Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Loss of EMP2 Inhibits Melanogenesis of MNT1 Melanoma Cells via Regulation of TRP-2

  • Enkhtaivan, Enkhmend (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Kim, Hyun Ji (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Kim, Boram (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Byun, Hyung Jung (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Yu, Lu (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Nguyen, Tuan Minh (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Nguyen, Thi Ha (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Do, Phuong Anh (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Kim, Eun Ji (Lillehei Heart Institute, University of Minnesota) ;
  • Kim, Kyung Sung (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Huy, Hieu Phung (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Rahman, Mostafizur (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Jang, Ji Yun (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Rho, Seung Bae (National Cancer Center) ;
  • Lee, Ho (National Cancer Center) ;
  • Kang, Gyeoung Jin (Lillehei Heart Institute, University of Minnesota) ;
  • Park, Mi Kyung (National Cancer Center) ;
  • Kim, Nan-Hyung (Department of Dermatology, Dongguk University Ilsan Hospital) ;
  • Choi, Chang Ick (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Lee, Kyeong (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Han, Hyo Kyung (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Cho, Jungsook (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University) ;
  • Lee, Ai Young (Department of Dermatology, Dongguk University Ilsan Hospital) ;
  • Lee, Chang Hoon (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University)
  • Received : 2022.01.03
  • Accepted : 2022.02.07
  • Published : 2022.03.01
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Abstract

Melanogenesis is the production of melanin from tyrosine by a series of enzyme-catalyzed reactions, in which tyrosinase and DOPA oxidase play key roles. The melanin content in the skin determines skin pigmentation. Abnormalities in skin pigmentation lead to various skin pigmentation disorders. Recent research has shown that the expression of EMP2 is much lower in melanoma than in normal melanocytes, but its role in melanogenesis has not yet been elucidated. Therefore, we investigated the role of EMP2 in the melanogenesis of MNT1 human melanoma cells. We examined TRP-1, TRP-2, and TYR expression levels during melanogenesis in MNT1 melanoma cells by gene silencing of EMP2. Western blot and RT-PCR results confirmed that the expression levels of TYR and TRP-2 were decreased when EMP2 expression was knocked down by EMP2 siRNA in MNT1 cells, and these changes were reversed when EMP2 was overexpressed. We verified the EMP2 gene was knocked out of the cell line (EMP2 CRISPR/Cas9) by using a CRISPR/Cas9 system and found that the expression levels of TRP-2 and TYR were significantly lower in the EMP2 CRISPR/Cas9 cell lines. Loss of EMP2 also reduced migration and invasion of MNT1 melanoma cells. In addition, the melanosome transfer from the melanocytes to keratinocytes in the EMP2 KO cells cocultured with keratinocytes was reduced compared to the cells in the control coculture group. In conclusion, these results suggest that EMP2 is involved in melanogenesis via the regulation of TRP-2 expression.

Keywords

Acknowledgement

This study was supported by a grant from the Basic Science Research Program through the NRF (NRF-2018R1A5A2023127, NRF-2020R1A2C3004973, and NRF-2020M3E5E20383 56), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Korea (HP20C0131), and the BK21 FOUR program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (MOE, Korea).

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