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PURPOSE: Studies have shown that the gut microbiota may affect anti-tumor immunity by regulating the host immune system and tumor microenvironment. To date, little is known about whether the gut microbiota underlies the occurrence of diffuse large B-cell lymphoma (DLBCL) and drug resistance. METHODS: In the present study, we compared the gut microbiota structure of fecal samples from 26 patients with primary DLBCL, 28 patients with relapsed and refractory (RR) DLBCL, and 30 healthy people. RESULTS: Notably, Fusobacteria (from phylum to species) was enriched in the primary group. A decrease of Fusobacterium and an increase of Enterococcus were found in the RR group. PICRUSt analysis found that genes related to cytochrome P450 were upregulated in the RR group compared to the primary group, which likely contributes to the occurrence of DLBCL and the formation of drug resistance. CONCLUSIONS: Our study provides further evidence for the relationship between gut microbiota and DLBCL and the formation of drug resistance, highlighting the potential significance of the bacterial variations may be used as new biomarkers of DLBCL.
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INTRODUCTION: GEO- and TCGA-based data analysis suggested the differential expression of miR-29c in pancreatic cancer. However, limited data are available on the downstream mechanistic actions of miR-29c, which may fuel the in vitro and in vivo studies of pancreatic cancer. METHODS: The downstream target gene of miR-29c and the downstream ERK/MAPK pathway involved in pancreatic cancer were predicted by bioinformatics tools. Next, the expression of miR-29c and MAPK1 was determined in pancreatic cancer tissues and cells. After ectopic expression and depletion experiments in pancreatic cancer cells, oncogenic phenotypes of pancreatic cancer cells were tested by MTS assay, Transwell assay, and flow cytometry. Effects of miR-29c/MAPK1 on tumorigenic ability in vivo were evaluated in pancreatic cancer xenografts in nude mice. RESULTS: Through differential analysis, five pancreatic cancer-related miRNAs (hsa-miR-29c, hsa-miR-107, hsa-miR-324-3p, hsa-miR-375, and hsa-miR-210) were screened out, among which miR-29c was selected as the key miRNA related to prognosis of pancreatic cancer patients. miR-29c could target and inhibit MAPK1 to suppress the activation of ERK/MAPK pathway. miR-29c was downregulated in pancreatic cancer, and its high expression was related to the good prognosis of pancreatic cancer patients. Both in vitro and in vivo experiments demonstrated that restoration of miR-29c inhibited oncogenic phenotypes of pancreatic cancer cells, as well as repressed tumorigenic ability of pancreatic cancer cells in nude mice. CONCLUSIONS: Taken together, we unveil a novel miR-29c/MAPK1/ERK/MAPK axis that suppresses pancreatic cancer both in vitro and in vivo.