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Abstract Radiated tumor cell‐derived extracellular vesicles (RT‐EVs) encapsulate abundant DNA fragments from irradiated tumor cells, in addition to acting as integrators of multiple tumor antigens. Accumulating evidence indicates these DNA fragments from damaged cells are involved in downstream immune responses, but most of them are degraded in cells before incorporation into derived RT‐EVs, thus the low abundance of DNA fragments limits immune responses of RT‐EVs. Here, this study found that different radiations affected fates of DNA fragments in RT‐EVs. Boron neutron capture therapy (BNCT) induced DNA accumulation in RT‐EVs (BEVs) by causing more DNA breaks and DNA oxidation resisting nuclease degradation. This is attributed to the high‐linear energy transfer (LET) properties of alpha particles from the neutron capture reaction of 10B. When being internalized by dendritic cells (DCs), BEVs activated the DNA sensing pathway, resulting in functional enhancements including antigen presentation, migration capacity, and cytokine secretion. After vaccination of the BEVs‐educated DCs (BEV@BMDCs), the effector T cells significantly expanded and infiltrated into tumors, suggesting robust anti‐tumor immune activation. BEV@BMDCs not only effectively inhibited the primary tumor growth and metastasis formation but also elicited long‐term immune memory. In conclusion, a successful DC vaccine is provided as a promising candidate for tumor vaccine.

Abstract Background Though circular RNAs, new non‐coding RNA classes have demonstrated that they have an essential role in the initiation as well as development of CRC (colorectal cancer), whereas in CRC the function and mechanism of hsa_circ_0001666 are less known. Methods Hsa_circ_0001666 was identified by bioinformatics analysis of a circRNA microarray from the GEO database, and its expression in both CRC cell lines and tissues was analysed. A series of in vitro along with in vivo experiments were carried out for exploring the hsa_circ_0001666 functions, including transwell, wound healing, flow cytometry, colony formation, Edu, CCK‐8, soft agar colony formation, tumor xenografts and lung/liver metastasis in mice. RNA pull‐down, RIP (RNA immunoprecipitation), luciferase reporter assay, FISH (fluorescence in situ hybridization) and rescue experiments were used for determining the correlation among hsa_circ_0001666, miR‐576‐5p and PCDH10. Results Hsa_circ_0001666 was downregulated in both CRC cell lines along with tumour tissues. A higher expression level of hsa_circ_0001666 indicated a better clinical prognosis in patients with CRC. Hsa_circ_0001666 knockdown significantly supported CRC cell proliferation along with invasion and inhibited cell apoptosis in vitro. Hsa_circ_0001666 knockdown accelerated the CRC growth and metastasis in vivo. Moreover, the mechanistic study showed that hsa_circ_0001666, acting as ‘ceRNA’ of miR‐576‐5p, prevented PCDH10 downregulation, as well as suppressed EMT and stemness of CRC cells, and the Wnt/β‐catenin signalling pathway. Inhibiting miR‐576‐5p or overexpressing PCDH10 could reverse phenotypic changes caused by knocking down of hsa_circ_0001666. Conclusions Hsa_circ_0001666 suppresses CRC progression through the miR‐576‐5p/PCDH10 axis and may provide a new insight for the diagnosis and treatment of CRC.

Abstract Background The mitogen‐activated protein kinase (MAPK) pathway is highly associated with the progression and metastasis of various solid tumours. MAPK14, a core molecule of the MAPK pathway, plays vital roles in the colorectal cancer (CRC). Recent studies have shown that circRNAs can affect tumour progression by encoding peptides. However, little is known regarding the potential protein translated from circMAPK14 and whether it plays a role in the carcinogenesis of colorectal cancer. Methods The RNA level and translatable potential of circMAPK14 in CRC was verified using qRT‐PCR and public databases. RNase R digestion assay, qRT‐PCR, sanger sequencing and FISH assays were utilised to verify the circular characteristics and subcellular localisation of circMAPK14. The suppressive role of circMAPK14 on the progression and metastasis of CRC was verified in vivo and in vitro. LC/MS analysis combined with western blotting demonstrated the presence and relative expression of circMAPK14‐175aa. The underlying mechanism of circMAPK14‐175aa action to inhibit CRC was identified by co‐IP analysis. The binding of U2AF2 within the flanking introns of circMAPK14 was evaluated by RNA pull‐down assay and RIP assay. Ultimately, luciferase reporter gene assays and ChIP assays confirmed that FOXC1 suppressed transcription of U2AF2 by binding to the U2AF2 promoter in the –400 bp to –100 bp region. Results We identified that hsa_circ_0131663 (termed circMAPK14) showed significantly decreased expression level in cells and tissue samples of CRC, and was primarily localised in the cytoplasm. A series of function experiments demonstrated that circMAPK14 influenced CRC progression and metastasis by encoding a peptide of 175 amino acids (termed circMAPK14‐175aa). We also found that circMAPK14‐175aa reduced nuclear translocation of MAPK14 by competitively binding to MKK6, thus facilitating ubiquitin‐mediated degradation of FOXC1. Moreover, we described a positive feedback loop in CRC in which elevated FOXC1 expression was caused by reduced circMAPK14‐175aa expression. This, in turn, decreased circMAPK14 biogenesis by suppressing U2AF2 transcription. Conclusion In summary, we reported for the first time that circMAPK14 functioned as a tumour‐suppressor by encoding circMAPK14‐175aa, which blocked the progression and metastasis of colorectal cancer.

Abstract Background Long noncoding RNAs (lncRNAs) have emerged as key regulators in multiple cancers, including colorectal cancer (CRC). However, the biological functions and molecular mechanisms underlying most lncRNAs in CRC remain largely unknown. Methods A novel lncRNA (TCONS_00012883) was identified using RNA sequencing. The level of TCONS_00012883 expression in CRC was analyzed by qRT‐PCR. The biological functions of TCONS_00012883 in CRC were investigated by a series of in vitro and in vivo experiments: CCK8, colony formation, EdU, flow cytometric assays, transwell assays, and mouse xenograft. The molecular mechanisms of TCONS_00012883 were demonstrated by RNA pulldown, mass spectrometry analysis, RIP, coimmunoprecipitation, RNA sequencing, chromatin immunoprecipitation, and rescue experiments. Results Elevated expression of TCONS_00012883 was confirmed in CRC and positively associated with a poor prognosis. Functionally, gain‐ and loss‐of‐function assays indicated that TCONS_00012883 promoted proliferation and metastasis of CRC cell lines in vitro and in vivo. Mechanistically, RNA pulldown and mass spectrometry analysis showed that DEAD‐box helicase 3 (DDX3) was the protein partner of TCONS_00012883. Furthermore, RNA sequencing assay revealed that matrix metallopeptidase 1 (MMP1) was the downstream of TCONS_00012883. Intriguingly, we found that transcription factor (YY1) could serve as a bridge between TCONS_00012883, DDX3, and MMP1. Conclusions TCONS_00012883 significantly promoted CRC progression via the DDX3/YY1/MMP1 axis, and thus, may act as a major role in diagnosis and therapy of CRC.

Summary It has been established that gut microbiota influences chicken growth performance and fat metabolism. However, whether gut microbiota affects chicken growth performance by regulating fat metabolism remains unclear. Therefore, seven‐week‐old chickens with high or low body weight were used in the present study. There were significant differences in body weight, breast and leg muscle indices, and cross‐sectional area of muscle cells, suggesting different growth performance. The relative abundance of gut microbiota in the caecal contents at the genus level was compared by 16S rRNA gene sequencing. The results of LEfSe indicated that high body weight chickens contained Microbacterium and Sphingomonas more abundantly (P