Mmu-miR-1894-3p Inhibits Cell Proliferation and Migration of Breast Cancer Cells by Targeting Trim46.

Li Zhang,Deyu Guo,Lianfeng Zhang,Wei Dong,Xiaoying Li,Caixian Sun

doi:10.3390/ijms17040609

Abstract

Breast cancer is the second leading cause of cancer death in women and the presence of metastasis significantly decreases survival. MicroRNAs are involved in tumor progression and the metastatic spreading of breast cancer. Here, we reported that a microRNA, mmu-miR-1894, significantly decreased the lung metastasis of 4TO7 mouse breast cancer cells by 86.7% in mouse models. Mmu-miR-1894-3p was the functional mature form of miR-1894 and significantly decreased the lung metastasis of 4TO7 cells by 90.8% in mouse models. A dual-luciferase reporter assay indicated that mmu-miR-1894-3p directly targeted the tripartite motif containing 46 (Trim46) 3′-untranslated region (UTR) and downregulated the expression of Trim46 in 4TO7 cells. Consistent with the effect of mmu-miR-1894-3p, knockdown of Trim46 inhibited the experimental lung metastasis of 4TO7 cells. Moreover, knockdown of human Trim46 also prohibited the cell proliferation, migration and wound healing of MBA-MD-231 human breast cancer cells. These results suggested that the effect of knockdown of Trim46 alone was sufficient to recapitulate the effect of mmu-miR-1894 on the metastasis of the breast cancer cells in mouse and that Trim46 was involved in the proliferation and migration of mouse and human breast cancer cells.

Highlights

Breast cancer is the second leading cause of cancer death in women worldwide, with 232,670 new cases and 40,000 breast cancer deaths annually [1]
We showed that three of the fifteen microRNAs, mmu-mir-449a, mmu-mir-1935 and mmu-mir-1894, had significant effects on lung metastasis of cancer cells
Mmu-mir-449a has been shown as a tumor suppressor in endometrial cancer [16,19], gastric carcinoma [15], lung cancer [17,32], ovarian cancer [33], prostate cancer [18], etc

Summary

Introduction

Breast cancer is the second leading cause of cancer death in women worldwide, with 232,670 new cases and 40,000 breast cancer deaths annually [1]. Cancer metastasis has a strong influence on the length of survival. MicroRNAs (miRNAs) are non-coding RNAs with gene expression regulatory functions, whose de-regulation has been documented in almost all types of human cancer, with respect to the non-tumoral tissue counterpart. MiRNAs can function either as oncogenes or tumor suppressors in mammary tumor progression and tumor metastasis [3,4,5,6,7]. The latest version of miRbase (ver.21) reports included 1881 human miRNA sequences and 1193 mouse miRNA sequences (http://www.mirbase.org) [8]. Previous studies frequently used xenogeneic mouse models of transplanted human cancer cells into immunosuppressed mice to explore the role of human miRNA and their targets in breast cancer metastasis [9]. Mxpoel.rSicmi. e20n1t6a,l1t7u, 6m09or histology and growth rate and, most importantly, the full immunoreactiv2itoyf o12f the host [9,10]

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Conclusion