Background: It has been shown that miR-144-3p regulates cell proliferation, apoptosis, migration and invasion in various cancers. However, the function and expression of miR-144-3p in colorectal cancer (CRC) remained obscure. Methods: Immunohistochemical (IHC) staining was performed to investigate the protein expression of BCL6 in CRC tissues. The effect of BCL6 and miR-144-3p on CRC cells was explored through methylthiazolyl tetrazolium (MTT) assay, colony formation and cell cycle assays. Luciferase reporter assays, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were carried out to determine that BCL6 is directly regulated by miR-144-3p. Results: Our results showed that miR-144-3p is down-regulated in CRC and correlates with the tumor progression of CRC patients. miR-144-3p inhibits cell proliferation and delays G1/S phase transition of CRC cells. Moreover, we found that BCL6 is a new target of miR-144-3p. Furthermore, BCL6 is a mediator of miR-144-3p repression of cell proliferation and cell cycle arrest in CRC cells. miR-144-3p repression of Wnt/β-catenin signaling is mediated by BCL6 in CRC cells. Conclusions: Overall, the effect of the miR-144-3p/BCL6 axis on regulating CRC carcinogenesis was demonstrated, and miR-144-3p was identified as a potential prognostic and therapeutic target in colorectal cancer.

Objective: The current meta-analysis evaluated the association between vitamin B 12 intake and blood vitamin B 12 level and colorectal cancer (CRC) risk. Design: The PubMed and EMBASE databases were searched. A dose-response analysis was performed with generalized least squares regression, with the relative risk (RR) and 95 % CI as effect values. Setting: The meta-analysis included seventeen studies. Subjects: A total of 10 601 patients. Results: The non-linear dose-response relationship between total vitamin B 12 intake and CRC risk was insignificant (P = 0·690), but the relationship between dietary vitamin B 12 intake and CRC risk was significant (P < 0·001). Every 4·5 μg/d increment in total and dietary vitamin B 12 intake was inversely associated with CRC risk (total intake: RR = 0·963; 95 % CI 0·928, 0·999; dietary intake: RR = 0·914; 95 % CI 0·856, 0·977). The inverse association between vitamin B 12 intake and CRC risk was also significant when vitamin B 12 intake was over a dosage threshold, enhancing the non-linear relationship. The non-linear dose-response relationship between blood vitamin B 12 level and CRC risk was insignificant (P = 0·219). There was an insignificant association between every 150 pmol/l increment in blood vitamin B 12 level and CRC risk (RR = 1·023; 95 % CI 0·881, 1·187). Conclusions: Our meta-analysis indicates that evidence supports the use of vitamin B 12 for cancer prevention, especially among populations with high-dose vitamin B 12 intake, and that the association between CRC risk and total vitamin B 12 intake is stronger than between CRC risk and dietary vitamin B 12 intake only.

Metabolic reprogramming is an emerging hallmark of tumor cells. In order to survive in the nutrient-deprived environment, tumor cells rewire their metabolic phenotype to provide sufficient energy and build biomass to sustain their transformed state and promote malignant behaviors. Amino acids are the main compositions of protein, which provide key intermediate substrates for the activation of signaling pathways. Considering that cells can synthesize arginine via argininosuccinate synthase 1 (ASS1), arginine is regarded as a non-essential amino acid, making arginine depletion as a promising therapeutic strategy for ASS1-silencing tumors. In this review, we summarize the current knowledge of expression pattern of ASS1 and related signaling pathways in cancer and its potential role as a novel therapeutic target in cancer. Besides, we outline how ASS1 affects metabolic regulation and tumor progression and further discuss the role of ASS1 in arginine deprivation therapy. Finally, we review approaches to target ASS1 for cancer therapies.