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

Miduo Tan1, Bin Jiang2, Haihua Wang3

  • 1Surgery Department of Galactophore, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412000, China.

Journal of Cancer
|August 16, 2019
PubMed

Insights

Dihydromyricetin (DHM) triggers cancer cell death in cutaneous squamous cell carcinoma (CSCC) by inducing excessive autophagy through the MALAT1-TFEB pathway. This finding suggests DHM

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Cutaneous squamous cell carcinoma (CSCC) is a prevalent skin cancer.
  • Dihydromyricetin (DHM), a natural compound, exhibits antitumor properties.
  • The precise mechanism of DHM's action in CSCC requires further investigation.

Purpose of the Study:

  • To elucidate the antitumor mechanism of DHM in CSCC.
  • To investigate DHM's effect on autophagy and related pathways in CSCC cells.
  • To determine the role of MALAT1 and TFEB in DHM-induced cell death.

Main Methods:

  • Assessed autophagic flux using LC3-II and P62/SQSTM1 markers in A431 cells.
  • Investigated DHM's impact on TFEB phosphorylation, nuclear translocation, and reporter activity.
  • Examined the role of MALAT1 in DHM-mediated autophagy and cell death via overexpression studies.
  • Utilized pharmacological and genetic autophagy inhibition to assess DHM's effects.

Main Results:

  • DHM significantly increased autophagic flux in A431 cells.
  • Autophagy inhibition reduced DHM-induced cell death, confirming autophagic cell death.
  • DHM de-phosphorylated TFEB at Ser142, promoting its nuclear translocation and activating autophagy-related gene expression.
  • DHM decreased MALAT1 expression, while MALAT1 overexpression counteracted DHM's effects on TFEB-dependent autophagy.

Conclusions:

  • DHM induces autophagic cell death in CSCC through the MALAT1-TFEB pathway.
  • DHM's mechanism involves activating TFEB-dependent autophagy by downregulating MALAT1.
  • Dihydromyricetin shows potential as a therapeutic agent for cutaneous squamous cell carcinoma.

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