Silencing of Dicer enhances dacarbazine resistance in melanoma cells by inhibiting ADSL expression

Yu Wen Yeh, Tung Wei Hsu, Yen Hao Su, Chih Hsin Wang, Po Hsiang Liao, Ching Feng Chiu, Po Chen Tseng, Tim Mo Chen, Woan Ruoh Lee, Yuan Sheng Tzeng

研究成果: 雜誌貢獻文章同行評審

摘要

Dacarbazine (DTIC) is the primary first-line treatment for advanced-stage metastatic melanoma; thus, DTIC resistance is poses a major challenge. Therefore, investigating the mechanism underlying DTIC resistance must be investigated. Dicer, a type III cytoplasmic endoribonuclease, plays a pivotal role in the maturation of miRNAs. Aberrant Dicer expression may contribute to tumor progression, clinical aggressiveness, and poor prognosis in various tumors. Dicer inhibition led to a reduction in DTIC sensitivity and an augmentation in stemness in melanoma cells. Clinical analyses indicated a low Dicer expression level as a predictor of poor prognosis factor. Metabolic alterations in tumor cells may interfere with drug response. Adenylosuccinate lyase (ADSL) is a crucial enzyme in the purine metabolism pathway. An imbalance in ADSL may interfere with the therapeutic efficacy of drugs. We discovered that DTIC treatment enhanced ADSL expression and that Dicer silencing significantly reduced ADSL expression in melanoma cells. Furthermore, ADSL overexpression reversed Dicer silencing induced DTIC resistance and cancer stemness. These findings indicate that Dicer-mediated ADSL regulation influences DTIC sensitivity and stemness in melanoma cells.
原文英語
頁(從 - 到)12873-12889
頁數17
期刊Aging
15
發行號22
DOIs
出版狀態已發佈 - 2023

ASJC Scopus subject areas

  • 老化
  • 細胞生物學

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