Antisense Oligonucleotides against miR-21 Inhibit the Growth and Metastasis of Colorectal Carcinoma via the DUSP8 Pathway

Accumulating research has documented that microRNA-21 (miR-21) plays an important role in the development of human colorectal carcinoma (CRC). Our recent work also showed that antisense oligonucleotides (ASOs) against miR-21 can impair the growth of CRC cells in vitro. However, the potential role of...

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Bibliographic Details
Published in:Molecular therapy. Nucleic acids 2018-12, Vol.13, p.244-255
Main Authors: Ding, Tao, Cui, Panpan, Zhou, Ya, Chen, Chao, Zhao, Juanjuan, Wang, Hairong, Guo, Mengmeng, He, Zhixu, Xu, Lin
Format: Article
Language:English
Subjects:
AKT protein
Antisense oligonucleotides
Apoptosis
ASOs
Cancer
Cell migration
Cell proliferation
Colorectal cancer
Colorectal carcinoma
Cyclin-dependent kinases
DUSP8
Experiments
Gene therapy
growth
Kinases
Medical prognosis
Metabolic pathways
Metastases
Metastasis
MicroRNAs
miR-21
miRNA
Signal transduction
Xenografts
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Summary:Accumulating research has documented that microRNA-21 (miR-21) plays an important role in the development of human colorectal carcinoma (CRC). Our recent work also showed that antisense oligonucleotides (ASOs) against miR-21 can impair the growth of CRC cells in vitro. However, the potential role of miR-21 in gene therapy against CRC remains to be fully elucidated. Here, we further observed the effect of ASOs against miR-21 on the growth and metastasis of CRC in vivo using a xenograft model of human CRC. We found that ASOs could effectively inhibit the growth and metastasis of CRC in vivo, accompanied by downregulated expression of miR-21 and reduced transduction of the AKT and ERK pathway. Mechanically, global gene expression analysis showed that the expression of DUSP8, a novel target of miR-21, was upregulated in tumor mass. Furthermore, overexpression of DUSP8 could remarkably suppress the proliferation and migration of CRC cells in vitro. Finally, downregulation of DUSP8 could abrogate the effects of ASOs against miR-21 on the proliferation and migration of CRC cells, as well as altered transduction of the AKT and ERK signaling pathway. Together, these data suggest that ASOs against miRNAs are an attractive and potential therapeutic for the treatment of human CRC and warrant further development.
ISSN:2162-2531
2162-2531
DOI:10.1016/j.omtn.2018.09.004