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微小RNA-29a缺乏不会改变小鼠胰腺腺泡癌的病程。

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

作者信息

Dooley James, Lagou Vasiliki, Garcia-Perez Josselyn E, Himmelreich Uwe, Liston Adrian

机构信息

VIB Center for Brain and Disease Research, Leuven, Belgium.

KU Leuven-University of Leuven, Department of Microbiology and Immunology, Leuven, Belgium.

出版信息

Oncotarget. 2017 Apr 18;8(16):26911-26917. doi: 10.18632/oncotarget.15850.

Abstract

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.

摘要

癌症的发展涉及多个细胞过程的复杂失调。由于在同时调节多个途径中起关键作用,微小RNA(miR)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。再加上其在胰腺癌细胞系和活检组织中的表达改变,以及在白血病中已知的致癌功能,这些表达数据已将miR-29a确定为参与胰腺癌生物学过程的关键候选miR。在这里,我们使用miR-29a缺陷小鼠和胰腺腺泡癌的TAg模型在体内功能性地测试miR-29a的作用。我们发现miR-29a缺失对胰腺肿瘤的发生或生长没有影响,对荷瘤小鼠的存活也没有影响。这些结果表明,尽管存在差异表达,但在胰腺腺泡癌背景下miR-29a在致癌方面是中性的。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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aba0/5432306/eb337c04feb3/oncotarget-08-26911-g001.jpg

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