IntroductionThe role of CARF, a calcium-responsive transcription factor, in colorectal cancer initiation and development is still unknown. Here, we report that CARF promotes colorectal cancer stemness through ERBB signaling pathway.Materials and methodsBoth colorectal cancer cell lines and primary cells were used in this study. The levels of target mRNA and protein in the cells were examined by qRT-PCR and Western blot. Gene manipulation was achieved by the lentivirus delivery system. Luciferase reporter gene assay was employed to analyze the transcriptional activity of the promoter. ChIP assay was performed for the examination of the binding between CARF and the promoters of MAPK8 and JUN. Kaplan-Meier survival curve was generated by the R2 program. Correlation analysis was performed using Spearman correlation analysis.ResultsAberrant upregulation of CARF has been found in tumor tissues of colorectal cancer patients and associated with poor prognosis. Ectopic expression of CARF promoted the sphere-formation activities, as well as the expression of stem cell markers in colorectal cancer cells and knockdown of CARF, inhibited these activities. The mechanistic analysis showed that CARF directly binds to the promoter of MAPK8 and JUN, promotes the expression of MAPK8 and JUN, activates the ERBB signaling pathway, and thereby promotes the maintenance of the stemness in colorectal cancer cells.ConclusionCARF, as an oncogene, promotes colorectal cancer stemness by activating ERBB signaling pathway. The ERBB signaling pathway that serves as the main downstream effector of CARF could be an efficient drug target for colorectal cancer caused by aberrant expression of CARF.

This study explored the relationship between immunological status and clinical characteristics of aplastic anemia (AA) patients to plasma aluminum levels, which were increased after constant exposure to high levels of this metal. Sixty-two AA patients (33 cases with high and 29 cases with low or no exposure to aluminum) and 30 healthy controls were selected for this study. Aluminum in human albumin solution was measured by inductivity coupled plasma mass spectrometry. IL-10, IL-12, IL-17, and INF-γ levels were measured by enzyme-linked immunosorbent assay. The distribution of lymphocyte subsets were determined by flow cytometry. The expression levels of immunoglobulins and complement C3 and C4 were also measured. Exposure to high aluminum raised the levels of serum aluminum in AA patients (P < 0.01). The levels of hemoglobin and complement C4 were lower in AA patients with high aluminum exposure (P < 0.05 and < 0.01, respectively). The percentage of CD4+ T cells and the ratio of CD4+/ CD8+T cells in peripheral blood in AA patients with high aluminum exposure were higher compared with control AA patients (P < 0.05 in both cases), while the percentage of CD8+ T cells was significantly lower than that in non-aluminum–exposed AA patients (P < 0.05). Compared with non-aluminum–exposed AA patients, the level of IL-10 in the high aluminum–exposed AA group was significantly higher (P < 0.05 in both cases). The immunological and clinical characteristics of AA patients from regions of high aluminum exposure are different to those in from non-aluminum areas. These results suggest that high aluminum exposure alters the immune system in patients suffering from AA.

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