Ubiquitin C‑terminal hydrolase‑L1 (UCH‑L1), a member of the lesser‑known deubiquitinating enzyme family, has deubiquitinase and ubiquitin (Ub) ligase activity and the role of stabilizing Ub. UCH‑L1 was first discovered in the brain and is associated with regulating cell differentiation, proliferation, transcriptional regulation and numerous other biological processes. UCH‑L1 is predominantly expressed in the brain and serves a role in tumor promotion or inhibition. There is still controversy about the effect of UCH‑L1 dysregulation in cancer and its mechanisms are unknown. Extensive research to investigate the mechanism of UCH‑L1 in different types of cancer is key for the future treatment of UCH‑L1‑associated cancer. The present review details the molecular structure and function of UCH‑L1. The role of UCH‑L1 in different types of cancer is also summarized and how novel treatment targets provide a theoretical foundation in cancer research is discussed.
The Hippo pathway regulates cancer biology in many aspects and the crosstalk with other pathways complicates its role. Accumulated evidence has shown that the bidirectional interactions between tumor cells and tumor microenvironment (TME) are the premises of tumor occurrence, development, and metastasis. The relationship among different components of the TME constitutes a three-dimensional network. We point out the core position of the Hippo pathway in this network and discuss how the regulatory inputs cause the chain reaction of the network. We also discuss the important role of Hippo-TME involvement in cancer treatment.
Background: Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of neuromuscular transmission. The objective was to examine the efficacy and safety of 3,4-diaminopyridine (3,4-DAP) in patients with LEMS. Methods: We searched several databases to identify relevant studies, including PubMed, EMBASE, Web of Science, MEDLINE, Cochrane Neuromuscular Disease Group Specialized Register and the Cochrane Central Register of Controlled Trials(CENTRAL). The primary outcome, quantitative myasthenia gravis (QMG) score and the secondary outcome, compound muscle action potentials (CMAP) amplitude were pooled by meta-analysis. Results: Six randomised controlled trials (RCTs) involving 115 patients with LEMS were included. QMG score showed a significant decrease (improvement) of 2.76 points (95 % CI, -4.08 to -1.45, p < 0.001) after treatment with 3, 4-DAP. Moreover, the overall mean CMAP amplitude improved significantly in LEMS patients with 3, 4-DAP treatment, compared with placebo treatment (mean difference 1.34 mV, 95 % CI, 0.98 to 1.70, p < 0.001). The overall assessment of all included trials showed a low risk of bias and low heterogeneity. Conclusions: The pooled results of RCTs demonsrated with moderate to high evidence that 3,4-DAP has a significant effect on LEMS treatment, with improvements in muscle strength score and CMAP amplitude.