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Targeted Inhibition of the miR-199a214 Cluster by CRISPR Interference Augments the Tumor Tropism of Human Induced Pluripotent Stem Cell-Derived Neural Stem Cells under Hypoxic Condition
Joint Authors
Luo, Yumei
Zhu, Detu
Wang, Shu
Xu, Xuehu
An, Xiuli
Sun, Xiaofang
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2015), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-11-14
Country of Publication
Egypt
No. of Pages
8
Abstract EN
The human induced pluripotent stem cell (hiPSC) provides a breakthrough approach that helps overcoming ethical and allergenic challenges posed in application of neural stem cells (NSCs) in targeted cancer gene therapy.
However, the tumor-tropic capacity of hiPSC-derived NSCs (hiPS-NSCs) still has much room to improve.
Here we attempted to promote the tumor tropism of hiPS-NSCs by manipulating the activity of endogenous miR-199a/214 cluster that is involved in regulation of hypoxia-stimulated cell migration.
We first developed a baculovirus-delivered CRISPR interference (CRISPRi) system that sterically blocked the E-box element in the promoter of the miR-199a/214 cluster with an RNA-guided catalytically dead Cas9 (dCas9).
We then applied this CRISPRi system to hiPS-NSCs and successfully suppressed the expression of miR-199a-5p, miR-199a-3p, and miR-214 in the microRNA gene cluster.
Meanwhile, the expression levels of their targets related to regulation of hypoxia-stimulated cell migration, such as HIF1A, MET, and MAPK1, were upregulated.
Further migration assays demonstrated that the targeted inhibition of the miR-199a/214 cluster significantly enhanced the tumor tropism of hiPS-NSCs both in vitro and in vivo.
These findings suggest a novel application of CRISPRi in NSC-based tumor-targeted gene therapy.
American Psychological Association (APA)
Luo, Yumei& Xu, Xuehu& An, Xiuli& Sun, Xiaofang& Wang, Shu& Zhu, Detu. 2016. Targeted Inhibition of the miR-199a214 Cluster by CRISPR Interference Augments the Tumor Tropism of Human Induced Pluripotent Stem Cell-Derived Neural Stem Cells under Hypoxic Condition. Stem Cells International،Vol. 2016, no. 2016, pp.1-8.
https://search.emarefa.net/detail/BIM-1116405
Modern Language Association (MLA)
Luo, Yumei…[et al.]. Targeted Inhibition of the miR-199a214 Cluster by CRISPR Interference Augments the Tumor Tropism of Human Induced Pluripotent Stem Cell-Derived Neural Stem Cells under Hypoxic Condition. Stem Cells International Vol. 2016, no. 2016 (2015), pp.1-8.
https://search.emarefa.net/detail/BIM-1116405
American Medical Association (AMA)
Luo, Yumei& Xu, Xuehu& An, Xiuli& Sun, Xiaofang& Wang, Shu& Zhu, Detu. Targeted Inhibition of the miR-199a214 Cluster by CRISPR Interference Augments the Tumor Tropism of Human Induced Pluripotent Stem Cell-Derived Neural Stem Cells under Hypoxic Condition. Stem Cells International. 2016. Vol. 2016, no. 2016, pp.1-8.
https://search.emarefa.net/detail/BIM-1116405
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1116405