Role of Dicer in regulating oxaliplatin resistance of colon cancer cells

Hui Huang Lai, Li Jyuan Lin, Liang Yi Hung, Pai Sheng Chen

研究成果: Article同行評審

14 引文 斯高帕斯(Scopus)

摘要

Colorectal cancer (CRC) is a major health problem due to its high mortality rate. The incidence of CRC is increasing in young individuals. Oxaliplatin (OXA) is an approved third-generation drug and is used for first-line chemotherapy in CRC. Although current standard chemotherapy improves the overall survival of CRC patients, an increasing number of reports of OXA resistance in CRC therapy indicates that resistance has become an urgent problem in clinical applications. Dicer is a critical enzyme involved in miRNA maturation. The expression of Dicer has been reported to be involved in the resistance to various drugs in cancer. In the present study, we aimed to investigate the role of Dicer in OXA resistance in CRC. We found that OXA treatment inhibited Dicer expression through decreasing the protein stability. OXA-induced Dicer protein degradation occurred through both proteasomal and lysosomal proteolysis, while the CHIP E3 ligase was involved in OXA-mediated Dicer ubiquitination and degradation. We established stable OXA-resistant clones from CRC cells, and observed that the CHIP E3 ligase was decreased, along with the increased Dicer expression in OXA-resistant cells. Knockdown of Dicer resensitized CRC cells to OXA treatment. In this study, we have revealed the role of miRNA biogenesis factors in OXA resistance in CRC cells.

原文English
頁(從 - 到)87-93
頁數7
期刊Biochemical and Biophysical Research Communications
506
發行號1
DOIs
出版狀態Published - 2018 11月 17

All Science Journal Classification (ASJC) codes

  • 生物物理學
  • 生物化學
  • 分子生物學
  • 細胞生物學

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