The MicroRNA-23b/27b/24 Cluster Facilitates Colon Cancer Cell Migration by Targeting FOXP2

Acquisition of cell migration capacity is an early and essential process in cancer development. The aim of this study was to identify microRNA gene expression networks that induced high migration capacity. Using colon cancer HCT116 cells subcloned by transwell-based migrated cell selection, microRNA...

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Main Authors: Kensei Nishida, Yuki Kuwano, Kazuhito Rokutan
Format: Article
Language:English
Published: MDPI AG 2020-01-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/12/1/174
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author Kensei Nishida
Yuki Kuwano
Kazuhito Rokutan
author_facet Kensei Nishida
Yuki Kuwano
Kazuhito Rokutan
author_sort Kensei Nishida
collection DOAJ
description Acquisition of cell migration capacity is an early and essential process in cancer development. The aim of this study was to identify microRNA gene expression networks that induced high migration capacity. Using colon cancer HCT116 cells subcloned by transwell-based migrated cell selection, microRNA array analysis was performed to examine the microRNA expression profile. Promoter activity and microRNA targets were assessed with luciferase reporters. Cell migration capacity was assessed by either the transwell or scratch assay. In isolated subpopulations with high migration capacity, the expression levels of the <i>miR-23b/27b/24</i> cluster increased in accordance with the increased expression of the short <i>C9orf3</i> transcript, a host gene of the <i>miR-23b/27b/24</i> cluster. E2F1-binding sequences were involved in the basic transcription activity of the short <i>C9orf3</i> expression, and E2F1-small-interfering (si)RNA treatment reduced the expression of both the <i>C9orf3</i> and <i>miR-23b/27b/24</i> clusters. Overexpression experiments showed that <i>miR-23b</i> and <i>miR-27b</i> promoted cell migration, but the opposite effect was observed with <i>miR-24</i>. Forkhead box P2 (FOXP2) mRNA and protein levels were reduced by both/either <i>miR-23b</i> and <i>miR-27b</i>. Furthermore, FOXP2 siRNA treatment significantly promoted cell migration. Our findings demonstrated a novel role of the <i>miR-23b/27b/24</i> cluster in cell migration through targeting FOXP2, with potential implications for the development of microRNA-based therapy targeted at inhibiting cancer migration.
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spelling doaj.art-e2aece2e7472415785b093ef0d4475022023-09-03T04:53:20ZengMDPI AGCancers2072-66942020-01-0112117410.3390/cancers12010174cancers12010174The MicroRNA-23b/27b/24 Cluster Facilitates Colon Cancer Cell Migration by Targeting FOXP2Kensei Nishida0Yuki Kuwano1Kazuhito Rokutan2Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 7708503, JapanDepartment of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 7708503, JapanDepartment of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 7708503, JapanAcquisition of cell migration capacity is an early and essential process in cancer development. The aim of this study was to identify microRNA gene expression networks that induced high migration capacity. Using colon cancer HCT116 cells subcloned by transwell-based migrated cell selection, microRNA array analysis was performed to examine the microRNA expression profile. Promoter activity and microRNA targets were assessed with luciferase reporters. Cell migration capacity was assessed by either the transwell or scratch assay. In isolated subpopulations with high migration capacity, the expression levels of the <i>miR-23b/27b/24</i> cluster increased in accordance with the increased expression of the short <i>C9orf3</i> transcript, a host gene of the <i>miR-23b/27b/24</i> cluster. E2F1-binding sequences were involved in the basic transcription activity of the short <i>C9orf3</i> expression, and E2F1-small-interfering (si)RNA treatment reduced the expression of both the <i>C9orf3</i> and <i>miR-23b/27b/24</i> clusters. Overexpression experiments showed that <i>miR-23b</i> and <i>miR-27b</i> promoted cell migration, but the opposite effect was observed with <i>miR-24</i>. Forkhead box P2 (FOXP2) mRNA and protein levels were reduced by both/either <i>miR-23b</i> and <i>miR-27b</i>. Furthermore, FOXP2 siRNA treatment significantly promoted cell migration. Our findings demonstrated a novel role of the <i>miR-23b/27b/24</i> cluster in cell migration through targeting FOXP2, with potential implications for the development of microRNA-based therapy targeted at inhibiting cancer migration.https://www.mdpi.com/2072-6694/12/1/174cell migration<i>mir-23b/27b/24</i> cluster<i>c9orf3</i>foxp2
spellingShingle Kensei Nishida
Yuki Kuwano
Kazuhito Rokutan
The MicroRNA-23b/27b/24 Cluster Facilitates Colon Cancer Cell Migration by Targeting FOXP2
Cancers
cell migration
<i>mir-23b/27b/24</i> cluster
<i>c9orf3</i>
foxp2
title The MicroRNA-23b/27b/24 Cluster Facilitates Colon Cancer Cell Migration by Targeting FOXP2
title_full The MicroRNA-23b/27b/24 Cluster Facilitates Colon Cancer Cell Migration by Targeting FOXP2
title_fullStr The MicroRNA-23b/27b/24 Cluster Facilitates Colon Cancer Cell Migration by Targeting FOXP2
title_full_unstemmed The MicroRNA-23b/27b/24 Cluster Facilitates Colon Cancer Cell Migration by Targeting FOXP2
title_short The MicroRNA-23b/27b/24 Cluster Facilitates Colon Cancer Cell Migration by Targeting FOXP2
title_sort microrna 23b 27b 24 cluster facilitates colon cancer cell migration by targeting foxp2
topic cell migration
<i>mir-23b/27b/24</i> cluster
<i>c9orf3</i>
foxp2
url https://www.mdpi.com/2072-6694/12/1/174
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