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J Surg Res. 2019 Aug;240:48-59. doi: 10.1016/j.jss.2019.02.035. Epub 2019 Mar 22.

MicroRNA-7 Exerts Antiangiogenic Effect on Colorectal Cancer via ERK Signaling.

Author information

1
Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Intensive Care Unit, Wuhan NO.1 Hospital, Wuhan, China.
2
Department of Intensive Care Unit, Wuhan NO.1 Hospital, Wuhan, China.
3
Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: 66799073@qq.com.

Abstract

BACKGROUND:

Recent studies have suggested that microRNA-7 (miR-7) family members may play important roles in human cancer by regulating cell proliferation, apoptosis, migration, and invasion. Therefore, the present study aimed to investigate the clinical significance and biological function of miR-7 in colorectal cancer (CRC).

METHODS:

Initially, cancer and adjacent tissues were collected from 76 patients with CRC. Then, microvascular density was detected using the Weidner counting method. The functional role of miR-7 in CRC was determined using ectopic expression, knockdown, and reporter assay experiments. The vasculogenic mimicry density was determined. Expression of miR-7, epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK1/2), vascular endothelial growth factor, and thrombospondin-1 was determined. 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assays, scratch tests, and Transwell assays were conducted to examine cell proliferation, migration, and invasion, respectively. Finally, flow cytometry was applied to evaluate cell apoptosis.

RESULTS:

CRC tissues showed increased microvascular density and EGFR expression, activated ERK signaling, and miR-7 downregulation. EGFR was a target gene of miR-7. miR-7 overexpression and EGFR silencing decreased vasculogenic mimicry density, cell migration, and cell invasion, but increased cell apoptosis. In addition, miR-7 overexpression and EGFR silencing upregulated thrombospondin-1 and downregulated EGFR, ERK1/2, and vascular endothelial growth factor. Furthermore, we observed that the effect of miR-7 inhibition was abolished after EGFR silencing.

CONCLUSIONS:

Overexpressed miR-7 suppresses angiogenesis of CRC cells through ERK signaling by downregulating EGFR. It may identify new targets for CRC treatment.

KEYWORDS:

Angiogenesis; Colorectal cancer; ERK signaling; Epidermal growth factor receptor; MicroRNA-7

PMID:
30909065
DOI:
10.1016/j.jss.2019.02.035

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