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Beyond Thymidylate Synthase and Dihydrofolate Reductase: Impact of Non-coding microRNAs in anticancer chemoresistance

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6 Scopus citations

Abstract

Chemoresistance is one of the major reasons for the failure of anticancer chemotherapy in treating advanced stage cancer. The mechanism of chemoresistance to fluoropyrimidines and antifolates has been extensively investigated in the past 40 years. It has been well established that thymidylate synthase (TYMS, TS) and dihydrofolate reductase (DHFR) are two major targets for fluoropyrimidines and antifolates, respectively. The regulatory mechanism of TS and DHFR expression is rather complex involving transcriptional, post-transcriptional and translational regulations. Our recent understanding of the chemoresistance mechanism has been extended beyond the simple one target/drug view. In this review, we will focus on the recent advancement of non-coding microRNAs (miRNAs) in contributing to the regulations of TS and DHFR expression, and to the chemoresistance mechanism of fluoropyrimidines and antifolates.

Original languageEnglish
Pages (from-to)118-123
Number of pages6
JournalCurrent Enzyme Inhibition
Volume8
Issue number2
DOIs
StatePublished - Sep 2012

Keywords

  • 5-fluorouracil
  • Chemoresistance
  • Dihydrofolate reductase
  • Methotrexate
  • MicroRNA
  • Thymidylate synthase
  • Translational control

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