Gemcitabine has been a commonly used therapeutic agent for treatment of pancreatic cancer. In the clinic, a growing resistance to gemcitabine has been observed in patients with pancreatic cancer, and investigation of the underlying mechanism of gemcitabine resistance is urgently required. The microRNA (miRNA)-producing enzyme, Dicer, is crucial for the maturation of miRNAs, and is involved in clinical aggressiveness, poor prognosis, and survival outcomes in various cancers, however, the role of Dicer in acquired gemcitabine resistance of pancreatic cancer is still not clear. Here, we found that Dicer expression was significantly increased in gemcitabine-resistant PANC-1 (PANC-1/GEM) cells compared with parental PANC-1 cells and observed a high level of Dicer correlated with increased risk of pancreatic cancer. Suppression of Dicer obviously decreased gemcitabine resistance in PANC-1/GEM cells; consistently, overexpression of Dicer in PANC-1 cells increased gemcitabine resistance. Moreover, we identified that transcriptional factor Sp1 targeted the promoter region of Dicer and found ERK/Sp1 signaling regulated Dicer expression in PANC-1/GEM cells, as well as positively correlated with pancreatic cancer progression and suggest that targeting the ERK/Sp1/Dicer pathway has potential therapeutic value for pancreatic cancer with acquired resistance to gemcitabine.

Original languageEnglish
Pages (from-to)4420-4434
Number of pages15
JournalJournal of Cellular Physiology
Issue number6
Publication statusPublished - Jun 2021


  • Dicer
  • ERK
  • gemcitabine resistance
  • pancreatic cancer
  • Sp1

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology


Dive into the research topics of 'ERK-mediated transcriptional activation of Dicer is involved in gemcitabine resistance of pancreatic cancer'. Together they form a unique fingerprint.

Cite this