Oncotarget

Research Papers:

Upregulation of microRNA-125b by G-CSF promotes metastasis in colorectal cancer

Xinghua Zhang, Xiao Ma, Huaying An, Changqing Xu, Wenjo Cao, Wei Yuan and Jie Ma _

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Oncotarget. 2017; 8:50642-50654. https://doi.org/10.18632/oncotarget.16892

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Abstract

Xinghua Zhang1,*, Xiao Ma1,*, Huaying An1, Changqing Xu2, Wenjo Cao3, Wei Yuan1,4 and Jie Ma1,4,5

1State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China

2Department of Gastroenterology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China

3Department of Science, University of British Columbia, Vancouver, Canada

4Clinical Immunology Center, Chinese Academy of Medical Science, Beijing, China

5Department of Biotherapy, Beijing Hospital, National Center of Gerontology, Beijing, China

*These authors are contributed equally to this work

Correspondence to:

Wei Yuan, email: yuanwei7568@163.com

Jie Ma, email: majie@cicams.ac.cn

Keywords: colorectal cancer, microRNA-125b, MCL1, G-CSF, metastasis

Received: November 25, 2016     Accepted: March 27, 2017     Published: April 06, 2017

ABSTRACT

Although there are reports of miR-125b being dysregulated in colorectal cancer (CRC) and associated with CRC progression, little is known about its intrinsic regulatory mechanisms. Here we detected the expression of miR-125b in CRC tissues, subsequently investigated the effect of miR-125b on the proliferation, apoptosis, cell cycle and metastasis on CRC cells. Our results showed that the expression of miR-125b was significantly decreased in CRC tissues comparing to adjacent tissues. However, with the stimulation of Granulocyte colony-stimulating factor (G-CSF), which was highly expressed in CRC tissues, the expression of miR-125b could be improved. Analysis of patient samples revealed that miR-125b presented a clear association with poor differentiation, positive lymph node metastasis, and advanced TNM stage. Overexpression of miR-125b inhibited cell proliferation, triggered G2/M cell cycle arrest, induced subsequent apoptosis, and promoted cell migration and invasion. Moreover, luciferase reporter assays and western blot clarified that the myeloid cell leukemia 1 (MCL1) was a direct target of miR-125b. Thus overexpression of MCL1 attenuated the pro-metastasis function of miR-125b in CRC cell lines. In addition, the protein expression level of MCL1 was decreased in CRC tissues from patients with positive lymph node metastasis, which had high miR-125b expression. Collectively, our study suggested that miR-125b induced by G-CSF plays a promoting role in the metastasis of CRC by targeting MCL1, which may serve as a novel therapeutic target for CRC metastasis.


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