OTUB1 knockdown promotes apoptosis in melanoma cells by upregulating TRAIL expression

Bok Soon Lee, Sung Un Kang, Mei Huang, Yeon Soo Kim, Young Sun Lee, Jae Yong Park, Chul Ho Kim

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Melanoma, the most serious type of skin cancer, exhibits a high risk of metastasis. Although chemotherapeutic treatmentfor metastatic melanoma improves disease outcome and patientsurvival, some patients exhibit resistance or toxicity to the drugtreatment regime. OTUB1 is a deubiquitinating enzyme overexpressedin several cancers. In this study, we investigated theeffects of inhibiting OTUB1 expression on melanoma-cell proliferationand viability and identified the underlying molecularmechanism of action of OTUB1. We did endogenous OTUB1knockdown in melanoma cells using short interfering RNA,and assessed the resulting phenotypes via MTT assays, Westernblotting, and cell-cycle analysis. We identified differentiallyexpressed genes between OTUB1-knockdown cells and controlcells using RNA sequencing and confirmed them via Westernblotting and reverse transcription polymerase chain reaction.Furthermore, we investigated the involvement of apoptotic andcell survival signaling pathways upon OTUB1 depletion. OTUB1depletion in melanoma cells decreased cell viability and causedsimultaneous accumulation of cells in the sub-G1 phase, indicatingan increase in the apoptotic-cell population. RNA sequencingof OTUB1-knockdown cells revealed an increase in thelevels of the apoptosis-inducing protein TRAIL. Additionally,OTUB1-knockdown cells exhibited increased sensitivity toPLX4032, a BRAF inhibitor, implying that OTUB1 and BRAFact collectively in regulating apoptosis.

Original languageEnglish
Pages (from-to)608-613
Number of pages6
JournalBMB reports
Volume54
Issue number12
DOIs
Publication statusPublished - 2021

Bibliographical note

Funding Information:
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No: HR21C1003), and was supported by the National Research Foundation of Korea (Grant No: 2017R1D1A1B03028527 and 2018R1A2B3009008).

Publisher Copyright:
© 2021. by the The Korean Society for Biochemistry and Molecular Biology

Keywords

  • Cell death
  • Melanoma
  • Otub1
  • Plx4032
  • Trail

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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