Search

Background: N6-methyladenosine (m6A) is dysregulated in various cancers, including colorectal cancer (CRC). Herein, we assess the diagnostic potential of peripheral blood (PB) m6A levels in CRC. Methods: We collected PB from healthy controls (HCs) and patients with CRC, analyzed PB RNA m6A levels and the expression of m6A-related demethylase genes FTO and ALKBH5, cocultured CRC cells with PB mononuclear cells (PBMCs), and constructed an MC38 cancer model. Results: PB RNA m6A levels were higher in the CRC than that in HCs. The area under the curve (AUC) of m6A levels (0.886) in the CRC was significantly larger compared with carbohydrate antigen 199 (CA199; 0.666) and carcinoembryonic antigen (CEA; 0.834). The combination of CEA and CA199 with PB RNA m6A led to an increase in the AUC (0.935). Compared with HCs, the expression of FTO and ALKBH5 was decreased in the CRC. After coculturing with CRC cells, the PBMCs RNA m6A were significantly increased, whereas the expression of FTO and ALKBH5 decreased. Furthermore, m6A RNA levels in the PB of MC38 cancer models were upregulated, whereas the expression of FTO and ALKBH5 decreased. Conclusions: PB RNA m6A levels are a potential diagnostic biomarker for patients with CRC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Several molecules are highly expressed in the serum of cancer patients, and can be used as serological markers. This approach has become one of the important auxiliary diagnostic methods for cancer. AIM: To investigate the correlation between the serum levels of EphA2 and VEGF-A and the pathogenesis of colorectal cancer (CRC) as well as the potential value of these molecules in the diagnosis of CRC. METHODS: ELISA was used to detect the levels of EphA2 and VEGF-A in the peripheral venous serum of 106 newly diagnosed patients with CRC and 69 normal controls. The relationship between the serum EphA2 and VEGF-A levels and the clinicopathological characteristics of CRC patients was analyzed. ROC analysis was used to investigate the diagnostic value of the serum EphA2 and VEGF-A levels in CRC, and the optimal cutoff value was calculated. RESULTS: The serum levels of EphA2 and VEGF-A in the CRC group were higher than those in the control as well as CEA, the serum level of EphA2 was positively correlated with the VEGF-A levels, but neither was significantly associated with the clinicopathological parameters of CRC. The ROC curve showed that the single index AUC was < 0.7 except for VEGF-A, and the accuracy of the combined diagnosis was higher than that of any other single index. The diagnosis scheme involving all three markers was the best (the sensitivity was 60.40%, the specificity was 92.8%, and the accuracy was 53.1%). The best critical values calculated were EphA2 > 297.92 ng/ml, EphA2 > 183.92 pg/ml and CEA > 5.19 ng/ml. CONCLUSION: The serum levels of EphA2 and VEGF-A are high in CRC patients, and the combine detection of CEA, EphA2 and VEGF-A can significantly improve the diagnostic accuracy of CRC. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "N6-methyladenosine levels in peripheral blood RNA: a potential diagnostic biomarker for colorectal cancer" published in the journal Cancer Cell International. The correction states that the order of the corresponding author in the author list was incorrect and should be corrected. Prof. Yingping Cao should be listed as the last author, while Chunying Zhang and Jiadi Chen should be listed as co-first authors. The original article has been corrected. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. [Extracted from the article]

Omentin-1, a 34-kDa protein, has been demonstrated to be associated with colorectal cancer (CRC). Epidemiological and clinical studies have indicated that the levels of circulating omentin-1 are significantly increased in patients with CRC, but the cause of the high omentin-1 levels and whether CRC cells express this adipokine have not been determined. In the present study, human colorectal carcinoma and para-carcinoma tissues were collected from 24 patients with CRC. In addition, SW480 and HCT116 colon cancer cells were cultured in vitro. The expression and localization of omentin-1 protein in human CRC and para-carcinoma tissues were determined by immunohistochemistry. The mRNA and protein expression levels of omentin-1 in human CRC and para-carcinoma tissues were detected by reverse transcription-quantitative PCR (RT-qPCR) and western blotting, respectively. In addition, omentin-1 mRNA expression levels in SW480 and HCT116 cell lines were detected by RT-qPCR. Since SW480 cells exhibited higher omentin-1 mRNA levels compared with those of HCT116 cells, SW480 cells were selected for further experiments. The expression of omentin-1 protein in the supernatant and lysate of SW480 cells obtained at 6, 12, 24 and 48 h was determined by ELISA. The immunohistochemistry results demonstrated that the positive expression of omentin-1 protein was mainly located in the cytoplasm of cancer cells in human CRC tissues. The mRNA and protein expression levels of omentin-1 in the CRC tissues were higher compared with those in para-carcinoma tissues. The expression levels of omentin-1 were detected in the cell lysate and supernatant of SW480 cells; the expression level of omentin-1 protein in the cell lysate was higher compared with that in the supernatant. These results indicated that SW480 cells secret and express the adipokine omentin-1 endogenously. Omentin-1 may serve its potential carcinogenetic role in CRC through endocrine, autocrine and paracrine pathways. [ABSTRACT FROM AUTHOR]

Evodiamine (Evo) is an alkaloid that can be extracted from the berry fruit Evodia rutaecarpa and has been reported to exert various pharmacological effects, such as antidiarrheal, antiemetic and antiulcer effects. In vivo, the potential effects of Evo were investigated in a mouse model of dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) and in adenomatous polyposis coli (Apc)MinC/Gpt C57BL/6 mice with colorectal cancer (CRC), where the latter harbours a point-mutation in the Apc gene. Evo suppressed the degree of weight loss and colon shortening induced by DSS, decreased the disease activity index value and ameliorated the pathological alterations in the colon of mice with UC as examined via H&E staining of colon tissues. In addition, Evo decreased the number and size of colonic tumors in ApcMinC/Gpt mice. Proteomics (colon tissues), ELISA (colon tissues and serum) and western blotting (colon tissues) results revealed that Evo inhibited NF-κB to mediate the levels of various cytokines, including, in the DSS-induced UC model, IL-1β, IL-2, IL-6, IL-8, TNF-α, IFN-γ (ELISA of colon tissues and serum), NF-κB, IKKα+β, IκBα, S100a9, TLR4 and MyD88 (western blotting of colon tissues), and, in the colorectal cancer model, IL-1β, IL-2, IL-6, IL-15, IL-17, IL-22, TNF-α (ELISA of colon tissues and serum), NF-κB, IKKα+β, IκBα and S100a9 (western blotting of colon tissues), to achieve its anti-inflammatory and antitumor effects. In vitro, Evo also reduced the viability of the colon cancer cell line SW480, inhibited mitochondrial membrane potential (MMP detection), caused G2/M-phase arrest (cell cycle detection) and suppressed the translocation of phosphorylated-NF-κB from the cytoplasm into the nucleus (immunofluorescence of p-NF-κB). Theoretical evidence (MD simulations) suggest that Evo may bind to the ordered domain (α-helix) of NF-κB to influence this protein. The protein secondary structure changes were analyzed by the cpptraj module in Amber. In addition, these data provide experimental evidence that Evo may be an effective agent for treating UC and CRC. [ABSTRACT FROM AUTHOR]

Background: In China, the incidence of ulcerative colitis (UC) is increasing every year, but the etiology of UC remains unclear. UC is known to increase the risk of colorectal cancer (CRC). The aim of this study was to investigate the protective effects of crocin against UC and CRC in mouse models. Methods: Crocin was used to treat the dextran sodium sulfate (DSS)-induced UC mice for 3 weeks, and ApcMinC/Gpt mice with colorectal cancer for 8 weeks. Proteomics screening was used to detect changes in the protein profiles of colon tissues of UC mice. Enzyme-linked immunosorbent assays and western blot were used to verify these changes. Results: Crocin strongly reduced the disease activity index scores of UC mice, and improved the pathological symptoms of the colonic epithelium. The anti-inflammatory effects of crocin were indicated by its regulation of the activity of various cytokines, such as interleukins, via the modulation of nuclear factor kappa-B (NF-κB) signaling. Crocin significantly suppressed tumor growth in ApcMinC/Gpt mice and ameliorated pathological alterations in the colon and liver, but had no effects on spleen and kidney. Additionally, crocin significantly decreased the concentrations of interleukins and tumor necrosis factor-α in the sera and colon tissues, suggesting its anti-inflammatory effects related to NF-κB signaling. Finally, 12-h incubation of SW480 cells with crocin caused cell cycle arrest, enhanced the apoptotic rate, promoted the dissipation of mitochondrial membrane potential, and the over-accumulation of reactive oxygen species. From the theoretical analyses, phosphorylated residues on S536 may enhance the protein-protein interactions which may influence the conformational changes in the secondary structure of NF-κB. Conclusion: The protective effects of crocin on UC and CRC were due to its suppression of NF-κB-mediated inflammation. [ABSTRACT FROM AUTHOR]

While previous studies have indicated the involvement of Isthmin 1 (ISM1), a secreted protein, in cancer development, the precise mechanisms have remained elusive. In this study, we unveiled that ISM1 is significantly overexpressed in both the blood and tissue samples of colorectal cancer (CRC) patients, correlating with their poor prognosis. Functional experiments demonstrated that enforced ISM1 expression significantly enhances CRC proliferation, migration, invasion and tumor growth. Notably, our investigation reveals an interaction of ISM1 with epidermal growth factor receptor (EGFR), a member of the receptor tyrosine kinase (RTK) family of CRC cells. The binding of ISM1 triggered EGFR activation and initiate downstream signaling pathways. Meanwhile, intracellular ISM1 interacted with Y-box binding protein 1 (YBX1), enhancing its transcriptional regulation on EGFR. Furthermore, our research uncovered the regulation of ISM1 expression by the hypoxia-inducible transcription factor HIF-1α in CRC cells. Mechanistically, we identified HIF-1α as a direct regulator of ISM1, binding to a hypoxia response element on its promoter. This novel mechanism illuminated potential therapeutic targets, offering insights into restraining HIF-1α/ISM1/EGFR-driven CRC progression and metastasis. • ISM1 promotes the progress of colorectal cancer. • ISM1 interacts directly with EGFR, thereby enhancing the activity of EGFR signaling. • ISM1 upregulates EGFR expression by inhibiting its degradation and transcriptional regulation through interaction with YBX1. • ISM1 is transcriptionally regulated by HIF-1α. [ABSTRACT FROM AUTHOR]