Development of novel miR-129 mimics with enhanced efficacy to eliminate chemoresistant colon cancer stem cells

Ning Wu; Andrew Fesler; Hua Liu; Jingfang Ju

doi:10.18632/oncotarget.22322

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Research Papers:

Development of novel miR-129 mimics with enhanced efficacy to eliminate chemoresistant colon cancer stem cells

Ning Wu, Andrew Fesler, Hua Liu and Jingfang Ju _

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Oncotarget. 2018; 9:8887-8897. https://doi.org/10.18632/oncotarget.22322

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Abstract

Ning Wu1,2,*, Andrew Fesler1,*, Hua Liu1,* and Jingfang Ju1

1Department of Pathology, School of Medicine, Stony Brook University, Stony Brook, NY, USA

2Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China

*These authors have contributed equally to this work

Correspondence to:

Jingfang Ju, email: [email protected]

Keywords: 5-fluorouracil; miR-129; colorectal cancer; cancer stem cells; chemoresistance

Received: September 07, 2017 Accepted: October 13, 2017 Published: November 06, 2017

ABSTRACT

Background: Resistance to 5-Fluorouracil (5-FU) based chemotherapy is the major reason for failure of treating patients with advanced colorectal cancer.

Materials and methods: In this study, we developed a novel miR-129 mimic with potent efficacy in eliminating resistant colon cancer stem cells both in vitro and in vivo. We integrated 5-FU into miR-129 by replacing Uracil (U) to generate 5-FU-miR-129 mimics (Mimic-1).

Results: Mimic-1 is a strong therapeutic candidate with a number of unique features. Mimic-1 can be delivered to cancer cells without any transfection reagents (e.g. lipids, viral vector, nanoparticles). Mimic-1 is more potent at inhibiting cell proliferation and inducing cell cycle arrest at G1 phase than native miR-129 and the other mimics tested, while retaining target specificity. Mimic-1 prevents colon cancer metastasis in vivo without toxicity.

Conclusion: This represents a significant advancement in the development of a nontoxic and highly potent miRNA based cancer therapeutics and establishes a foundation for further developing Mimic-1 as a novel anti-cancer therapeutic for treating colorectal cancer.

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PII: 22322

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Research Papers:

Development of novel miR-129 mimics with enhanced efficacy to eliminate chemoresistant colon cancer stem cells

Abstract