Dataset Information

LPLUNC1 stabilises PHB1 by counteracting TRIM21-mediated ubiquitination to inhibit NF-?B activity in nasopharyngeal carcinoma.

ABSTRACT: Long-palate, lung and nasal epithelium clone 1 (LPLUNC1) is a tumour suppressor gene in nasopharyngeal carcinoma (NPC), and low expression of LPLUNC1 is associated with poor prognosis. Our previous study showed that LPLUNC1 upregulates Prohibitin 1 (PHB1), a pleiotropic protein that functions as a tumour suppressor gene in various cancers. Low expression of PHB1 was also found to be associated with the poor prognosis of NPC patients. However, the mechanisms by which LPLUNC1 upregulates PHB1 and the potential role of PHB1 in NPC are unclear. Here, we found that LPLUNC1 stabilised PHB1 by inhibiting PHB1 ubiquitination, which is mediated by E3 ligase TRIM21. LPLUNC1 competitively impaired the binding of PHB1 to TRIM21 due to its stronger binding affinity to PHB1, suppressing the ubiquitination of PHB1. Therefore, our study indicates that PHB1 acted as a tumour suppressor gene by inhibiting NF-?B activity. Depletion of PHB1 significantly attenuated the anti-tumour effects of LPLUNC1 in NPC cells, and the inhibitory effect of LPLUNC1 on NF-?B activity was thus reversed. Together, our findings revealed a novel mechanism underlying the anticancer effect of LPLUNC1 and clarified that PHB1 may represent a novel, promising candidate tumour suppressor gene in NPC, with potential therapeutic target value.

SUBMITTER: Wang H

PROVIDER: S-EPMC6756001 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

LPLUNC1 stabilises PHB1 by counteracting TRIM21-mediated ubiquitination to inhibit NF-κB activity in nasopharyngeal carcinoma.

Wang Heran H Zhou Yujuan Y Oyang Linda L Han Yaqian Y Xia Longzheng L Lin Jingguan J Tang Yanyan Y Su Min M Tan Shiming S Tian Yutong Y Chen Xiaoyan X Luo Xia X Liang Jiaxin J Rao Shan S Wang Ying Y Xiong Wei W Zeng Zhaoyang Z Wang Hui H Li Guiyuan G Liao Qianjin Q

Oncogene 20190318 25

Long-palate, lung and nasal epithelium clone 1 (LPLUNC1) is a tumour suppressor gene in nasopharyngeal carcinoma (NPC), and low expression of LPLUNC1 is associated with poor prognosis. Our previous study showed that LPLUNC1 upregulates Prohibitin 1 (PHB1), a pleiotropic protein that functions as a tumour suppressor gene in various cancers. Low expression of PHB1 was also found to be associated with the poor prognosis of NPC patients. However, the mechanisms by which LPLUNC1 upregulates PHB1 and ...[more]

PMID: 30886235

Similar Datasets

Project description:BACKGROUND:Malignant behavior and radioresistance, which severely limits the efficacy of radiation therapy (RT) in nasopharyngeal carcinoma (NPC), are associated with tumor progression and poor prognosis. Mesenchymal stem cells (MSCs) are used as a therapeutic tool in a variety of tumors. The aim of this study was to reveal the effect of tumor suppressor microRNA-34c-5p (miR-34c) on NPC development and radioresistance, as well as to confirm that exosomes derived from MSCs overexpressing miR-34c restore the sensitivity to radiotherapy in NPCs. METHODS:Potentially active microRNAs were screened by cell sequencing, Gene Expression Omnibus (GEO) database analysis, and analysis of clinical serum samples from 70 patients. The expression of genes and proteins was detected by Western blotting, quantitative reverse transcription PCR (qRT-PCR), and immunohistochemistry (IHC). Proliferation, apoptosis, invasion, migration and radioresistance of NPC were detected. Luciferase reporter assays were used to verify the interactions of microRNAs with their downstream targets. MSCs exosomes were isolated by ultrafiltration and verified by electron microscopy and nanoparticle tracking technology. RESULTS:The expression of miR-34c was associated with the occurrence and radiation resistance of NPC. In vitro and in vivo experiments indicated that overexpression of miR-34c inhibit malignant behavior such as invasion, migration, proliferation and epithelial-mesenchymal transition (EMT) in NPCs by targeting ?-Catenin. In addition, we found alleviated radioresistance upon miR-34c overexpression or ?-catenin knockdown in NPCs. Exosomes derived from miR-34c-transfected MSCs attenuated NPC invasion, migration, proliferation and EMT. Moreover, miR-34c-overexpressing exosomes drastically increased radiation-induced apoptosis in NPC cells. CONCLUSION:miR-34c is a tumor suppressor miR in NPC, which inhibits malignant behavior as well as radioresistance of tumor. Therefore, exogenous delivery of miR-34c to NPCs via MSC exosomes inhibits tumor progression and increases the efficiency of RT. Combination IR with miR-34c-overexpressing exosomes may be effective treatment for radioresistant NPCs.

Dataset Information

LPLUNC1 stabilises PHB1 by counteracting TRIM21-mediated ubiquitination to inhibit NF-?B activity in nasopharyngeal carcinoma.

Publications

LPLUNC1 stabilises PHB1 by counteracting TRIM21-mediated ubiquitination to inhibit NF-κB activity in nasopharyngeal carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets