Critical Role of lncEPAT in Coupling Dysregulated EGFR Pathway and Histone H2A Deubiquitination During Glioblastoma Tumorigenesis

Histone 2A (H2A) monoubiquitination is a fundamental epigenetics mechanism of gene expression, which plays a critical role in regulating cell fate. However, it is unknown if H2A ubiquitination is involved in EGFR-driven tumorigenesis. In the current study, we have characterized a previously unidentified oncogenic lncRNA (lncEPAT) that mediates the integration of the dysregulated EGFR pathway with H2A deubiquitination in tumorigenesis. LncEPAT was induced by the EGFR pathway, and high-level lncEPAT expression positively correlated with the glioma grade and predicted poor survival of glioma patients. Mass spectrometry analyses revealed that lncEPAT specifically interacted with deubiquitinase USP16. LncEPAT inhibited USP16\u27s recruitment to chromatin, thereby blocking USP16-mediated H2A deubiquitination and repressing target gene expression, includin

Understanding the roles of N6-methyladenosine writers, readers and erasers in breast cancer

Breast cancer is believed to be driven by epigenetic regulation of genes implicated in cell proliferation, survival, and differentiation. Recently, aberrant N6-methyladenosine (m6A) decorations turned up as crucial epigenetic regulator for malignant breast cancer, which may serve as new targets for breast cancer treatment. Here we briefly outline the functions of m6A and its regulatory proteins, including m6A “writers,” “readers,” and “erasers” on RNA life fate, recapitulate the latest breakthroughs in understanding m6A modification and its regulatory proteins, and the underlying molecular mechanisms that contribute to the carcinogenesis and the progression of breast cancer, so as to provide potential epigenetic targets for diagnosis, treatment and prognosis in breast cancer

Mechanical Properties of Microsteel Fiber Reinforced Concrete and Its Gradient Design in the Partially Reinforced RC Beam

Effects of two kinds of microsteel fibers were employed in reinforced concrete (RC) with different fiber volumes fraction. The RC beam was partially reinforced by microsteel fiber reinforced concrete (MSFRC) based on the idea of gradient design. Flexural performances were specially investigated. Results show that microsteel fiber highly strengthened and toughened the concrete matrix. With the same fiber volume content, the concrete reinforced by Type I fiber was generally better in strength compared with that of Type II, while the bending toughness was substantially improved. The bending strength of the concrete reinforced by microsteel fiber in partial section of tensile region was comparable to that in whole section. Based on the traditional strength theory, the critical MSFRC layer depth of in the partially reinforced RC beam was about 0.3 times of the beam depth, which possessed the same crack resistance ability with the beam composed of MSFRC in the whole section. Compared with that of the reference beam, the cracking load of the partially reinforced beam was enhanced by 119%, and the ratio of the cracking moment to ultimate moment improved by 91%. Moreover, the width and height of the cracks in the partially reinforced beam developed much slower than those in the reference beam, and the steady state in which all cracks emerged appeared later; meanwhile, the crack spacing in the pure bending region was smaller, and the number of cracks in the bending-shear region was less, which means that the partially reinforced beam is of excellent properties to resist cracking and bending. Finally, the calculation formula of the bearing capacity of the partially reinforced beam was proposed, which was in good agreement with experimental results

Mechanical Properties of Microsteel Fiber Reinforced Concrete and Its Gradient Design in the Partially Reinforced RC Beam

Effects of two kinds of microsteel fibers were employed in reinforced concrete (RC) with different fiber volumes fraction. The RC beam was partially reinforced by microsteel fiber reinforced concrete (MSFRC) based on the idea of gradient design. Flexural performances were specially investigated. Results show that microsteel fiber highly strengthened and toughened the concrete matrix. With the same fiber volume content, the concrete reinforced by Type I fiber was generally better in strength compared with that of Type II, while the bending toughness was substantially improved. The bending strength of the concrete reinforced by microsteel fiber in partial section of tensile region was comparable to that in whole section. Based on the traditional strength theory, the critical MSFRC layer depth of in the partially reinforced RC beam was about 0.3 times of the beam depth, which possessed the same crack resistance ability with the beam composed of MSFRC in the whole section. Compared with that of the reference beam, the cracking load of the partially reinforced beam was enhanced by 119%, and the ratio of the cracking moment to ultimate moment improved by 91%. Moreover, the width and height of the cracks in the partially reinforced beam developed much slower than those in the reference beam, and the steady state in which all cracks emerged appeared later; meanwhile, the crack spacing in the pure bending region was smaller, and the number of cracks in the bending-shear region was less, which means that the partially reinforced beam is of excellent properties to resist cracking and bending. Finally, the calculation formula of the bearing capacity of the partially reinforced beam was proposed, which was in good agreement with experimental results.</jats:p