MiR-10a-5p targets TFAP2C to promote gemcitabine resistance in pancreatic ductal adenocarcinoma.
MiR-10a-5p targets TFAP2C to promote gemcitabine resistance in pancreatic ductal adenocarcinoma.
复制标题
MiR-10a-5p 靶向 TFAP2C 促进胰腺导管腺癌吉西他滨耐药
DOI：
10.1186/s13046-018-0739-x
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发表时间：
2018-04-03
期刊：
影响因子：
--
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Xiong G;Huang H;Feng M;Yang G;Zheng S;You L;Zheng L;Hu Y;Zhang T;Zhao Y
背景：microRNAs通过调控靶基因，在人胰腺导管腺癌的发生和耐药中发挥重要作用。以往的研究表明，microRNA-10a-5p(miR-10a-5p)在PDAC中高表达，并作为癌基因促进PDAC细胞的转移行为。然而，miR-10a-5p在PDAC耐药中的作用尚不清楚。结果在体外和体内，miR-10a-5p在耐吉西他滨的PDAC细胞中表达上调，并增强PDAC细胞对吉西他滨的耐药性。同时，我们还发现miR-10a-5p促进了PDAC细胞的迁移和侵袭能力。接下来，我们证实转录因子激活蛋白2-γ(Tfap2c)是miR-10a-5p的靶标，而Tfap2c的过度表达使PDAC细胞对由miR-10a-5p启动的吉西他滨重新敏感。进一步的研究表明，Tfap2c还降低了PDAC细胞的迁移和侵袭能力。生存分析显示miR-10a-5p高表达和Tfap2c低表达均是PDAC患者独立的预后不良因素。结论miR-10a-5p/Tfap2c可能成为PDAC新的治疗靶点和预后指标。
BackgroundBy regulating target genes, microRNAs play essential roles in carcinogenesis and drug resistance in human pancreatic ductal adenocarcinoma (PDAC). Previous studies have shown that microRNA-10a-5p (miR-10a-5p) is overexpressed in PDAC and acts as an oncogene to promote the metastatic behavior of PDAC cells. However, the role of miR-10a-5p in PDAC chemoresistance remains unclear.MethodsThe effects of miR-10a-5p on biological behaviors were analyzed. MiR-10a-5p and TFAP2C levels in tissues were detected, and the clinical value was evaluated.ResultsWe found that miR-10a-5p is up-regulated in gemcitabine-resistant PDAC cells and enhances PDAC cell gemcitabine resistance in vitro and vivo. Meanwhile, we also determined that miR-10a-5p promotes the migratory and invasive ability of PDAC cells. Next, we confirmed that transcription factor activating protein 2 gamma (TFAP2C) is a target of miR-10a-5p, and TFAP2C overexpression resensitizes PDAC cells to gemcitabine, which is initiated by miR-10a-5p. Further studies revealed that TFAP2C also decreased PDAC cell migration and invasion capability. Finally, survival analysis demonstrated that high miR-10a-5p expression levels and low TFAP2C expression levels were both independent adverse prognostic factors in patients with PDAC.ConclusionTogether, these results indicate that miR-10a-5p/TFAP2C may be new therapeutic target and prognostic marker in PDAC.
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影响因子：
3.6
作者：
Hudson, Jena;Duncavage, Eric;Tamburrino, Anna;Salerno, Paolo;Xi, Liqiang;Raffeld, Mark;Moley, Jeffrey;Chernock, Rebecca D.
通讯作者：
Chernock, Rebecca D.
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3.7
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Yu J
影响因子：
254.7
作者：
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通讯作者：
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影响因子：
8.4
作者：
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通讯作者：
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