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ERK‐mediated transcriptional activation of Dicer is involved in gemcitabine resistance of pancreatic cancer
Author(s) -
Su YenHao,
Hsu TungWei,
Chen HsinAn,
Su ChihMing,
Huang MingTe,
Chuang TaHsien,
Leo Su J.,
Hsieh ChiaLing,
Chiu ChingFeng
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30159
Subject(s) - dicer , gemcitabine , pancreatic cancer , cancer research , microrna , mapk/erk pathway , cancer , biology , medicine , microbiology and biotechnology , signal transduction , small interfering rna , cell culture , transfection , genetics , gene
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.