Loss of EMP2 Inhibits Melanogenesis of MNT1 Melanoma Cells via Regulation of TRP-2

Enkhmend Enkhtaivan, Hyun Ji Kim, Boram Kim, Hyung Jung Byun, Lu Yu, Tuan Minh Nguyen, Thi Ha Nguyen, Phuong Anh Do, Eun Ji Kim, Kyung Sung Kim, Hiệu Phùng Huy, Mostafizur Rahman, Ji Yun Jang, Seung Bae Rho, Ho Lee, Gyeoung Jin Kang, Mi Kyung Park, Nan Hyung Kim, Chang Ick Choi, Kyeong LeeHyo Kyung Han, Jungsook Cho, Ai Young Lee, Chang Hoon Lee

Research output: Contribution to journalArticlepeer-review

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 signifi-cantly 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.

Original languageEnglish (US)
Pages (from-to)203-211
Number of pages9
JournalBiomolecules and Therapeutics
Volume30
Issue number2
DOIs
StatePublished - Mar 2022

Bibliographical note

Funding Information:
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).

Funding Information:
This study was supported by a grant from the Ba-sic 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).

Publisher Copyright:
© 2022 The Korean Society of Applied Pharmacology.

Keywords

  • EMP2
  • Melanogenesis
  • Melanosome transfer
  • TRP-1
  • TRP-2
  • TYR

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