Various miRNAs play critical roles in the development and progression of solid tumors. In this study, we describe the role of miR-204-5p in limiting growth and progression of breast cancer. In breast cancer tissues, miR-204-5p was significantly downregulated compared with normal breast tissues, and its expression levels were associated with increased survival outcome in patients with breast cancer. Overexpression of miR-204-5p inhibited viability, proliferation, and migration capacity in human and murine breast cancer cells. In addition, miR-204-5p overexpression resulted in a significant alteration in metabolic properties of cancer cells and suppression of tumor growth and metastasis in mouse breast cancer models. The association between miR-204-5p expression and clinical outcomes of patients with breast cancer showed a nonlinear pattern that was reproduced in experimental assays of cancer cell behavior and metastatic capacities. Transcriptome and proteomic analysis revealed that various cancer-related pathways including PI3K/Akt and tumor-immune interactions were significantly associated with miR-204-5p expression. PIK3CB, a major regulator of PI3K/ Akt pathway, was a direct target for miR-204-5p, and the association between PIK3CB-related PI3K/Akt signaling and miR-204-5p was most evident in the basal subtype. The sensitivity of breast cancer cells to various anticancer drugs including PIK3CB inhibitors was significantly affected by miR-204-5p expression. In addition, miR-204-5p regulated expression of key cytokines in tumor cells and reprogrammed the immune microenvironment by shifting myeloid and lymphocyte populations. These data demonstrate both cellautonomous and non-cell-autonomous impacts of tumor suppressor miR-204-5p in breast cancer progression and metastasis.Significance: This study demonstrates that regulation of PI3K/Akt signaling by miR-204-5p suppresses tumor metastasis and immune cell reprogramming in breast cancer.

BackgroundRice straw has considerable potential as a raw material for bioethanol production. Popping pretreatment of rice straw prior to downstream enzymatic hydrolysis and fermentation was found to increase cellulose to glucose conversion efficiency. The aim of this study was to investigate the influence of popping pretreatment and determine the optimal enzyme loading using a surface response design.ResultsThe optimal doses of cellulase and xylanase enzymes were 23 FPU and 62 IU/g biomass, respectively. Using the optimized enzyme condition and popping pretreatment of rice straw (15% substrate loading, w/v), a sugar recovery of 0.567 g/g biomass (glucose; 0.394 g/g) was obtained in 48 h, which was significantly higher than that from untreated rice straw (total sugar recovery; 0.270 g/g biomass). Fermentation of the hydrolyzates by Saccharomyces cerevisiae resulted in 0.172 g ethanol/g biomass after 24 h, equivalent to 80.9% of the maximum theoretical yield (based on the amount of glucose in raw material). Changes in the chemical composition and surface area of rice straw were also investigated before and after popping pretreatment. The results showed little or no difference in chemical composition between the pretreated rice straw and the control. However, the surface area of pretreated rice straw increased twofold compared to the control.ConclusionPopping pretreatment of rice straw can effectively improve downstream saccharification and fermentation, important for bioethanol production.

This study provides high-quality variation data of diverse radish genotypes. Genome-wide SNP comparison along with RNA-seq analysis identified candidate genes related to domestication that have potential as trait-related markers for genetics and breeding of radish. Radish (Raphanus sativus L.) is an annual root vegetable crop that also encompasses diverse wild species. Radish has a long history of domestication, but the origins and selective sweep of cultivated radishes remain controversial. Here, we present comprehensive whole-genome resequencing analysis of radish to explore genomic variation between the radish genotypes and to identify genetic bottlenecks due to domestication in Asian cultivars. High-depth resequencing and multi-sample genotyping analysis of ten cultivated and seven wild accessions obtained 4.0 million high-quality homozygous single-nucleotide polymorphisms (SNPs)/insertions or deletions. Variation analysis revealed that Asian cultivated radish types are closely related to wild Asian accessions, but are distinct from European/American cultivated radishes, supporting the notion that Asian cultivars were domesticated from wild Asian genotypes. SNP comparison between Asian genotypes identified 153 candidate domestication regions (CDRs) containing 512 genes. Network analysis of the genes in CDRs functioning in plant signaling pathways and biochemical processes identified group of genes related to root architecture, cell wall, sugar metabolism, and glucosinolate biosynthesis. Expression profiling of the genes during root development suggested that domestication-related selective advantages included a main taproot with few branched lateral roots, reduced cell wall rigidity and favorable taste. Overall, this study provides evolutionary insights into domestication-related genetic selection in radish as well as identification of gene candidates with the potential to act as trait-related markers for background selection of elite lines in molecular breeding.