Current cancer drug targets · 2020
USP48 Sustains Chemoresistance and Metastasis in Ovarian Cancer.
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Lei Xuemeng, Li Xukun, Chen Hongyan, Liu Zhihua
Аннотация
BACKGROUND: Ubiquitin specific protease 48 (USP48) is a member of the deubiquitinating enzymes (DUBs) family. However, the function of USP48 in ovarian cancer remains unclear.
OBJECTIVE: The present study reveals that USP48 knockdown could significantly inhibit cell migration and invasion in ES2, 3AO and A2780 cells, without affecting cell proliferation.
METHODS: After carboplatin (CBP) treatment, the USP48 ablation increases the apoptosis rate, and the cleaved PARP and cleaved caspase 3 expression levels in ES2, 3AO and A2780 cells. The subcutaneous tumor and intraperitoneally injected experiments demonstrated that the USP48 knockdown significantly increases responsiveness to CBP, and alleviates the metastasis in vivo. Meanwhile, USP48 deficiency results in the improved survival of mice.
RESULTS: Finally, the analysis of clinical samples and the TCGA and Kaplan-Meier Plot database revealed that the high expression of USP48 in ovarian cancer patients is associated with poor survival and resistance to CBP therapy.
CONCLUSION: In summary, USP48 may be a potential therapeutic target for ovarian cancer patients.
OBJECTIVE: The present study reveals that USP48 knockdown could significantly inhibit cell migration and invasion in ES2, 3AO and A2780 cells, without affecting cell proliferation.
METHODS: After carboplatin (CBP) treatment, the USP48 ablation increases the apoptosis rate, and the cleaved PARP and cleaved caspase 3 expression levels in ES2, 3AO and A2780 cells. The subcutaneous tumor and intraperitoneally injected experiments demonstrated that the USP48 knockdown significantly increases responsiveness to CBP, and alleviates the metastasis in vivo. Meanwhile, USP48 deficiency results in the improved survival of mice.
RESULTS: Finally, the analysis of clinical samples and the TCGA and Kaplan-Meier Plot database revealed that the high expression of USP48 in ovarian cancer patients is associated with poor survival and resistance to CBP therapy.
CONCLUSION: In summary, USP48 may be a potential therapeutic target for ovarian cancer patients.
Предметные рубрики MeSH
AnimalsAntineoplastic AgentsApoptosisCarboplatinCell Line, TumorCell MovementCell ProliferationDrug Resistance, NeoplasmFemaleGene Knockdown TechniquesHEK293 CellsHumansMiceMice, Inbred BALB CMice, NudeMiddle AgedNeoplasm MetastasisOvarian NeoplasmsProgression-Free SurvivalTransfectionTumor BurdenUbiquitin-Specific ProteasesXenograft Model Antitumor Assays