A tRNA fragment, 5'-tiRNAVal, suppresses the Wnt/β-catenin signaling pathway by targeting FZD3 in breast cancer.

Abstract

tRNA-derived fragments offer a recently identified group of non-coding single-stranded RNAs that are often as abundant as microRNAs in cancer cells and play important roles in carcinogenesis. However, the biological functions of them in breast cancer are still unclear. Hence, we focused on investigating whether tiRNAs could play a key role in the progression of breast cancer. We have identified 5'-tiRNAVal with significantly low expression in breast cancer tissues. The down-regulation of serum 5'-tiRNAVal was positively correlated with stage progression and lymph node metastasis. Overexpression of 5'-tiRNAVal suppressed cells malignant activities. FZD3 was confirmed to be a direct target of 5'-tiRNAVal in breast cancer. In addition, FZD3, β-Catenin, c-myc and cyclinD1 levels in 5'-tiRNAVal overexpressing cells were downregulated while APC was inversely upregulated. Moreover, 5'-tiRNAVal inhibited the FZD3-mediated Wnt/β-Catenin signaling pathway in breast cancer cells. Finally, 5'-tiRNAVal levels differentiated breast cancer from healthy controls with a sensitivity of 90.0% and specificity of 62.7%. This is the first study to show that 5'-tiRNAVal as a new tumor-suppressor through inhibition of FZD3/Wnt/β-Catenin signaling pathway, which could be as a potential diagnostic biomarker for breast cancer.

• Authors: Dongping Mo, Pan Jiang, Yining Yang, Xuelian Mao, Xuyan Tan, Xun Tang, Da Wei, Bing Li, Xiaoming Wang, Li Tang, Feng Yan
• Journal: Cancer letters (Cancer Lett) Vol. 457 Pg. 60-73 (08 10 2019) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 31078732 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• CCND1 protein, human
• CTNNB1 protein, human
• FZD3 protein, human
• Frizzled Receptors
• MYC protein, human
• Proto-Oncogene Proteins c-myc
• RNA, Transfer, Val
• beta Catenin
• Cyclin D1

Topics

• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Movement
• Cell Proliferation
• Cyclin D1 (genetics, metabolism)
• Down-Regulation
• Female
• Frizzled Receptors (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Lymphatic Metastasis
• MCF-7 Cells
• Middle Aged
• Neoplasm Staging
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• RNA, Transfer, Val (genetics, metabolism)
• Wnt Signaling Pathway
• beta Catenin (genetics, metabolism)