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RNA-binding protein SAMD4A inhibits breast tumor angiogenesis by modulating the balance of angiogenesis program.
- Source :
-
Cancer science [Cancer Sci] 2021 Sep; Vol. 112 (9), pp. 3835-3845. Date of Electronic Publication: 2021 Jul 16. - Publication Year :
- 2021
-
Abstract
- Tumor-induced angiogenesis is important for further progression of solid tumors. The initiation of tumor angiogenesis is dictated by a shift in the balance between proangiogenic and antiangiogenic gene expression programs. However, the potential mechanism controlling the expression of angiogenesis-related genes in the tumor cells, especially the process mediated by RNA-binding protein (RBP) remains unclear. SAMD4A is a conserved RBP across fly to mammals, and is believed to play an important role in controlling gene translation and stability. In this study, we identified the potential role of SAMD4A in modulating angiogenesis-related gene expression and tumor progression in breast cancer. SAMD4A expression was repressed in breast cancer tissues and cells and low SAMD4A expression in human breast tumor samples was strongly associated with poor survival of patients. Overexpression of SAMD4A inhibited breast tumor angiogenesis and caner progression, whereas knockdown of SAMD4A demonstrated a reversed effect. Mechanistically, SAMD4A was found to specifically destabilize the proangiogenic gene transcripts, including C-X-C motif chemokine ligand 5 (CXCL5), endoglin (ENG), interleukin 1β (IL1β), and angiopoietin 1 (ANGPT1), by directly interacting with the stem-loop structure in the 3' untranslated region (3'UTR) of these mRNAs through its sterile alpha motif (SAM) domain, resulting in the imbalance of angiogenic genes expression. Collectively, our results suggest that SAMD4A is a novel breast tumor suppressor that inhibits tumor angiogenesis by specifically downregulating the expression of proangiogenic genes, which might be a potential antiangiogenic target for breast cancer therapy.<br /> (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Subjects :
- Animals
Disease Progression
Female
HEK293 Cells
Humans
MCF-7 Cells
Mammary Glands, Human cytology
Mice
Mice, Inbred BALB C
Mice, Nude
RNA-Binding Proteins genetics
Repressor Proteins genetics
Transfection
Tumor Burden genetics
Tumor Suppressor Proteins genetics
Xenograft Model Antitumor Assays
Breast Neoplasms blood supply
Gene Expression Regulation, Neoplastic
Neovascularization, Pathologic genetics
Neovascularization, Pathologic metabolism
RNA-Binding Proteins metabolism
Repressor Proteins metabolism
Tumor Suppressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1349-7006
- Volume :
- 112
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cancer science
- Publication Type :
- Academic Journal
- Accession number :
- 34219323
- Full Text :
- https://doi.org/10.1111/cas.15053