miR-375 inhibits the invasion and metastasis of colorectal cancer via targeting SP1 and regulating EMT-associated genes

Cui,Fengyun; Wang,Shuyang; Lao,Iweng; Zhou,Chunxian; Kong,Hui; Bayaxi,Nayima; Li,Jiali; Chen,Qi; Zhu,Tengfang; Zhu,Hongguang

doi:10.3892/or.2016.4834

miR-375 inhibits the invasion and metastasis of colorectal cancer via targeting SP1 and regulating EMT-associated genes

Authors:
- Fengyun Cui
- Shuyang Wang
- Iweng Lao
- Chunxian Zhou
- Hui Kong
- Nayima Bayaxi
- Jiali Li
- Qi Chen
- Tengfang Zhu
- Hongguang Zhu
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Affiliations: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, P.R. China
Published online on: May 24, 2016 https://doi.org/10.3892/or.2016.4834
Pages: 487-493

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Abstract

Accumulating evidence has shown that aberrantly expressed microRNAs (miRNAs) are associated with tumor development and progression. Our previous study found that microRNA-375 (miR-375) was downregulated in colorectal cancer (CRC), but little is known concerning the role of miR-375 and the related mechanism in CRC development. The proliferation, invasion and migration effects were investigated by Cell Counting Kit-8 (CCK-8), colony formation and Transwell assays with or without Matrigel. In addition, candidate target genes were screened and validated by luciferase reporter and western blot assays. In addition, western blot analysis was performed to explore the molecular mechanisms associated with epithelial‑mesenchymal transition (EMT). It was found that miR-375 inhibited proliferation, invasion and migration in DLD1 and HCT8 cells. In addition, miR-375 negatively regulated Sp1 transcription factor (SP1) protein by directly binding to the 3'-untranslated region (3'-UTR). Furthermore, it was found that miR-375 regulated matrix metalloproteinase 2 (MMP2) and EMT-associated genes, E-cadherin, vimentin, snail, N-cadherin and β-catenin. In conclusion, miR-375 inhibited the proliferation, invasion and migration by directly targeting SP1 and regulating MMP2 and EMT-associated genes.

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