@article{b43ba3dca65d49139c677919b1328d43,
title = "ERK-mediated transcriptional activation of Dicer is involved in gemcitabine resistance of pancreatic cancer",
abstract = "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.",
keywords = "Dicer, ERK, gemcitabine resistance, pancreatic cancer, Sp1",
author = "Su, {Yen Hao} and Hsu, {Tung Wei} and Chen, {Hsin An} and Su, {Chih Ming} and Huang, {Ming Te} and Chuang, {Ta Hsien} and {Leo Su}, J. and Hsieh, {Chia Ling} and Chiu, {Ching Feng}",
note = "Funding Information: We thank the National RNAi Core Facility (Academia Sinica, Taiwan) for providing specific shRNAs, and thank Dr. Chih‐Chen Hong (National Health Research Institutes, Taiwan) for offering promoter constructions, Prof. Wun‐Shaing Wayne Chang and Prof. Li‐Tzong Chen, the National Institute of Cancer Research (National Health Research Institutes, Taiwan) for kindly providing gemcitabine‐resistant PANC‐1 (PANC‐1/GEM100 and PANC‐1/GEM1500) cells, and thank Ms. Fang‐Yu Tsai, Dr. I‐Shou Chang and Dr. Shih‐Sheng Jiang of the Taiwan Bioinformatics Institute Core Facility for assistance on using the Oncomine database (National Core Facility Program for Biotechnology, NSC‐100‐2319‐B‐400‐001), and the results shown here are in part based upon data generated by the TCGA Research Network ( http://cancergenome.nih.gov/ ). This study was financially supported by the Ministry of Science and Technology (MOST) in Taiwan (MOST 104‐2321‐B‐038‐012‐MY3, 107‐2320‐B‐038‐065, 108‐2320‐B‐038‐015, and 109‐2314‐B‐866‐001‐MY3); the China Medical University (CMU108‐S‐13); the Taipei Medical University‐Shuang Ho Hospital, Ministry of Health and Welfare grant from Taiwan (104TMU‐SHH‐01‐3); the Taipei Medical University Research Grants for Newly Hired Faculty (TMU106‐AE1‐B38), and the TMU Research Center of Cancer Translational Medicine from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan. Dicer Publisher Copyright: {\textcopyright} 2020 Wiley Periodicals LLC Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2021",
month = jun,
doi = "10.1002/jcp.30159",
language = "English",
volume = "236",
pages = "4420--4434",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "6",
}
