Dataset Information

Deubiquitinase DUB3 Regulates Cell Cycle Progression via Stabilizing Cyclin A for Proliferation of Non-Small Cell Lung Cancer Cells.

ABSTRACT: The deubiquitinase DUB3 is frequently overexpressed in non-small cell lung cancer (NSCLC) and contributes to its malignant phenotype. However, the underlying molecular mechanism of DUB3 in NSCLC is largely unknown. In this study, we report that DUB3 regulates cell cycle progression by deubiquitinating cyclin A that links to proliferation of NSCLC cells. We found that knockdown of DUB3 decreases cyclin A levels, whereas overexpression of DUB3 strongly increases cyclin A levels. Mechanistically, DUB3 interacts with cyclin A, which removes the polyubiquitin chains conjugated onto cyclin A and stabilizes the cyclin A protein. Furthermore, we demonstrate that DUB3 regulates cell cycle progression by stabilizing cyclin A, because ablation of DUB3 arrests cell cycle from G0/G1 to S phase and the resulting effect can be rescued by introducing cyclin A into NSCLC cells. Functionally, we found that the effect of DUB3 on cyclin A mediates proliferation of NSCLC cells. Moreover, a significant correlation between DUB3 abundance and cyclin A expression levels were also found in NSCLC samples. Taken together, these results reveal that DUB3 functions as a novel cyclin A regulator through maintaining cyclin A stability, and that the DUB3-cyclin A signaling axis plays a critical role in cell cycle progression for proliferation of NSCLC.

SUBMITTER: Hu B

PROVIDER: S-EPMC6523561 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Deubiquitinase DUB3 Regulates Cell Cycle Progression via Stabilizing Cyclin A for Proliferation of Non-Small Cell Lung Cancer Cells.

Hu Bin B Deng Tanggang T Ma Hongchang H Liu Yan Y Feng Peifu P Wei Dong D Ling Neng N Li Ling L Qiu Siyuan S Zhang Lin L Peng Bo B Liu Jing J Ye Mao M

Cells 20190331 4

The deubiquitinase DUB3 is frequently overexpressed in non-small cell lung cancer (NSCLC) and contributes to its malignant phenotype. However, the underlying molecular mechanism of DUB3 in NSCLC is largely unknown. In this study, we report that DUB3 regulates cell cycle progression by deubiquitinating cyclin A that links to proliferation of NSCLC cells. We found that knockdown of DUB3 decreases cyclin A levels, whereas overexpression of DUB3 strongly increases cyclin A levels. Mechanistically, D ...[more]

PMID: 30935108

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Project description:Accumulating evidence has indicated that aberrant expression of long non-coding RNAs (lncRNAs) is an important oncogenic factor. The aim of the present study was to investigate the role of LINC01296, an lncRNA that exerts a tumor?promoting function in many cancers, in the regulation of proliferation, metastasis and the cell cycle of osteosarcoma. The expression of LINC01296 in osteosarcoma tissues and adjacent healthy tissues of 30 patients was analyzed by quantitative real?time PCR (qRT?PCR). The relationship between LINC01296 expression and the survival of patients with osteosarcoma was also explored. The expression levels of LINC01296 in osteosarcoma cells and normal cells were compared. LINC01296 knockdown and overexpression were performed in MG63 and HOS8603 osteosarcoma cells by transfecting LINC01296 shRNA and an expression plasmid respectively, followed by investigation of the changes on cell proliferation, migration, apoptosis and cell cycle arrest. Western blotting was used to analyze the changes of cell cycle regulators. Cyclin D1 knockdown and overexpression were carried out to verify the interaction between LINC01296 and cyclin D1. LINC01296 overexpression was demonstrated as a biomarker of osteosarcoma, which was closely correlated with the poor survival of patients with osteosarcoma. A high expression of LINC01296 was observed in osteosarcoma cells, which was closely associated with enhanced proliferation, invasion, and migration of osteosarcoma cells. Cyclin D1 expression was positively correlated with the expression of LINC01296 in osteosarcoma cells. Cyclin D1 knockdown or overexpression played a deterministic role in mediating the effect of LINC01296 on osteosarcoma cells. LINC01296 is an oncogenic lncRNA in osteosarcoma. The proliferation, invasion and migration of osteosarcoma cells could be effectively retarded by inhibition of LINC01296. The cancer?promoting effect of LINC01296 on osteosarcoma was determined by cyclin D1.

Dataset Information

Deubiquitinase DUB3 Regulates Cell Cycle Progression via Stabilizing Cyclin A for Proliferation of Non-Small Cell Lung Cancer Cells.

Publications

Deubiquitinase DUB3 Regulates Cell Cycle Progression via Stabilizing Cyclin A for Proliferation of Non-Small Cell Lung Cancer Cells.

Similar Datasets

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