SENP2 exerts an anti‑tumor effect on chronic lymphocytic leukemia cells through the inhibition of the Notch and NF‑κB signaling pathways
Autor: | Ting‑Ting Wang, Hui‑Xin Liang, Shi‑Fen Wang, Shun‑Quan Wu, Xiu‑Li Chen, Rong Zhan, Zhen‑Shu Xu, Xue‑Ting Liang, Zong‑Jian Qiu |
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Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Cancer Research Chronic lymphocytic leukemia Cell Notch signaling pathway Apoptosis Biology 03 medical and health sciences 0302 clinical medicine Cell Line Tumor hemic and lymphatic diseases medicine Humans RNA Messenger beta Catenin Aged Aged 80 and over Receptors Notch Oncogene NF-kappa B small ubiquitin related modifier (SUMO)-specific protease 2 Articles Middle Aged β-catenin Cell cycle medicine.disease Leukemia Lymphocytic Chronic B-Cell Gene Expression Regulation Neoplastic Cysteine Endopeptidases Leukemia 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research chronic lymphocytic leukemia Female Signal transduction Signal Transduction Chemotaxis assay |
Zdroj: | International Journal of Oncology |
ISSN: | 1791-2423 1019-6439 |
Popis: | Chronic lymphocytic leukemia (CLL) is one of the most often diagnosed hematological malignant tumors in the Western world and a type of inert B-cell lymphoma that commonly attacks the elderly. Small ubiquitin related modifier (SUMO)-specific protease 2 (SENP2) can act as a suppressor in various types of cancer by regulating the stability of β-catenin to affect the Notch signaling pathway; however, it has a low expression level in CLL cells. In this study, we firstly used western blot analysis and RT-qPCR to detect the protein and mRNA expression levels of SENP2 in the peripheral blood of patients with CLL and healthy volunteers. Secondly, we overexpressed or knocked down the expression of SENP2 in CLL cells and then determined the cell invasive and chemotactic ability in a Transwell assay and chemotaxis assay. We examined the sensitivity of the cells to cytarabine and dexamethasone via a CCK-8 assay and determined the cell apoptotic condition and the expression of the Notch signaling pathway using flow cytometry and western blot analysis. The results demonstrated that the patients with CLL had relatively low expression levels of SENP2. The overexpression of SENP2 in the CLL cells decreased their invasive and proliferative ability, as well as their chemotactic response and enhanced their sensitivity to cytarabine and dexamethasone, while it promoted cell apoptosis. The silencing of SENP2 in the CLL cells generally produced the opposite results. We thus hypothesized that the overexpression of SENP2 downregulated β-catenin expression, thus inhibiting the Notch signaling pathway in CLL cells. Moreover, the nuclear factor (NF)-κB signaling pathway was also regulated by the overexpression of SENP2. On the whole, the findings of this study indicate tha SENP2 can act as a tumor suppressor in CLL cells, and may thus prove to be a novel target for CLL treatment in clinical practice. |
Databáze: | OpenAIRE |
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