J Cancer 2019; 10(18):4245-4255. doi:10.7150/jca.32807

Research Paper

Dihydromyricetin induced lncRNA MALAT1-TFEB-dependent autophagic cell death in cutaneous squamous cell carcinoma

Miduo Tan1,*, Bin Jiang2,*, Haihua Wang3, Wei Ouyang4, Xiang Chen5, Taoli Wang6, Dan Dong7, Shun Yi8, Jiansheng Yi1, Yan Huang1, Manling Tang5, Yan Xiao9, Zuiming Jiang5✉, Wei Zhou1✉

1. Surgery Department of Galactophore, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.
2. Department of Plastic Surgery, The Second Hospital University of South China, Hengyang, 421001, China.
3. Department of Burns and Plastic Surgery, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.
4. Department of Oncology, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.
5. Clinical Laboratory Center, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.
6. Department of Pathology, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.
7. Department of Dermatology, The Second Hospital University of South China, Hengyang, 421001, China
8. Department of General surgery, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China
9. Department of Otolaryngology, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China
* Authors contributed equally to this work.

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.

Keywords: Dihydromyricetin, autophagy, TFEB, MALAT1, Cutaneous squamous cell carcinoma

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How to cite this article:
Tan M, Jiang B, Wang H, Ouyang W, Chen X, Wang T, Dong D, Yi S, Yi J, Huang Y, Tang M, Xiao Y, Jiang Z, Zhou W. Dihydromyricetin induced lncRNA MALAT1-TFEB-dependent autophagic cell death in cutaneous squamous cell carcinoma. J Cancer 2019; 10(18):4245-4255. doi:10.7150/jca.32807. Available from http://www.jcancer.org/v10p4245.htm