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Cancer Lett. 2018 Mar 1;416:31-41. doi: 10.1016/j.canlet.2017.12.018. Epub 2017 Dec 14.

Hypoxia-induced microRNA-590-5p promotes colorectal cancer progression by modulating matrix metalloproteinase activity.

Author information

1
Department of Microbiology, College of Medicine, Inha University, Incheon 22212, Republic of Korea; Hypoxia-related Disease Research Center, College of Medicine, Inha University, Incheon 22212, Republic of Korea.
2
Hypoxia-related Disease Research Center, College of Medicine, Inha University, Incheon 22212, Republic of Korea; Department of Biomedical Sciences, College of Medicine, Inha University, Incheon 22212, Republic of Korea.
3
Department of Pathology, College of Medicine, Inha University, Incheon 400-712, Republic of Korea.
4
Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea.
5
Gastroenterology and Hepatology, National Center of Efficacy Evaluation for the Development of Health Products Targeting Digestive Disorders (NCEED), Inha University School of Medicine, Incheon, Republic of Korea.
6
Hypoxia-related Disease Research Center, College of Medicine, Inha University, Incheon 22212, Republic of Korea; Department of Molecular Medicine, Inha University College of Medicine, Incheon, Republic of Korea.
7
Department of Pharmacology, Chonnam National University Medical School, Hak-Dong 5, Dong-Ku, Kwangju 61469, Republic of Korea.
8
Department of Microbiology, College of Medicine, Inha University, Incheon 22212, Republic of Korea; Hypoxia-related Disease Research Center, College of Medicine, Inha University, Incheon 22212, Republic of Korea. Electronic address: park001@inha.ac.kr.

Abstract

Hypoxia leads to cancer progression and promotes the metastatic potential of cancer cells. MicroRNAs (miRNAs) are small non-coding RNA that have emerged as key players involved in cancer development and progression. Hypoxia alters a set of hypoxia-mediated miRNAs expression during tumor development and it may function as oncogenes or tumor-suppressors. However, the roles and molecular mechanisms of hypoxia-regulatory miRNAs in colorectal cancer (CRC) progression remain poorly understood. Here we firstly identified miR-590-5p as hypoxia-sensitive miRNAs which was upregulated in colon cancer cells under hypoxia. Hypoxia-induced miR-590-5p suppressed the expression of RECK, in turn, promoting cell invasiveness and migratory abilities via activation of matrix metalloproteinases (MMPs) and filopodia protrusion in vitro. Inhibition of miR-590-5p suppressed tumor growth and metastasis in mouse xenograft and CRC liver metastasis models via inhibition of MMPs activity. Clinical analysis revealed higher miR-590-5p expression in CRC, compared to normal specimens. Furthermore, miR-590-5p expression was significantly increased in liver metastasis as compared to their matched primary CRC. Taken together, our findings provide the first evidence that miR-590-5p may have potential as a therapeutic target for CRC patients with metastasis.

KEYWORDS:

Colorectal cancer; Hypoxia; Metastasis; Tumor progression; microRNA

PMID:
29247825
DOI:
10.1016/j.canlet.2017.12.018
[Indexed for MEDLINE]

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