impairing the sensitivity of tumor cells to treatment. We examined the mechanism behind the role of miR-92b in mediating sorafenib resistance in HCC cells. We detected that miR-92b expression was significantly upregulated in SOR-resistant HepG2/SOR cells compared to parental HepG2/WT cells. After transfection with miR-92b inhibitor, the proliferation of HepG2/SOR cells was remarkably weakened and rates of apoptosis significantly increased. PTEN was considered to be a functional target of miR-92b according to a luciferase reporter assay. Knockdown of PTEN significantly impaired the ability of miR-92b inhibitor on increasing sorafenib sensitivity of HepG2/SOR cells. Furthermore, we confirmed by western blotting and immunofluorescence that miR-92b can mediate sorafenib resistance by activating the PI3K/AKT/mTOR pathway in HCC cells by directly targeting PTEN. These findings further validate the mechanism of miR-92b in SOR resistance in HCC treatment.

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Sorafenib (SOR) resistance is still a significant challenge for the effective treatment of hepatocellular carcinoma (HCC). The mechanism of sorafenib resistance remains unclear. Several microRNAs (miRNAs) have been identified as playing a role in impairing the sensitivity of tumor cells to treatment. We examined the mechanism behind the role of miR-92b in mediating sorafenib resistance in HCC cells. We detected that miR-92b expression was significantly upregulated in SOR-resistant HepG2/SOR cells compared to parental HepG2/WT cells. After transfection with miR-92b inhibitor, the proliferation of HepG2/SOR cells was remarkably weakened and rates of apoptosis significantly increased. PTEN was considered to be a functional target of miR-92b according to a luciferase reporter assay. Knockdown of PTEN significantly impaired the ability of miR-92b inhibitor on increasing sorafenib sensitivity of HepG2/SOR cells. Furthermore, we confirmed by western blotting and immunofluorescence that miR-92b can mediate sorafenib resistance by activating the PI3K/AKT/mTOR pathway in HCC cells by directly targeting PTEN. These findings further validate the mechanism of miR-92b in SOR resistance in HCC treatment.

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