The histone methyltransferase SETD3 plays critical roles in various biological events, and its dysregulation is often associated with human diseases including cancer. However, the underlying regulatory mechanism remains elusive. Here, we reported that ubiquitin-specific peptidase 27 (USP27) promotes tumor cell growth by specifically interacting with SETD3, negatively regulating its ubiquitination, and enhancing its stability. Inhibition of USP27 expression led to the downregulation of SETD3 protein level, the blockade of the cell proliferation and tumorigenesis of hepatocellular carcinoma (HCC) cells. In addition, we found that USP27 and SETD3 expression is positively correlated in HCC tissues. Notably, higher expression of USP27 and SETD3 predicts a worse survival in HCC patients. Collectively, these data elucidated that a USP27-dependent mechanism controls SETD3 protein levels and facilitates its oncogenic role in liver tumorigenesis.
Based on the China Health and Retirement Longitudinal Study (CHARLS) data in 2018, medical assistance and life assistance have significant negative influences on self-rated health, found via an empirical analysis based on the Oprobit model. Such negative influences are robust based on the substitution of explained variables and propensity score matching. It can be found from a heterogeneity analysis that the negative influences of medical assistance on self-rated health are more significant in urban residents and residents in Central China and East China. Meanwhile, negative influences of life assistance on self-rated health are more significant in urban residents, and residents in Central China, East China, and Northeast China. This study provides empirical evidence to improve the health of residents by using medical assistance and life assistance accurately and offers important policy enlightenments to formulate appropriate social assistance policies.
Ubiquitination, a highly versatile process of protein homeostasis, participates in the degradation of the vast majority of cellular proteins. In addition to proteolytic function, ubiquitination can also conduce to modulate cellular processes independent of proteolysis, such as signal transduction, protein trafficking, DNA repair and so on. Apoptosis modulates cell quantity via orderly removing damaged cells effectively and plays a fundamental role in the function of multicellular organisms as well homeostasis, while abnormal regulation of apoptosis can lead to various diseases, especially cancer. Since various tumour cells intrinsically elude apoptotic elimination, emerging strategies targeting induction of apoptosis have become great potential and often necessary cancer therapeutic approaches. Numerous researches have shown that ubiquitination can facilitate or inhibit apoptosis by utilising its proteolytic or non‐proteolytic functions aiming at controlling the levels of key proteins. In this review, we focused on intrinsic apoptosis and summarised how diverse types of ubiquitination regulate intrinsic apoptosis through E3 ligases and deubiquitinating enzymes. Given the mechanisms of ubiquitin‐mediated regulation of intrinsic apoptosis and their physiological relevance, we hope that it will supply more therapeutic strategies for cancer.
Behcet disease (BD) is a form of vasculitis characterized by complex multi-organ manifestations that may frequently recur and induce major tissue damage. Although genetic association studies have identified a number of risk factors, the etiology of BD and its tissue manifestations remains unknown, and the landscape of immune responses in BD is opaque, particularly in terms of inflammatory recurrence. In this study, we mapped the transcriptomes of the immune cell compartment in BD at single-cell resolution, sampling both circulation and affected skin in order to chart the immune interplay driving pathogenesis. Through comprehensive expression and communication analysis of the twenty major cell types identified, we observe striking mechanistic differences in immune response between BD skin lesions and peripheral circulation involving TNF signaling and T cell migration. Through integrated TCR sequencing, we further discover a pattern of clonal sharing between circulating and skin CD8+T cell populations along a trajectory defined by the acquisition of tissue-residential properties. In addition, we also identify a population of expanded CD4+ Tregs with the propensity to produce IL-32. Instead of suppressing effector T cell proliferation and function, IL-32 triggers increased expression of CD97, and may thus encourage prolonged local T cell activity in the skin. Collectively, our data serve to advance understandings of contributions of varying immune cell types to BD pathogenesis in the vasculature and skin, as well as the lifecycle patterns of T cells clones in this context. These data may also assist in further investigations of the mechanisms contributing to Treg dysfunction in systemic autoimmunity, while generating a conceptual model of T cell function contributing to BD recurrence.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.