miR-29a-deficiency does not modify the course of murine pancreatic acinar carcinoma.

miR-29a-deficiency does not modify the course of murine pancreatic acinar carcinoma.
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DOI:
10.18632/oncotarget.15850
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发表时间:
2017-04-18
期刊:
影响因子:
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通讯作者:
Liston A
Liston A
中科院分区:
其他
文献类型:
--
作者:
Dooley J;Lagou V;Garcia-Perez JE;Himmelreich U;Liston A

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癌症的发展涉及多种细胞过程的复杂失调。 microRNA (miR) 具有同时调节多种途径的关键功能,被认为在致癌形成过程中具有重要作用。 miR-29a 是胰腺中表达最丰富的 miR 之一。结合胰腺癌细胞系和活检中表达的改变以及白血病中已知的致癌功能,该表达数据已确定 miR-29a 是 miR 参与胰腺癌生物学的关键候选者。在这里,我们使用miR-29a缺陷小鼠和胰腺腺泡癌TAg模型来功能测试miR-29a在体内的作用。我们发现 miR-29a 缺失对胰腺肿瘤的发生或生长以及荷瘤小鼠的存活没有影响。这些结果表明,尽管表达存在差异,miR-29a 在胰腺腺泡癌中具有致癌性中性。如果这些结果扩展到其他胰腺癌模型,它们将降低 miR-29a 作为胰腺癌潜在治疗靶点的吸引力。
The development of cancers involves the complex dysregulation of multiple cellular processes. With key functions in simultaneous regulation of multiple pathways, microRNA (miR) are thought to have important roles in the oncogenic formation process. miR-29a is among the most abundantly expressed miR in the pancreas. Together with altered expression in pancreatic cancer cell lines and biopsies, and known oncogenic functions in leukemia, this expression data has identified miR-29a as a key candidate for miR involvement in pancreatic cancer biology. Here we used miR-29a-deficient mice and the TAg model of pancreatic acinar carcinoma to functionally test the role of miR-29a in vivo. We found no impact of miR-29a loss on the development or growth of pancreatic tumours, nor on the survival of tumour-bearing mice. These results suggest that, despite differential expression, miR-29a is oncogenically neutral in the pancreatic acinar carcinoma context. If these results are extended to other models of pancreatic cancer, they would reduce the attractiveness of miR-29a as a potential therapeutic target in pancreatic cancer.