miR‑124 inhibits cell growth through targeting IQGAP1 in colorectal cancer

Fan,Jianyu; Zhang,Wenjing; Wu,Yanting; Wan,Ping; Guo,Qiang; Zhang,Yu

doi:10.3892/mmr.2018.9518

miR‑124 inhibits cell growth through targeting IQGAP1 in colorectal cancer

Authors:
- Jianyu Fan
- Wenjing Zhang
- Yanting Wu
- Ping Wan
- Qiang Guo
- Yu Zhang
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Affiliations: Faculty of Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650000, P.R. China, Department of Gastroenterology, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, P.R. China
Published online on: September 27, 2018 https://doi.org/10.3892/mmr.2018.9518
Pages: 5270-5278

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Abstract

MicroRNA (miRNA/miR)-124 is a miRNA, which exerts tumor suppressive effects but is frequently absent in tumors. Although it has been validated to target oncogenic genes such as signal transducer and activator of transcription 3, forkhead box Q1, and Slug, the mechanistic link between miR‑124 and potential target genes that contribute to tumor progression, is yet to be investigated. IQ motif containing GTPase activating protein 1 (IQGAP1) is a scaffold protein that participates in protein‑protein interactions and integrating diverse signaling pathways. Previous studies suggest that overexpression of IQGAP1 enhances activity of mitogen activated protein kinase 1 and β‑catenin signaling cascades to facilitate tumor progression. The present study aimed to identify the regulative link between miR‑124 and IQGAP1 in colorectal cancer (CRC). It was demonstrated that IQGAP1 was aberrantly overexpressed in CRC tissues and cell lines. Knockdown of IQGPA1 by introducing short hairpin‑IQGAP1 lentivirus inhibited CRC cell growth and colony formation ability, and simultaneously suppressed phosphorylation of extracellular signal‑regulated kinase (ERK)1/2 and β‑catenin expression. Furthermore, it was demonstrated that miR‑124 was silenced in CRC. Restoration of miR‑124 in CRC cells impeded cell growth and colony formation ability. The direct binding of miR‑124 to the 3'untranslated region of IQGAP1 mRNA was confirmed using a luciferase reporter gene assay. Importantly, downregulation of IQGAP1 expression was observed in miR‑124‑restoration cells with simultaneous reduction of phosphorylated‑ERK1/2 and β‑catenin. In conclusion, the present study describes a potential mechanism underlying the miR‑124/IQGAP1 link in CRC progression. Silencing of miR‑124 may depress IQGAP1 expression, leading to increased activity of ERK1/2 and β‑catenin signaling.

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