Serveur d'exploration sur Pittsburgh

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Regulation of HPV16 E6 and MCL1 by SF3B1 inhibitor in head and neck cancer cells

Identifieur interne : 001694 ( Main/Exploration ); précédent : 001693; suivant : 001695

Regulation of HPV16 E6 and MCL1 by SF3B1 inhibitor in head and neck cancer cells

Auteurs : Yang Gao [États-Unis] ; Sumita Trivedi [États-Unis] ; Robert L. Ferris [États-Unis] ; Kazunori Koide [États-Unis]

Source :

RBID : PMC:4138523

Descripteurs français

English descriptors

Abstract

ABT-737 inhibits the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and BCL-XL. Meayamycin B switches the splicing pattern of myeloid cell leukemia factor 1 (MCL1) pre-mRNA. Specifically, inhibition of splicing factor 3B subunit 1 (SF3B1) with meayamycin B promotes the generation of the proapoptotic, short splicing variant (MCL1-S) and diminishes the antiapoptotic, long variant (MCL1-L). This action was previously associated with the cytotoxicity of meayamycin B in non-small cell lung carcinoma cell lines. ABT-737 induced apoptosis in response to an ablation of MCL1-L by meayamycin B. In this study, we further exploited this synergistic combination in head and neck squamous cell carcinoma (HNSCC), up to 90% of which overexpress MCL1 and BCL-XL. In a panel of seven HNSCC cell lines, the combination of meayamycin B and ABT-737 rapidly triggered a Bax/Bak-mediated apoptosis that overcame the resistance from HPV16-positive HNSCC against each agent alone. Both RT-PCR and Western blotting showed that meayamycin B up-regulated MCL1-S and down-regulated MCL1-L. Significantly, we discovered that SF3B1 was involved in the splicing of oncogenic HPV16 E6 to produce non-oncogenic HPV16 E6*, indicating that SF3B1 may inhibit HPV16-induced tumorigenesis.


Url:
DOI: 10.1038/srep06098
PubMed: 25139387
PubMed Central: 4138523


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

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<term>Phosphoproteins (genetics)</term>
<term>Phosphoproteins (metabolism)</term>
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<term>Caspase 7</term>
<term>Myeloid Cell Leukemia Sequence 1 Protein</term>
<term>Oncogene Proteins, Viral</term>
<term>Phosphoproteins</term>
<term>RNA, Small Interfering</term>
<term>Repressor Proteins</term>
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<term>Protéines de répression</term>
<term>Protéines des oncogènes viraux</term>
<term>Tumeurs de la tête et du cou</term>
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<p>ABT-737 inhibits the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and BCL-X
<sub>L</sub>
. Meayamycin B switches the splicing pattern of myeloid cell leukemia factor 1 (MCL1) pre-mRNA. Specifically, inhibition of splicing factor 3B subunit 1 (SF3B1) with meayamycin B promotes the generation of the proapoptotic, short splicing variant (MCL1-S) and diminishes the antiapoptotic, long variant (MCL1-L). This action was previously associated with the cytotoxicity of meayamycin B in non-small cell lung carcinoma cell lines. ABT-737 induced apoptosis in response to an ablation of MCL1-L by meayamycin B. In this study, we further exploited this synergistic combination in head and neck squamous cell carcinoma (HNSCC), up to 90% of which overexpress MCL1 and BCL-X
<sub>L</sub>
. In a panel of seven HNSCC cell lines, the combination of meayamycin B and ABT-737 rapidly triggered a Bax/Bak-mediated apoptosis that overcame the resistance from HPV16-positive HNSCC against each agent alone. Both RT-PCR and Western blotting showed that meayamycin B up-regulated MCL1-S and down-regulated MCL1-L. Significantly, we discovered that SF3B1 was involved in the splicing of oncogenic HPV16 E6 to produce non-oncogenic HPV16 E6*, indicating that SF3B1 may inhibit HPV16-induced tumorigenesis.</p>
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