ABSTRACT
Background Ewings sarcoma is the second most common bone and soft tissue malignancy in children and adolescents. Tumor necrosis factor-α-induced protein 8-like 1 (TIPE1) functions as a tumor suppressor in several cancers. Activation of Wnt/β-catenin signaling in subpopulations of tumor cells contributes to phenotypic heterogeneity and disease progression in Ewings sarcoma. The exact role of TIPE1 in Ewings sarcoma remains to be elucidated. Purpose This study aimed to assess the expression and function of TIPE1 in Ewings sarcoma. Method TIPE1 expression in Ewings sarcoma cells was determined by qPCR and western blotting. Furthermore, the Ewings sarcoma cell line RD-ES was transfected with a lentivirus-based TIPE1 expression system to upregulate the expression of TIPE1. The Cell Counting Kit 8 was used to assess the effect of TIPE1 on cell proliferation. The effects of TIPE1 on cell migration and invasion was detected by Transwell assay. Flow cytometry was performed to detect apoptosis. Results Our results suggested lower TIPE1 expression in Ewings sarcoma cell lines compared with normal osseous cells. TIPE1 remarkably inhibited the growth and proliferation of Ewings sarcoma cell; TIPE1 also induced apoptosis and inhibited invasion in vitro. TIPE1 inhibited Ewings sarcoma growth, motility, and survival through regulation of Wnt/β-catenin signaling. Conclusions Our results demonstrated the anti-tumor function of TIPE1 in Ewings sarcoma and reveal a novel therapeutic target (AU)
Subject(s)
Humans , Child , Adolescent , Bone Neoplasms/drug therapy , Bone Neoplasms/genetics , Sarcoma, Ewing/drug therapy , Sarcoma, Ewing/genetics , Cell Proliferation , Gene Expression Profiling , Signal Transduction , Wnt Proteins/genetics , Wnt Proteins/metabolism , beta Catenin/genetics , beta Catenin/metabolism , ApoptosisABSTRACT
This paper addresses the asynchronous stabilization problem of two typical stochastic switching systems, i.e., dual switching systems and semi-Markov jump systems. By dual switching, it means that the systems contain both deterministic and stochastic switching dynamics. New stability criteria are firstly proposed for these two switched systems, which can well handle the asynchronous phenomenon. The conditional expectation of Lyapunov functions is allowed to increase during some unmatched interval to reduce the conservatism. Next, we present numerically testable asynchronous controller design methods for the dual switching systems. The proposed method is suitable for the situation where the asynchronous modes come from both inaccurate mode detection and time varying delay. Meanwhile, the transition probabilities are both uncertain and partly accessible. Finally, novel asynchronous controller design methods are proposed for the semi-Markov jump systems. The sojourn time of the semi-Markov jump systems can have both lower and upper bounds, which could be more practical than previous scenarios. Examples are utilized to demonstrate the effectiveness of the proposed methods.