Down-regulation of DNA key protein-FEN1 inhibits OSCC growth by affecting immunosuppressive phenotypes via IFN-γ/JAK/STAT-1

Oral squamous cell carcinoma(OSCC)escape from the immune system is mediated through several immunosuppressive phenotypes that are critical to the initiation and progression of tumors.As a hallmark of cancer,DNA damage repair is closely related to changes in the immunophenotypes of tumor cells.Although flap endonuclease-1(FEN1),a pivotal DNA-related enzyme is involved in DNA base excision repair to maintain the stability of the cell genome.

Glycolysis reprogramming in cancer-associated fibroblasts promotes the growth of oral cancer through the lncRNA H19/miR-675-5p/PFKFB3 signaling pathway

As an important component of the tumor microenvironment,cancer-associated fibroblasts(CAFs)secrete energy metabolites to supply energy for tumor progression.Abnormal regulation of long noncoding RNAs(lncRNAs)is thought to contribute to glucose metabolism,but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined.In the present study,by using RNA sequencing and bioinformatics analysis,we analyzed the lncRNA/mRNA profiles of normal fibroblasts(NFs)derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma(OSCC).LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs.Using small interfering RNA(siRNA)strategies,we determined that lncRNA H19 knockdown affected proliferation,migration,and glycolysis in oral CAFs.We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway,6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)and miR-675-5p.Furthermore,the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs,as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor.Our study presents a new way to understand glucose metabolism in oral CAFs,theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.

Large electrical strain in lead-free K_(0.5)Na_(0.5)NbO_(3)-based ceramics by heterovalent doping

Heterovalent doped(K_(0.48-0.07)xNa_(0.52-0.43)xBi_(0.5)x)(Nb_(0.95-0.95x)Sb_(0.05-0.05x)Zrx)O_(3)ceramics were fabricated using conventional solid-state reaction.Then,the phase structures,dielectric,ferroelectric,and electricstrain properties were investigated.The compositions were tuned to be located at polymorphic phase boundary with increasing heterovalent Bi3t and Zr4t doping levels.A large strain of 0.19%was obtained at relatively low electric fields of 30 kV/cm in the composition of x=0.04.The normalized large-signal d33*values were approximately 633 pm/V under a low driving electric field of 30 kV/cm,which were comparable or larger than the values reported for other lead-free families.The large strains obtained can be attributed to the formation of nanodomains and high-density domain walls,which were confirmed by the observations of domain morphology using transmission electron microscopy(TEM)technique.Excellent temperature stability of the strain properties of the x=0.04 sample could be ascribed to the sluggish behaviour for the local structural heterogeneity in heterovalent-ion doped KNN ceramic.Theoretical simulations revealed that the Zr^(4t)produce the local stress at the BO6 octahedra and Bi3t could yield off-centering of AO12 ployhedron due to the nature of Bi 6s lone pair electrons,which induced lattice expansion and local distortions in the sample.The local displacements are strongly anisotropic in heterovalent-ion doped system.It is believed that random local fields exist in these compositions owing to the eixstence of charge distribution.Such heterovalent doping of Bi^(3t)and Zr^(4t)could destory simultaneously the orthorhombic symmetry and the short-range ferroelecctric order,leading to the formation of complex nanodomains and local structral hetergenenity.Heterovalent doping may,therefore,offer a new avenve to design novel K0.5Na0.5NbO3(KNN)-based materials for their mutifunctional applications.