miR-320c regulates gemcitabine-resistance in pancreatic cancer via SMARCC1.
miR-320c regulates gemcitabine-resistance in pancreatic cancer via SMARCC1.
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DOI：
10.1038/bjc.2013.320
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发表时间：
2013-07-23
影响因子：
8.8
通讯作者：
Doki Y
中科院分区：
文献类型：
--
作者：
Iwagami Y;Eguchi H;Nagano H;Akita H;Hama N;Wada H;Kawamoto K;Kobayashi S;Tomokuni A;Tomimaru Y;Mori M;Doki Y
基于吉西他滨的化疗是胰腺癌的标准治疗方法。然而，抵抗问题仍未解决。本研究的目的是鉴定控制胰腺癌吉西他滨耐药的microRNAs（miRNAs）。使用MiaPaCa 2（MiaPaCa 2-RGs）、PSN 1（PSN 1-RGs）及其亲本细胞（MiaPaCa 2-P、PSN 1-P）的吉西他滨抗性克隆进行miRNA微阵列分析。在对候选miRNA进行功能获得/丧失分析后，研究吉西他滨抗癌作用的变化。在体外和66个胰腺癌临床样本中对推定的靶基因进行了进一步评估。miR-320 c在MiaPaCa 2-RGs和PSN 1-RGs中的表达显著高于其亲本细胞。miR-320 c诱导MiaPaCa 2对吉西他滨的耐药性。进一步的实验表明，miR-320 c相关的吉西他滨耐药是通过SMARCC 1介导的，SMARCC 1是开关/蔗糖不可发酵（SWI/SNF）染色质重塑复合物的核心亚基。此外，临床检查显示，只有SMARCC 1阳性患者在复发后的生存率方面受益于吉西他滨治疗（P=0.0463）。结果表明，miR-320 c通过SMARCC 1调控胰腺癌细胞对吉西他滨的耐药性，提示miR-320 c/SMARCC 1可用于预测胰腺癌患者吉西他滨治疗的临床疗效和潜在治疗靶点。
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. 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. 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). 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.
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影响因子：
3.2
作者：
Duan, Huihan;Jiang, Yiguo;Wu, Yan
通讯作者：
Wu, Yan
DOI：
10.1158/1078-0432.ccr-08-1013
发表时间：
2008-11-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Ougolkov AV;Bilim VN;Billadeau DD
通讯作者：
Billadeau DD
microRNA表达模式在人肝内胆管癌中的作用。
影响因子：
25.7
作者：
Chen, Lei;Yan, He-Xin;Wang, Hong-Yang
通讯作者：
Wang, Hong-Yang
影响因子：
3.7
作者：
DelBove, Jessica;Rosson, Gary;Weissman, Bernard E.
通讯作者：
Weissman, Bernard E.
microRNA miR-34抑制人类胰腺癌肿瘤发射细胞。
影响因子：
3.7
作者：
Ji Q;Hao X;Zhang M;Tang W;Yang M;Li L;Xiang D;Desano JT;Bommer GT;Fan D;Fearon ER;Lawrence TS;Xu L
通讯作者：
Xu L