Dihydromyricetin induced lncRNA MALAT1-TFEB-dependent autophagic cell death in cutaneous squamous cell carcinoma
Identifieur interne : 000883 ( Main/Exploration ); précédent : 000882; suivant : 000884Dihydromyricetin induced lncRNA MALAT1-TFEB-dependent autophagic cell death in cutaneous squamous cell carcinoma
Auteurs : Miduo Tan [République populaire de Chine] ; Bin Jiang [République populaire de Chine] ; Haihua Wang [République populaire de Chine] ; Wei Ouyang [République populaire de Chine] ; Xiang Chen [République populaire de Chine] ; Taoli Wang [République populaire de Chine] ; Dan Dong [République populaire de Chine] ; Shun Yi [République populaire de Chine] ; Jiansheng Yi [République populaire de Chine] ; Yan Huang [République populaire de Chine] ; Manling Tang [République populaire de Chine] ; Yan Xiao [République populaire de Chine] ; Zuiming Jiang [République populaire de Chine] ; Wei Zhou [République populaire de Chine]Source :
- Journal of Cancer [ 1837-9664 ] ; 2019.
Abstract
Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer. Dihydromyricetin (DHM), a Rattan tea extract, has been shown to have antitumor activity with no obvious toxicity to normal cells in vitro and in vivo. However, its efficacy in the treatment of CSCC and the underlying antitumor mechanism has not been fully elucidated yet. In our study, DHM increased autophagic flux in the A431 cells, as evidenced by the upregulation of LC3-II and downregulation of P62/SQSTM1. Moreover, the pharmacological or genetic blocking autophagy decreased DHM-induced cell death, indicating DHM triggered autophagic cell death in A431 cells. Specifically, DHM induced TFEB(Ser142) de-phosphorylation, activated TFEB nuclear translocation and increased of TFEB reporter activity, which contributed to the expression of autophagy-related genes and subsequent initiated autophagic cell death in A431 cells. Importantly, DHM decreased lncRNA MALAT1 expression and MALAT1 overexpression abrogated the effects of DHM on TFEB-dependent autophagy both in vitro and in vivo. Taken together, DHM induces CSCC cell death via inducing excessive autophagy, which is mediated through the
Url:
DOI: 10.7150/jca.32807
PubMed: 31413743
PubMed Central: 6691703
Affiliations:
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TFEB-dependent autophagic cell death in cutaneous squamous cell carcinoma</title>
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<front><div type="abstract" xml:lang="en"><p>Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer. Dihydromyricetin (DHM), a Rattan tea extract, has been shown to have antitumor activity with no obvious toxicity to normal cells in vitro and in vivo. However, its efficacy in the treatment of CSCC and the underlying antitumor mechanism has not been fully elucidated yet. In our study, DHM increased autophagic flux in the A431 cells, as evidenced by the upregulation of LC3-II and downregulation of P62/SQSTM1. Moreover, the pharmacological or genetic blocking autophagy decreased DHM-induced cell death, indicating DHM triggered autophagic cell death in A431 cells. Specifically, DHM induced TFEB<sup>(Ser142)</sup>
de-phosphorylation, activated TFEB nuclear translocation and increased of TFEB reporter activity, which contributed to the expression of autophagy-related genes and subsequent initiated autophagic cell death in A431 cells. Importantly, DHM decreased lncRNA MALAT1 expression and MALAT1 overexpression abrogated the effects of DHM on TFEB-dependent autophagy both in vitro and in vivo. Taken together, DHM induces CSCC cell death via inducing excessive autophagy, which is mediated through the <italic>MALAT1</italic>
-TFEB pathway. Therefore, DHM may be beneficial for the development of chemotherapy for CSCC.</p>
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</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
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</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Tan, Miduo" sort="Tan, Miduo" uniqKey="Tan M" first="Miduo" last="Tan">Miduo Tan</name>
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<name sortKey="Chen, Xiang" sort="Chen, Xiang" uniqKey="Chen X" first="Xiang" last="Chen">Xiang Chen</name>
<name sortKey="Dong, Dan" sort="Dong, Dan" uniqKey="Dong D" first="Dan" last="Dong">Dan Dong</name>
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<name sortKey="Ouyang, Wei" sort="Ouyang, Wei" uniqKey="Ouyang W" first="Wei" last="Ouyang">Wei Ouyang</name>
<name sortKey="Tang, Manling" sort="Tang, Manling" uniqKey="Tang M" first="Manling" last="Tang">Manling Tang</name>
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</tree>
</affiliations>
</record>
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