作者: Buyuan Chen , Xinji Chen , Xiwei Wu , Xiaoling Wang , Yingjia Wang
DOI: 10.1016/J.CANLET.2014.09.034
关键词:
摘要: MicroRNA-21 is dysregulated in many cancers and fibrotic diseases. Since miR-21 suppresses several tumor suppressor anti-apoptotic genes, it considered a cancer therapeutic target. Antisense oligonucleotides are commonly used to inhibit miRNA; however, blocking miRNA function via an antagomir temporary, often only achieves partial knock-down, may be complicated by off-target effects. Here, we transcription activator-like effector nucleases (TALENs) disrupt cancerous cells. Individual deletion clones were screened isolated without drug selection. Sequencing quantitative RT-PCR identified with no expression. The loss of led subtle but global increases mRNAs containing target sequences. Cells became more sensitive cisplatin less transformed culture mouse xenografts. In addition the increase PDCD4 PTEN protein, for COL4A1, JAG1, SERPINB5/Maspin, SMAD7, TGFBI - all targets involved TGFβ fibrosis regulation significantly upregulated knockout Gene ontology pathway analysis suggested that cell-environment interactions involving extracellular matrix can important pathogenic mechanism. study also demonstrates value using TALEN-mediated microRNA gene disruption human pathobiological studies.