<p>CARF, As An Oncogene, Promotes Colorectal Cancer Stemness By Activating ERBB Signaling Pathway</p>

Abstract

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.

Identification of Novel Survival Related lncRNA-miRNA-mRNA Competing Endogenous RNA Network Associated with Immune Infiltration in Colorectal Cancer

“…However, there is currently no study focused on the signi cance of ACOX1 and LITAF in human CRC, so they are worthy of further study. Furthermore, GSEA analysis revealed that all of these key mRNAs were signi cantly enriched in well-known tumorigenesis related pathways, such as JAK-STAT signaling pathway [58], TGF-β signaling pathway [59], ERBB signaling pathway [60], and VEGF signaling pathway [61]. These reports above partially improved the credibility of our research, and further research on the signi cance of the novel ceRNA network in CRC is valuable.…”

The Inhibitory Role of miR-486-5p on CSC Phenotype Has Diagnostic and Prognostic Potential in Colorectal Cancer

“…miR-486-5p promotes the expression of five genes with oncosuppressive role and thereby with a negative effect on the CSC phenotype: FZB [ 56 , 57 ], SMAD4 [ 58 , 59 ], NFATC1 [ 60 , 61 ], CDX2 [ 62 , 63 ] and EP300 [ 64 , 65 ]. On the other hand it inhibits the expression of further five genes with oncogenic and CSC-promoting roles: NRCAM [ 66 , 67 ], JUN [ 68 , 69 ], WNT10A [ 70 , 71 ], FZD8 [ 72 , 73 ], and NODAL [ 74 , 75 ]. Furthermore, miR-486-5p showed a positive effect on the expression of PLK1, involved with a proper cell division process [ 76 ] and with controversial behavior in cancer, in which it is described both as an oncogene [ 77 ] and an oncosuppressor [ 78 ].…”

A microRNA‐clinical prognosis model to predict the overall survival for kidney renal clear cell carcinoma

“…27 Therefore, the adipocytokine signaling pathway and fatty acid metabolism may be involved in KIRC progression. Increasing evidence have shown that the mTOR signaling pathway, 28 PPAR signaling pathway, 29 ErbB signaling pathway, 30 and insulin signaling pathway 31 are significant cancer-related pathways. Moreover, it has been found that DNA replication and P53 signaling pathway, highly correlated with the genesis and development of tumors, were enriched in high-risk group.…”