Oncotarget

Research Papers:

MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells

Hyebin Koh, Hyeri Park, Nisansala Chandimali, Do Luong Huynh, Jiao Jiao Zhang, Mrinmoy Ghosh, Meeta Gera, Nameun Kim, Yesol Bak, Do-Young Yoon, Yang Ho Park, Taeho Kwon and Dong Kee Jeong _

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Oncotarget. 2017; 8:110540-110551. https://doi.org/10.18632/oncotarget.22818

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Abstract

Hyebin Koh1,*, Hyeri Park1,*, Nisansala Chandimali1,*, Do Luong Huynh1, Jiao Jiao Zhang1, Mrinmoy Ghosh1, Meeta Gera1, Nameun Kim1, Yesol Bak2, Do-Young Yoon2, Yang Ho Park3, Taeho Kwon1,4 and Dong Kee Jeong1,4

1Laboratory of Animal Genetic Engineering and Stem Cell Biology, Department of Animal Biotechnology, Faculty of Biotechnology, Jeju National University, Jeju, Republic of Korea

2Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea

3BRM Institute, Seoul, Republic of Korea

4Laboratory of Animal Genetic Engineering and Stem Cell Biology, Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju, Republic of Korea

*These authors have contributed equally to this work

Correspondence to:

Dong Kee Jeong, email: ngejeong@gmail.com

Taeho Kwon, email: taehokwonk@gmail.com

Keywords: cancer stem cells; Muc1-C; BMI-1; microRNA-128; paclitaxel-resistant

Received: September 21, 2017     Accepted: November 13, 2017     Published: November 30, 2017

ABSTRACT

The existence of cancer stem cells (CSCs) is the main reason for failure of cancer treatment caused by drug resistance. Therefore, eradicating cancers by targeting CSCs remains a significant challenge. In the present study, because of the important role of BMI-1 proto-oncogene, polycomb ring finger (BMI-1) and C-terminal Mucin1 (MUC1-C) in tumor growth and maintenance of CSCs, we aimed to confirm that microRNA miR-128, as an inhibitor of BMI-1 and MUC1-C, could effectively suppress paclitaxel (PTX)-resistant lung cancer stem cells. We showed that CSCs have significantly higher expression levels of BMI-1, MUC1-C, stemness proteins, signaling factors, and higher malignancy compared with normal tumor cells. After transfection with miR-128, the BMI-1 and MUC1-C levels in CSCs were suppressed. When miR-128 was stably expressed in PTX-resistant lung cancer stem cells, the cells showed decreased proliferation, metastasis, self-renewal, migration, invasive ability, clonogenicity, and tumorigenicity in vitro and in vivo and increased apoptosis compared with miR-NC (negative control) CSCs. Furthermore, miR-128 effectively decreased the levels of β-catenin and intracellular signaling pathway-related factors in CSCs. MiR-128 also decreased the luciferase activity of MUC1 reporter constructs and reduced the levels of transmembrane MUC1-C and BMI-1. These results suggested miR-128 as an attractive therapeutic strategy for PTX-resistant lung cancer via inhibition of BMI-1 and MUC1-C.


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