Abstract：
BACKGROUND:Gemcitabine-based chemotherapy is the standard treatment for pancreatic cancer. However, the issue of resistance remains unresolved. The aim of this study was to identify microRNAs (miRNAs) that govern the resistance to gemcitabine in pancreatic cancer. METHODS:miRNA microarray analysis using gemcitabine-resistant clones of MiaPaCa2 (MiaPaCa2-RGs), PSN1 (PSN1-RGs), and their parental cells (MiaPaCa2-P, PSN1-P) was conducted. Changes in the anti-cancer effects of gemcitabine were studied after gain/loss-of-function analysis of the candidate miRNA. Further assessment of the putative target gene was performed in vitro and in 66 pancreatic cancer clinical samples. RESULTS:miR-320c expression was significantly higher in MiaPaCa2-RGs and PSN1-RGs than in their parental cells. miR-320c induced resistance to gemcitabine in MiaPaCa2. Further experiments showed that miR-320c-related resistance to gemcitabine was mediated through SMARCC1, a core subunit of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex. In addition, clinical examination revealed that only SMARCC1-positive patients benefited from gemcitabine therapy with regard to survival after recurrence (P=0.0463). CONCLUSION:The results indicate that miR-320c regulates the resistance of pancreatic cancer cells to gemcitabine through SMARCC1, suggesting that miR-320c/SMARCC1 could be suitable for prediction of the clinical response and potential therapeutic target in pancreatic cancer patients on gemcitabine-based therapy.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Iwagami Y,Eguchi H,Nagano H,Akita H,Hama N,Wada H,Kawamoto K,Kobayashi S,Tomokuni A,Tomimaru Y,Mori M,Doki Ydoi
10.1038/bjc.2013.320subject
Has Abstractpub_date
2013-07-23 00:00:00pages
502-11issue
2eissn
0007-0920issn
1532-1827pii
bjc2013320journal_volume
109pub_type
杂志文章abstract：BACKGROUND:Systemic inflammatory response (SIR) is important in the relationship between the tumour, the host, and outcome in cancer patients. However, limited data exist regarding the prognostic significance of SIR in bladder cancer. We investigate the utility of pretreatment SIR in patients with urothelial carcinoma ...
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doi：10.1038/bjc.2014.631
更新日期：2015-02-03 00:00:00
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pub_type： 杂志文章
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doi：10.1038/sj.bjc.6690323
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doi：10.1038/sj.bjc.6690242
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更新日期：1999-10-01 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1986.224
更新日期：1986-10-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/bjc.1986.270
更新日期：1986-12-01 00:00:00
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更新日期：2003-03-10 00:00:00
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pub_type： 杂志文章
doi：10.1038/bjc.1985.3
更新日期：1985-01-01 00:00:00
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更新日期：2005-03-28 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-019-0563-x
更新日期：2019-10-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/bjc.1995.146
更新日期：1995-04-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/bjc.1987.117
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pub_type： 杂志文章,多中心研究,随机对照试验
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更新日期：2010-08-24 00:00:00
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doi：10.1038/bjc.1996.424
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更新日期：1996-03-01 00:00:00
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