MiR-224 targets BTRC and promotes cell migration and invasion in colorectal cancer

Qi Zheng,Shuyang Wang,Jiali Li,Jane J Yu,Chenggang Li,Jiping Wang

doi:10.1007/s13205-020-02477-x

Abstract

Our study aims to investigate the impact of miR-224 on cell migration and invasion in colorectal cancer (CRC) as well as its molecular mechanisms. The results showed that miR-224 was significantly upregulated in CRC compared to normal tissues via the TCGA database. Overexpression of miR-224 promoted CRC cell migration and invasion, while inhibition of miR-224 demonstrated the opposite result via transwell assays. In addition, we found that BTRC was a target gene of miR-224 through the miRecords database and dual-luciferase assay, while western blot together with RT-qPCR showed that inhibition of miR-224 led to elevated BTRC expression in protein level but not in mRNA level, and also decreased the expression of β-catenin. In reference to the Human Protein Atlas, BTRC protein expression was higher in normal tissues than in CRC tissues. In conclusion, miR-224 regulates its target BTRC protein expression and its related Wnt/β-catenin pathway. Its impact on cell migration and invasion in CRC cells suggested that miR-224 could be a prospective therapeutic target for early-stage non-metastatic CRC.

Highlights

Colorectal cancer (CRC) is one of the most common malignant neoplasms in the world (Bray et al 2018) and metastasis is one of its leading causes of death
We report that elevated miR-224 expression level is found in CRC tissues and cell lines and inhibition of miR-224 could upregulate the protein expression of targeted Beta-Transducin Repeat Containing E3 Ubiquitin Protein Ligase (BTRC), suppress the Wnt/β-catenin pathway, and reduce the migratory and invasive abilities of CRC cells
The protein expression, but not transcripts, of BTRCwas downregulated in CRC tissues compared to normal tissues based on TCGA and the IHC data from the Human Protein Atlas

Summary

Introduction

Colorectal cancer (CRC) is one of the most common malignant neoplasms in the world (Bray et al 2018) and metastasis is one of its leading causes of death. Many miRNAs are located in chromosomal regions that are prone to deletions or amplifications in the development of many different types of cancer (Calin et al 2004). The amplification of those regions containing onco-miR would increase miRNA expression and silence targeted tumor suppressor genes. MiRNAs involved in the suppression of oncogenes are often located in the fragile loci where deletions or mutations tend to occur, leading to decreased miRNA levels and overexpression of the targeted oncogenes (Iorio and Croce 2012)

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Conclusion