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The histone methyltransferase SETD8, which methylates the lysine 20 of histone H4 (H4K20), is reportedly involved in human carcinogenesis along with nonhistone proteins such as p53. However, its expression profiles and functions in the context of high-grade serous ovarian carcinoma (HGSOC) are still unknown. The purpose of this study was to investigate the role of SETD8 in HGSOC. We performed quantitative real-time PCR and immunohistochemistry to detect the expression of SETD8 in HGSOC samples and normal ovarian specimens. Then, we assessed the effect of the inhibition of SETD8 expression using small interfering RNA (siRNA) and a selective inhibitor (UNC0379) on cell proliferation and apoptosis in HGSOC cells. The expression of SETD8 was significantly upregulated in clinical ovarian cancer specimens compared to that in the corresponding normal ovary. In addition, suppression of SETD8 expression in HGSOC cells with either siRNA or UNC0379 resulted in reduced levels of H4K20 monomethylation, inhibition of cell proliferation, and induction of apoptosis. Furthermore, UNC0379 showed a long-term antitumor effect against HGSOC cells, as demonstrated by colony-formation assays. SETD8 thus constitutes a promising therapeutic target for HGSOC, warranting further functional studies.

We study the dynamics of Dirac and Weyl electrons in disordered point-node semimetals. The ballistic feature of the transport is demonstrated by simulating the wave-packet dynamics on lattice models. We show that the ballistic transport survives under a considerable strength of disorder up to the semimetal-metal transition point, which indicates the robustness of point-node semimetals against disorder. We also visualize the robustness of the nodal points and linear dispersion under broken translational symmetry. The speed of the wave packets slows down with increasing disorder strength, and vanishes toward the critical strength of disorder, hence becoming the order parameter. The obtained critical behavior of the speed of the wave packets is consistent with that predicted by the scaling conjecture.