Circular RNAs in breast cancer diagnosis,treatment and prognosis

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.

Transcriptome analysis reveals therapeutic potential of NAMPT in protecting against abdominal aortic aneurysm in human and mouse

Abdominal Aortic Aneurysm(AAA)is a life-threatening vascular disease characterized by the weakening and ballooning of the abdominal aorta,which has no effective therapeutic approaches due to unclear molecular mechanisms.Using single-cell RNA sequencing,we analyzed the molecular profile of individual cells within control and AAA abdominal aortas.We found cellular heterogeneity,with increased plasmacytoid dendritic cells and reduced endothelial cells and vascular smooth muscle cells(VSMCs)in AAA.Up-regulated genes in AAA were associated with muscle tissue development and apoptosis.Genes controlling VSMCs aberrant switch from contractile to synthetic phenotype were significantly enriched in AAA.Additionally,VSMCs in AAA exhibited cell senescence and impaired oxidative phosphorylation.Similar observations were made in a mouse model of AAA induced by Angiotensin II,further affirming the relevance of our findings to human AAA.The concurrence of gene expression changes between human and mouse highlighted the impairment of oxidative phosphorylation as a potential target for intervention.Nicotinamide phosphoribosyltransferase(NAMPT,also named VISFATIN)signaling emerged as a signature event in AAA.NAMPT was significantly downregulated in AAA.NAMPT-extracellular vesicles(EVs)derived from mesenchymal stem cells restored NAMPT levels,and offered protection against AAA.Furthermore,NAMPT-EVs not only repressed injuries,such as cell senescence and DNA damage,but also rescued impairments of oxidative phosphorylation in both mouse and human AAA models,suggesting NAMPT supplementation as a potential therapeutic approach for AAA treatment.These findings shed light on the cellular heterogeneity and injuries in AAA,and offered promising therapeutic intervention for AAA treatment.

Nanoparticle enhanced combination therapy for stem-like progenitors defined by single-cell transcriptomics in chemotherapy-resistant osteosarcoma

The adaptation of osteosarcoma cells to therapeutic pressure impedes the efficacy of chemotherapy for osteosarcoma.However,the characteristics and cellular organization of therapy-resistant cells in osteosarcoma tumors remain elusive.Here,we utilized single-cell transcriptomics to systematically map the cell-type-specific gene expression in a chemotherapy-resistant osteosarcoma tumor.Our data demonstrated the VEGFR2-JMJD3-abundant subsets as quiescent stem-like cells,thereby establishing the hierarchy of therapy-resistant actively cycling progenitor pools(JMJD3-abundant)in osteosarcoma.VEGFR2 inhibitor and JMJD3 inhibitor synergistically impeded osteosarcoma cell propagation and tumor growth.Although osteosarcoma cells are predisposed to apoptosis induced by the synergistic therapy through activation of the CHOP pro-apoptotic factor via the endoplasmic reticulum(ER)stress,the stem-like/progenitor cells exhibit an adaptive response,leading to their survival.Reduction in cellular glutathione levels in stem-like/progenitor cells caused by the treatment with a glutathione synthesis inhibitor increases ER stress-induced apoptosis.Importantly,the marked therapeutic improvement of synergistic therapy against stem-like/progenitor cells was achieved by using glutathione-scavenging nanoparticles,which can load and release the drug pair effectively.Overall,our study provides a framework for understanding glutathione signaling as one of the therapeutic vulnerabilities of stem-like/progenitor cells.Broadly,these findings revealed a promising arsenal by encapsulating glutathione-scavenging nanoparticles with co-targeting VEGFR2 and JMJD3 to eradicate chemotherapy-resistant osteosarcoma.

Feasible synthesis of porous h-BN by Mg^(2+)induced lattice dislocations for hydrogen and ammonia storage

Hexagonal boron nitride(h-BN)is a two-dimensional(2D)layered material with a structure similar to graphite and it has potential as a hydrogen and ammonia storage material.However,dense packing in the standard h-BN structure limits its surface area and prevents the B and N from being adsorption sites.In this study,the addition of Mg^(2+)during h-BN synthesis facilitated the growth of lattice dislocations and led to a crosslinked three-dimensional(3D)porous structure.A proposed formation mechanism for porous h-BN was confirmed by several characterization routes,most clearly by high-resolution transmission electron microscopy(HRTEM).Porous Mg/BNs exhibited high H_(2)and NH_(3)uptakes and showed potential for H_(2)and NH_(3)storage.