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Accumulating evidence has demonstrated that N6-methyladenosine (m6A) plays important roles in various cancers, making it essential to profile m6A modifications at a transcriptome-wide scale in colorectal cancer (CRC). In the present study, we performed high-throughput sequencing to determine the m6A methylome in CRC. We obtained 6 pairs of CRC samples and tumor-adjacent normal tissues from Peking University People’s Hospital. We used MeRIP-seq to determine that compared to the tumor-adjacent normal tissues, the CRC samples had 1343 dysregulated m6A peaks, and 625 m6A peaks were significantly upregulated and 718 m6A peaks were significantly downregulated. Genes with altered m6A peaks play critical roles in regulating glucose metabolism, RNA metabolism and cancer stem cells. Furthermore, we identified 297 hypermethylated m6A peaks and 328 hypomethylated m6A peaks in mRNAs through conjoint analyses of MeRIP-seq and RNA-seq data. After analyzing these genes with differentially methylated m6A peaks and synchronously differential expression, we identified four genes (WDR72, SPTBN2, MORC2 and PARM1) that were associated with prognosis of colorectal cancer patients by searching The Cancer Genome Atlas (TCGA). Our study suggests that m6A modifications play important roles in tumor progression and survival of CRC patients. The results also indicate that modulating m6A modifications may represent an alternative strategy to predict the survival of cancer patients and interfere with tumor progression in the future.

Tumor growth cascade is a complicated and multistep process with numerous obstacles. Until recently, evidences have shown the involvement of microRNAs (miRNAs) in tumorigenesis and tumor progression of various cancers, including colorectal cancer (CRC). In this study, we explored the role of miR-194 and its downstream pathway in CRC. We acquired data through miRNA microarray profiles, showing that the expression of miR-194 was significantly suppressed in CRC tissues compared with corresponding noncancerous tissues. Decreased miR-194 expression was obviously associated with tumor size and tumor differentiation, as well as TNM stage. Both Kaplan–Meier and multivariate survival analysis showed that downregulated miR-194 was associated with overall survival. Moreover, functional assays indicated that overexpression of miR-194 in CRC cell lines inhibited cell proliferation both in vitro and in vivo. In addition, using dual-luciferase reporter gene assay, we found MAP4K4 was the direct target of miR-194. Silencing of MAP4K4 resulted in similar biological behavior changes to that of overexpression of miR-194. We also observed through Human Gene Expression Array that MDM2 was one of the downstream targets of MAP4K4. Knockdown of MAP4K4 downregulated MDM2 expression through transcription factor c-Jun binding to the −1063 to -1057 bp of the promoter. These results suggest that miR-194, regulating the MAP4K4/c-Jun/MDM2 signaling pathway, might act as a tumor suppressor and serve as a novel target for CRC prevention and therapy.

Purpose: According to the 2023 global cancer data, breast cancer is the most common malignant tumor among women in the world. Its occurrence and development is influenced by inflammation, nutrition, and immune status. Therefore, this study combines C-reactive protein (CRP), albumin, and lymphocyte, which can reflect the above states, to form the CRP-albumin-lymphocyte (CALLY) index, an indicator to evaluate its relationship with overall survival (OS) and disease-free survival (DFS) in breast cancer patients. Patients and Methods: We retrospectively analyzed the clinical and follow-up data of 174 patients with breast cancer. The optimal cutoff for the preoperative CALLY index was identified by considering the area under the receiver operating characteristic curve; subsequently, the discriminatory ability of the cutoff was determined. The effect of the CALLY index on overall survival (OS) and disease-free survival (DFS) was analyzed using the Kaplan–Meier method and the Cox proportional hazards model. The CALLY index was calculated as: (Albumin × Lymphocyte)/(CRP × 10⁴). Results: The cut-off value of the CALLY index was determined at 2.285. With a cut-off value of 2.285, patients were divided into two groups: those with CALLY < 2.285 and those with CALLY ≥ 2.285. CALLY Index ≥ 2.285 was associated with better survival outcomes. Multivariate Cox analysis showed that TNM stage and CALLY index were prognostic factors that affected OS and DFS. Conclusion: The CALLY index is a new prognostic biomarker for breast cancer patients after surgery. This new CALLY index allows for suitable patients with a poor prognosis to receive postoperative adjuvant therapy.

Recent studies have indicated the possible function of miR-217 in tumorigenesis. However, the roles of miR-217 in colorectal cancer (CRC) are still largely unknown. We examined the expression of miR-217 and AEG-1 in 50 CRC tissues and the corresponding noncancerous tissues by qRT-PCR. The clinical significance of miR-217 was analyzed. CRC cell lines with miR-217 upregulation and AEG-1 silencing were established and the effects on tumor growth in vitro and in vivo were assessed. Dual-luciferase reporter gene assays were also performed to investigate the interaction between miR-217 and AEG-1. Our data demonstrated that miR-217 was significantly downregulated in 50 pairs of colorectal cancer tissues. MiR-217 expression levels were closely correlated with tumor differentiation. Moreover, decreased miR-217 expression was also associated with shorter overall survival of CRC patients. MiR-217 overexpression significantly inhibited proliferation, colony formation and invasiveness of CRC cells by promoting apoptosis and G0/G1 phase arrest. Interestingly, ectopic miR-217 expression decreased AEG-1 expression and repressed luciferase reporter activity associated with the AEG-1 3′-untranslated region (UTR). AEG-1 silencing resulted in similar biological behavior changes to those associated with miR-217 overexpression. Finally, in a nude mouse xenografted tumor model, miR-217 overexpression significantly suppressed CRC cell growth. Our findings suggest that miR-217 has considerable value as a prognostic marker and potential therapeutic target in CRC.

Downregulation of miR-199b is associated with distant metastasis in colorectal cancer via activation of SIRT1 and inhibition of CREB/KISS1 signaling