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

Autor: Xiangyu Zhu, Si-ping Ma, Dongxiang Yang, Yanlong Liu, Yong-peng Wang, Tao Lin, Yan-xi Li, Shi-hua Yang, Wan-chuan Zhang, Xin-ling Wang
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Cellular Physiology and Biochemistry, Vol 51, Iss 4, Pp 1969-1981 (2018)
Druh dokumentu: article
ISSN: 1015-8987
1421-9778
DOI: 10.1159/000495721
Popis: 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.
Databáze: Directory of Open Access Journals
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