4.2 Article

miR-142-3p Suppresses Cell Growth by Targeting CDK4 in Colorectal Cancer

Journal

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 51, Issue 4, Pages 1969-1981

Publisher

KARGER
DOI: 10.1159/000495721

Keywords

Colorectal cancer; miR-142-3p; CDK4; Cell cycle

Funding

  1. National Natural Science Fund from the National Natural Science Foundation of China [81402367]
  2. Clinical Capability Construction Project for Liaoning Provincial Hospitals [LNCCC-D44-2015]
  3. Liaoning BaiQianWan Talents Program [B44]
  4. Liaoning clinical research center for colorectal cancer [2015225005]

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Background/Aims: Deregulation of microRNAs (miRNAs) has been associated with a variety of cancers, including colorectal cancer (CRC). Here, we investigated anomalous miR-142-3p expression and its possible functional consequences in primary CRC samples. Methods: The expression of miR-142-3p was measured by quantitative RT-PCR in 116 primary CRC tissues and adjacent non-tumor tissues. The effect of miR-142-3p up-or down-regulation in CRC-derived cells was evaluated in vitro by cell viability and colony formation assays and in vivo by growth assays in xenografted nude mice. Results: Using quantitative RT-PCR, we found that miR-142-3p was down-regulated in 78.4 % (91/116) of the primary CRC tissues tested when compared to the adjacent non-tumor tissues. We also found that the miR-142-3p mimic reduced in vitro cell viability and colony formation by inducing cell cycle arrest in CRC-derived cells, and inhibited in vivo tumor cell growth in xenografted nude mice. Inversely, we found that the miR-142-3p inhibitor increased the viability and colony forming capacity of CRC-derived cells and tumor cell growth in xenografted nude mice. In addition, we identified CDK4 as a potential target of miR-142-3p by predictions and dual-luciferase reporter assays. Concordantly, we found that miR-142-3p mimics and inhibitors could decrease and increase CDK4 protein levels in CRC-derived cells, respectively. Conclusion: From our results we conclude that miR-142-3p may act as a tumor suppressor in CRC and may serve as a tool for miRNA-based CRC therapy. (C) 2018 The Author(s) Published by S. Karger AG, Basel

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