B cells often constitute abundant cellular components in human tumors. Regulatory B cells that are functionally defi ned by their ability to produce IL10 downregulate infl ammation and control T-cell immunity. Here, we identifi ed a protumorigenic subset of B cells that constitutively expressed higher levels of programmed cell death-1 (PD-1) and constituted ∼ 10% of all B cells in advanced-stage hepatocellular carcinoma (HCC).

It is of great importance to identify quantitative trait loci (QTL) controlling fiber quality traits and yield components for future marker-assisted selection (MAS) and candidate gene function identifications. In this study, two kinds of traits in 231 F6:8 recombinant inbred lines (RILs), derived from an intraspecific cross between Xinluzao24, a cultivar with elite fiber quality, and Lumianyan28, a cultivar with wide adaptability and high yield potential, were measured in nine environments. This RIL population was genotyped by 122 SSR and 4729 SNP markers, which were also used to construct the genetic map. The map covered 2477.99 cM of hirsutum genome, with an average marker interval of 0.51 cM between adjacent markers. As a result, a total of 134 QTLs for fiber quality traits and 122 QTLs for yield components were detected, with 2.18–24.45 and 1.68–28.27% proportions of the phenotypic variance explained by each QTL, respectively. Among these QTLs, 57 were detected in at least two environments, named stable QTLs. A total of 209 and 139 quantitative trait nucleotides (QTNs) were associated with fiber quality traits and yield components by four multilocus genome-wide association studies methods, respectively. Among these QTNs, 74 were detected by at least two algorithms or in two environments. The candidate genes harbored by 57 stable QTLs were compared with the ones associated with QTN, and 35 common candidate genes were found. Among these common candidate genes, four were possibly “pleiotropic.” This study provided important information for MAS and candidate gene functional studies.

Background Indoleamine 2,3-dioxygenase 1 (IDO1) is a critical regulator of T cell function, contributing to immune tolerance. Upregulation of IDO1 has been found in many cancer types; however, the regulatory mechanisms and clinical significance of IDO1 in colon cancer are still unclear. Here, we investigated the role of dysregulated microRNA (miRNA) targeting IDO1 in the colon cancer microenvironment. Methods We elucidated IDO1 function by performing cell-based assays and establishing transplanted tumor models in BALB/c mice and BALB/c nude mice. We evaluated IDO1 protein expression by immunohistochemistry (IHC) in a tissue microarray (TMA) and analyzed IDO1 mRNA expression with The Cancer Genome Atlas (TCGA). We screened miRNAs targeting IDO1 by using a dual luciferase reporter assay. We tested the function of microRNA-448 (miR-448) by using western blotting (WB) and fluorescence-activated cell sorting (FACS). Results We demonstrated that stable IDO1 overexpression enhanced xenograft tumor growth in BALB/c mice but not in BALB/c nude mice. We also revealed the involvement of posttranscriptional regulation of IDO1 in colon cancer by observing IDO1 protein levels and mRNA levels. Furthermore, ectopic expression of miRNA mimics suggested that miR-448 could significantly downregulate IDO1 protein expression. Notably, we proved that miR-448 suppressed the apoptosis of CD8 + T cells by suppressing IDO1 enzyme function. Conclusion Our findings indicated that IDO1 suppressed the CD8 + T cell response in colon cancer. miR-448, as a tumor-suppressive miRNA, enhanced the CD8 + T cell response by inhibiting IDO1 expression. The results provide a theoretical basis for the development of new immunotherapy for the treatment of colon cancer. Electronic supplementary material The online version of this article (10.1186/s40425-019-0691-0) contains supplementary material, which is available to authorized users.

Background Acquired resistance remains a limitation of the clinical use of 5-fluorouracil (5-FU). Because exosomes, are important vesicles participating in intercellular communication, their contribution to the development of acquired 5-FU resistance needs to be elucidated. In this study, we aimed to examine the underlying mechanisms of exosomes from 5-FU resistant cells (RKO/R) in sustaining acquired 5-FU resistance in sensitive cells (RKO/P). Methods Exosomes from a 5-FU-resistant cell line (RKO/R) and its parental cell line RKO/P were isolated and co-cultured with 5-FU-sensitive cells. Real-time cellular analysis (RTCA) and FACS analysis were used to examine cell viability and apoptosis. Exosomal protein profiling was performed using shotgun proteomics. Inhibitors and siRNAs were applied to study the involvement of selected proteins in 5-FU resistance. The effect of exosomal p-STAT3 (Tyr705) on the caspase cascade was examined by western blotting (WB) and high content analysis. Xenograft models were established to determine whether exosomal p-STAT3 can induce 5-FU resistance in vivo. Results Our results indicated that exosomes from RKO/R cells significantly promoted cell survival during 5-FU treatment. Proteomics and WB analysis results indicated that GSTP1 and p-STAT3 (Tyr705) were enriched in exosomes from RKO/R cells. Inhibition of p-STAT3 re-sensitized RKO/P cells to 5-FU via caspase cascade. Furthermore, p-STAT3 packaged by exosomes from RKO/R cells increased resistance of tumor cells to 5-FU in vivo. Conclusions Our results reveal a novel mechanism by which p-STAT3-containing exosomes contribute to acquired 5-FU resistance in CRC. This study suggests a new option for potentiating the 5-FU response and finding biomarkers for chemotherapy resistance. Electronic supplementary material The online version of this article (10.1186/s13046-019-1314-9) contains supplementary material, which is available to authorized users.

SummaryCotton is widely cultivated globally because it provides natural fibre for the textile industry and human use. To identify quantitative trait loci (QTLs)/genes associated with fibre quality and yield, a recombinant inbred line (RIL) population was developed in upland cotton. A consensus map covering the whole genome was constructed with three types of markers (8295 markers, 5197.17 centimorgans (cM)). Six fibre yield and quality traits were evaluated in 17 environments, and 983 QTLs were identified, 198 of which were stable and mainly distributed on chromosomes 4, 6, 7, 13, 21 and 25. Thirty‐seven QTL clusters were identified, in which 92.8% of paired traits with significant medium or high positive correlations had the same QTL additive effect directions, and all of the paired traits with significant medium or high negative correlations had opposite additive effect directions. In total, 1297 genes were discovered in the QTL clusters, 414 of which were expressed in two RNA‐Seq data sets. Many genes were discovered, 23 of which were promising candidates. Six important QTL clusters that included both fibre quality and yield traits were identified with opposite additive effect directions, and those on chromosome 13 (qClu‐chr13‐2) could increase fibre quality but reduce yield; this result was validated in a natural population using three markers. These data could provide information about the genetic basis of cotton fibre quality and yield and help cotton breeders to improve fibre quality and yield simultaneously.

Upland cotton (Gossypium hirsutum) is grown for its elite fiber. Understanding differential gene expression patterns during fiber development will help to identify genes associated with fiber quality. In this study, we used two recombinant inbred lines (RILs) differing in fiber quality derived from an intra-hirsutum population to explore expression profiling differences and identify genes associated with high-quality fiber or specific fiber-development stages using RNA sequencing. Overall, 72/27, 1137/1584, 437/393, 1019/184, and 2555/1479 differentially expressed genes were up-/down-regulated in an elite fiber line (L1) relative to a poor-quality fiber line (L2) at 10, 15, 20, 25, and 30 days post-anthesis, respectively. Three-hundred sixty-three differentially expressed genes (DEGs) between two lines were colocalized in fiber strength (FS) quantitative trait loci (QTL). Short Time-series Expression Miner (STEM) analysis discriminated seven expression profiles; gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation were performed to identify difference in function between genes unique to L1 and L2. Co-expression network analysis detected five modules highly associated with specific fiber-development stages, especially for high-quality fiber tissues. The hub genes in each module were identified by weighted gene co-expression network analysis. Hub genes encoding actin 1, Rho GTPase-activating protein with PAK-box, TPX2 protein, bHLH transcription factor, and leucine-rich repeat receptor-like protein kinase were identified. Correlation networks revealed considerable interaction among the hub genes, transcription factors, and other genes.

Circular RNAs (circRNAs) are a newly discovered type of biological molecule that belongs to the noncoding RNA family. Abundant evidence has shown that circRNAs are involved in the progression of various cancers. However, the particular functions of circRNAs in colorectal cancer (CRC) remain elusive. In this study, we investigated the differentially expressed circRNAs in three pairs of cancer tissue and adjacent normal tissue of CRC. We revealed that circGLIS2 expression was higher in CRC tissue and cell lines. Gain-and-loss function assays showed that circGLIS2 was involved in the regulation of cell migration. Moreover, overexpressing circGLIS2 in CRC cells activated the NF-κB pathway and induced pro-inflammatory chemokine production, which evoked tumor-associated inflammation through recruiting leukocytes. In turn, when the cancer cells were exposed to the supernatant of circGLIS2 overexpressed cancer cells, they were endowed with the ability of migration and chemokines production. Furthermore, the rescue assay confirmed that circGLIS2 activated NF-κB signaling and promoted cell migration by sponging miR-671. Overall, our study reveals that circGLIS2, acting as a potential oncogene, maintains the abnormal activation state of the NF-κB signaling pathway via the miR-671 sponge mechanism in CRC cells. This study provides a scientific basis for targeting circGLIS2 in colorectal cancer interventions.

Cotton (Gossypium sp.) is an important worldwide cash crop that provides a competitive renewable natural fiber supply for the demands of textile industry. The development of new textile technologies and the improvement of living standards increase the demands for both fiber quantity and fiber quality. ‘0–153’ is an upland cotton cultivar with excellent fiber quality derived from Asiatic cotton sources, especially with regards to fiber strength. To identify quantitative trait loci (QTLs) for fiber strength in this line, a recombinant inbred line population consisting of 196 lines was developed from a cross between it and ‘sGK9708’. A genetic linkage map consisting of 2393 loci was constructed using this recombinant inbred line population, with single nucleotide polymorphism (SNP) markers from the IntlCottonSNPConsortium_70k chip. Quantitative trait loci for fiber strength were detected across 11 environments using both single‐environment and combined multiple‐environment models. A total of 63 QTLs controlling fiber strength were detected by the single‐environment model. Sixteen QTLs were identified by the combined multiple‐environment model. These QTLs could make a contribution to the improvement of fiber quality via marker‐assisted selection and provide useful information for QTL fine mapping and functional gene research activities as well.