Background Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) metastasis and chemoresistance have not been fully characterized. Methods CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1. Results CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/β-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients. Conclusions CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC. Electronic supplementary material The online version of this article (10.1186/s12943-019-1019-x) contains supplementary material, which is available to authorized users.

BackgroundOral mucositis is probably the most debilitating complication that can arise in treating a patient with head and neck cancer. Little is known about the impacts of oral microbiota on the initiation and progression of mucositis.MethodsBased on 16S rRNA gene sequencing, dynamic changes in oral bacterial profile as well as correlations between the severity of mucositis and bacterial shifts during radiotherapy were investigated.FindingsOur results revealed that bacterial community structure altered progressively during radiation therapy, in parallel with a marked increase in the relative abundance of some Gram-negative bacteria. Patients who eventually developed severe mucositis harbored a significantly lower bacterial alpha diversity and higher abundance of Actinobacillus during the phase of erythema – patchy mucositis. Accordingly, a random forest model for predicting exacerbation of mucositis was generated, which achieved a high predictive accuracy (AUC) of 0.89.InterpretationOral microbiota changes correlate with the progression and aggravation of radiotherapy-induced mucositis in patients with nasopharyngeal carcinoma. Microbiota-based strategies can be used for the early prediction and prevention of the incidence of severe mucositis during radiotherapy.

BackgroundThe metastasis-associated gene 1 (MTA1) has been identified as one critical regulator of tumor metastasis. Previously, we identified miR-125b as a downregualted miRNA in non-small cell lung cancer (NSCLC) cell line upon MTA1 depletion. However, the role of miR-125b and MTA1 in the regulation of NSCLC metastasis remains unclear.MethodsStable MTA1 knockdown NSCLC cell lines 95D and SPC-A-1 were established by transfection with MTA1 shRNA. The effects of MTA1 depletion on the expression of miR-125b and cell migration and invasion were examined by real-time PCR, wound healing and matrigel invasion assay.ResultsMTA1 knockdown led to the upregulation of miR-125b level in NSCLC cells. Furthermore, MTA1 knockdown reduced while miR-125b inhibitor enhanced cell migration and invasion of NSCLC cells. Notably, miR-125b inhibitor antagonized MTA1 siRNA induced inhibition of cell migration and invasion.ConclusionMTA1 and miR-125b have antagonistic effects on the migration and invasion of NSCLC cells. The newly identified MTA1-miR-125b axis will help further elucidate the molecular mechanism of NSCLC progression and suggest that ectopic expression of miR-125b is a potentially new therapeutic regimen against NSCLC metastasis.