BackgroundIncreasing evidence suggests that gut microbiota play a role in the pathogenesis of breast cancer. The composition and functional capacity of gut microbiota associated with breast cancer have not been studied systematically.MethodsWe performed a comprehensive shotgun metagenomic analysis of 18 premenopausal breast cancer patients, 25 premenopausal healthy controls, 44 postmenopausal breast cancer patients, and 46 postmenopausal healthy controls.ResultsMicrobial diversity was higher in breast cancer patients than in controls. Relative species abundance in gut microbiota did not differ significantly between premenopausal breast cancer patients and premenopausal controls. In contrast, relative abundance of 45 species differed significantly between postmenopausal patients and postmenopausal controls: 38 species were enriched in postmenopausal patients, including Escherichia coli, Klebsiella sp_1_1_55, Prevotella amnii, Enterococcus gallinarum, Actinomyces sp. HPA0247, Shewanella putrefaciens, and Erwinia amylovora, and 7 species were less abundant in postmenopausal patients, including Eubacterium eligens and Lactobacillus vaginalis. Acinetobacter radioresistens and Enterococcus gallinarum were positively but weakly associated with expression of high-sensitivity C-reactive protein; Shewanella putrefaciens and Erwinia amylovora were positively but weakly associated with estradiol levels. Actinomyces sp. HPA0247 negatively but weakly correlated with CD3+CD8+ T cell numbers. Further characterization of metagenome functional capacity indicated that the gut metagenomes of postmenopausal breast cancer patients were enriched in genes encoding lipopolysaccharide biosynthesis, iron complex transport system, PTS system, secretion system, and beta-oxidation.ConclusionThe composition and functions of the gut microbial community differ between postmenopausal breast cancer patients and healthy controls. The gut microbiota may regulate or respond to host immunity and metabolic balance. Thus, while cause and effect cannot be determined, there is a reproducible change in the microbiota of treatment-naive patients relative to matched controls.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0515-3) contains supplementary material, which is available to authorized users.

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Background Resistance to drug therapy is a major impediment for successful treatment of patients suffering from breast cancer (BC). Tamoxifen (TAM) is an extensively used therapeutic agent, which substantially reduces the risk of recurrence and associated mortality in BC. This study demonstrated that exosomal transfer of microRNA-9-5p (miR-9-5p) enhanced the resistance of MCF-7 cells to TAM. Methods Initially, BC-related differentially expressed genes (DEGs) and their upstream regulatory miRNAs were identified. The TAM-resistant MCF-7 (MCF-7/TAM) cell line and the non-medicated sensitive MCF-7 cell line were formulated, followed by isolation of the exosomes. Next, the apoptosis rate of exosome-treated MCF-7 cells was determined after co-culture with TAM. The interaction between miR-9-5p and ADIPOQ was identified by a combination of bioinformatic analysis and luciferase activity assay. In order to validate the effect of miR-9-5p and ADIPOQ on TAM resistance in the MCF-7 cells in vitro and in vivo, miR-9-5p was delivered into the exosomes. ADIPOQ and miR-9-5p were identified as the BC-related DEG and upstream regulatory miRNA. Results Exosomes derived from the MCF-7/TAM cells could increase the resistance of MCF-7 cells to TAM. Notably, miR-9-5p altered the sensitivity of BC cells to TAM. In addition, ADIPOQ was negatively regulated by miR-9-5p. Furthermore, MCF-7/TAM cell-derived miR-9-5p inhibited the apoptosis of MCF-7 cells, and promoted the cell resistance to TAM. In vivo experiments in nude mice ascertained that the tumor injected with exosomal miR-9-5p showed improved resistance to TAM. Conclusions Exosomal transfer of miR-9-5p augmented the drug resistance of BC cells to TAM by down-regulating ADIPOQ, suggesting its functionality as a candidate molecular target for the management of BC.

BackgroundGastric cancer remains a major cause of mortality and morbidity worldwide. In recent years, gene-based therapeutic strategies were confirmed promising in cancer inhibition and attracted great attention. RNA interference (RNAi) is a powerful tool for gene therapy and has been widely employed to aid in treatment for various diseases, especially cancers. However, effective delivery of small interfering RNA (siRNA) to target cells in vivo remains a challenge for that it is prone to degradation and only lasts a few days in rapidly dividing cells.MethodsDue to its biocompatibility and well-established safety profile, collagen represents a favourable matrix for in-site drug delivery. In the study, collagen hydrogel was used as carriers to test the feasibility of localized and sustained delivery of Id1-targeted siRNA for in vivo gastric cancer inhibition. To enhance the siRNA delivery, cationic polyethylenimine (PEI) was further emplored for scallold modification. The efficacy of siRNA delivery and cancer inhibition were evaluated with multimodality of mehods in vitro and in vivo.ResultsOur results showed that addition of polyethylenimine (PEI) to collagen can facilitate entry of Id1-siRNA into target cells, prolong the silencing effect, and further inhibit tumor growth both in vitro and in vivo.ConclusionThis collagen-based delivery system may facilitate the pathogenesis elucidation and design of effective therapies against gastric cancer.