miR-224 targets BTRC and promotes cell migration and invasion in colorectal cancer
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ORIGINAL ARTICLE
miR‑224 targets BTRCand promotes cell migration and invasion in colorectal cancer Qi Zheng1 · Jane J. Yu2 · Chenggang Li3 · Jiali Li4 · Jiping Wang5 · Shuyang Wang1 Received: 6 May 2020 / Accepted: 12 October 2020 © The Author(s) 2020
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 miR224 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 BTRCexpression 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. Keywords miR-224 · MicroRNA · Colorectal cancer · CRC · BTRC · Beta-TrCP
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. Nevertheless, there are still few biomarkers or treatment targets for high-risk early-stage CRC patients who are prone to metastasize, and Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13205-020-02477-x) contains supplementary material, which is available to authorized users. * Shuyang Wang [email protected] 1
Department of Pathology, School of Basic Medical Sciences, Fudan University, 131 Dong’an Road, Shanghai 200032, Shanghai, China
2
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
3
State Key Laboratory of Medical Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China
4
Department of Pathology, Huashan Hospital, Fudan University, Shanghai, China
5
Division of Surgical Oncology, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
the mechanism of metastasis during the early stage of CRC is still unclear. MicroRNAs (miRNAs) are single-strand small noncoding RNAs consisting of 19–25 nucleotides, which usually imperfectly bind to the seed regions within the 3′UTR of complementary target mRNAs resulting in translational repression or mRNA cleavage (Bartel 2004). The dysregulation of most miRNAs has been reported in a wide range of human cancer types (Iorio and Croce 2012). Congruently, many miRNAs are located in chromosomal regions that are prone to deleti
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