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Dihydromyricetin induced lncRNA MALAT1-TFEB-dependent autophagic cell death in cutaneous squamous cell carcinoma.
J Cancer 2019; 10(18):4245-4255JC

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 MALAT1-TFEB pathway. Therefore, DHM may be beneficial for the development of chemotherapy for CSCC.

Authors+Show Affiliations

Surgery Department of Galactophore, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.Department of Plastic Surgery, The Second Hospital University of South China, Hengyang, 421001, China.Department of Burns and Plastic Surgery, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.Department of Oncology, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.Clinical Laboratory Center, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.Department of Pathology, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.Department of Dermatology, The Second Hospital University of South China, Hengyang, 421001, China.Department of General surgery, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.Surgery Department of Galactophore, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.Surgery Department of Galactophore, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.Clinical Laboratory Center, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.Department of Otolaryngology, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.Clinical Laboratory Center, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.Surgery Department of Galactophore, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31413743

Citation

Tan, Miduo, et al. "Dihydromyricetin Induced lncRNA MALAT1-TFEB-dependent Autophagic Cell Death in Cutaneous Squamous Cell Carcinoma." Journal of Cancer, vol. 10, no. 18, 2019, pp. 4245-4255.
Tan M, Jiang B, Wang H, et al. Dihydromyricetin induced lncRNA MALAT1-TFEB-dependent autophagic cell death in cutaneous squamous cell carcinoma. J Cancer. 2019;10(18):4245-4255.
Tan, M., Jiang, B., Wang, H., Ouyang, W., Chen, X., Wang, T., ... Zhou, W. (2019). Dihydromyricetin induced lncRNA MALAT1-TFEB-dependent autophagic cell death in cutaneous squamous cell carcinoma. Journal of Cancer, 10(18), pp. 4245-4255. doi:10.7150/jca.32807.
Tan M, et al. Dihydromyricetin Induced lncRNA MALAT1-TFEB-dependent Autophagic Cell Death in Cutaneous Squamous Cell Carcinoma. J Cancer. 2019;10(18):4245-4255. PubMed PMID: 31413743.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dihydromyricetin induced lncRNA MALAT1-TFEB-dependent autophagic cell death in cutaneous squamous cell carcinoma. AU - Tan,Miduo, AU - Jiang,Bin, AU - Wang,Haihua, AU - Ouyang,Wei, AU - Chen,Xiang, AU - Wang,Taoli, AU - Dong,Dan, AU - Yi,Shun, AU - Yi,Jiansheng, AU - Huang,Yan, AU - Tang,Manling, AU - Xiao,Yan, AU - Jiang,Zuiming, AU - Zhou,Wei, Y1 - 2019/07/10/ PY - 2019/01/04/received PY - 2019/05/26/accepted PY - 2019/8/16/entrez PY - 2019/8/16/pubmed PY - 2019/8/16/medline KW - Cutaneous squamous cell carcinoma KW - Dihydromyricetin KW - MALAT1 KW - TFEB KW - autophagy SP - 4245 EP - 4255 JF - Journal of Cancer JO - J Cancer VL - 10 IS - 18 N2 - 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 MALAT1-TFEB pathway. Therefore, DHM may be beneficial for the development of chemotherapy for CSCC. SN - 1837-9664 UR - https://www.unboundmedicine.com/medline/citation/31413743/Dihydromyricetin_induced_lncRNA_MALAT1-TFEB-dependent_autophagic_cell_death_in_cutaneous_squamous_cell_carcinoma L2 - http://www.jcancer.org/v10p4245.htm DB - PRIME DP - Unbound Medicine ER -