Bioinformatic prediction and functional characterization of human KIAA0100 gene

Our previous study demonstrated that human KIAA0100 gene was a novel acute monocytic leukemia-associated antigen (MLAA) gene. But the functional characterization of human KIAA0100 gene has remained unknown to date. Here, firstly, bioinformatic prediction of human KIAA0100 gene was carried out using online softwares; Secondly, Human KIAA0100 gene expression was downregulated by the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system in U937 cells. Cell proliferation and apoptosis were next evaluated in KIAA0100-knockdown U937 cells. The bioinformatic prediction showed that human KIAA0100 gene was located on 17q11.2, and human KIAA0100 protein was located in the secretory pathway. Besides, human KIAA0100 protein contained a signalpeptide, a transmembrane region, three types of secondary structures (alpha helix, extended strand, and random coil) , and four domains from mitochondrial protein 27 (FMP27). The observation on functional characterization of human KIAA0100 gene revealed that its downregulation inhibited cell proliferation, and promoted cell apoptosis in U937 cells. To summarize, these results suggest human KIAA0100 gene possibly comes within mitochondrial genome; moreover, it is a novel anti-apoptotic factor related to carcinogenesis or progression in acute monocytic leukemia, and may be a potential target for immunotherapy against acute monocytic leukemia.

Nanomaterial-based delivery vehicles for therapeutic cancer vaccine development

Nanomaterial-based delivery vehicles such as lipid-based,polymer-based,inorganics-based,and bio-inspired vehicles often carry distinct and attractive advantages in the development of therapeutic cancer vaccines.Based on various delivery vehicles,specifically designed nanomaterials-based vaccines are highly advantageous in boosting therapeutic and prophylactic antitumor immunities.Specifically,therapeutic vaccines featuring unique properties have made major contributions to the enhancement of antigen immunogenicity,encapsulation efficiency,biocompatibility,and stability,as well as promoting antigen cross-presentation and specific CD8^(+)T cell responses.However,for clinical applications,tumor-associated antigen-derived vaccines could be an obstacle,involving immune tolerance and deficiency of tumor specificities,in achieving maximum therapeutic indices.However,when using bioinformatics predictions with emerging innovations of in silico tools,neoantigen-based therapeutic vaccines might become potent personalized vaccines for tumor treatments.In this review,we summarize the development of preclinical therapeutic cancer vaccines and the advancements of nanomaterial-based delivery vehicles for cancer immunotherapies,which provide the basis for a personalized vaccine delivery platform.Moreover,we review the existing challenges and future perspectives of nanomaterial-based personalized vaccines for novel tumor immunotherapies.

Identification of tRNA-derived Fragments and Their Potential Roles in Atherosclerosis

Objective Atherosclerosis(AS),a chronic inflammatory disease,is the basis of cardiovascular disease(CVD).Although the treatment has been greatly improved,AS still imposes a large burden on human health and the medical system,and we still need to further study its pathogenesis.As a novel biomolecule,transfer RNA-derived fragments(tRFs)play a key role in the progression of various disease.However,whether tRFs contribute to atherosclerosis pathogenesis remains unexplored.Methods With deep sequencing technology,the change of tRFs expression profiles in patients with AS compared to healthy control group was identified.The accuracy of the sequencing data was validated using RT qPCR.Subsequently,we predicted the potential target genes of tRFs by online miRNA target prediction algorithms.The potential functions of tRFs were evaluated with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses.Results There were 13 tRFs differentially expressed between patients with AS and healthy controls,of which 2 were up-regulated and 11 were down-regulated.Validation by RT-qPCR analysis confirmed the sequencing results,and tRF-Gly-GCC-009 was highly up-regulated in the AS group based on the results of sequencing which was confirmed by RT-qPCR analysis.Furthermore,GO enrichment and KEGG pathway analyses indicated that 10 signaling pathways were related to tRF-Gly-GCC-009.These pathways might be physiopathological fundamentals of AS,mainly involving in Apelin signaling,Notch signaling and calcium signaling.Conclusion The results of our study provide important novel insight into the underlying pathogenesis and demonstrate that tRFs might be potential biomarkers and therapeutic targets for AS in the future.