Abstract
miRNAs play a crucial part in multiple biological processes of cell proliferation, migration, apoptosis, and chemoresistance. In cancer, miRNAs can be divided into oncogenes or tumor suppressors on the basis of their functions in the carcinogenic process. The purpose of this study was to explore the roles and clinical diagnostic value of miR-370-3p in breast cancer. Our results demonstrated that miR-370-3p significantly promoted proliferation, metastasis, and stemness of breast cancer in vitro and in vivo. In particular, clinical data revealed that high expression of serum miR-370-3p and exosomal miR-370-3p from breast cancer patients was remarkably correlated with lymphatic metastasis and tumor node metastasis (TNM) stages. Mechanistically, miR-370-3p inhibited FBLN5 expression and activated the NF-κB signaling pathway to promote breast cancer cell proliferation, migration, and stemness. FBLN5 expression was significantly decreased in breast cancer cells and tumor tissues of breast cancer patients. Our research identified that miR-370-3p promoted breast cancer progression by inhibiting FBLN5 expression and activating the NF-κB signaling pathway. Serum exosomal miR-370-3p would provide a potential biomarker for the diagnosis of breast cancer.
Highlights
Breast cancer is the most common form of cancer among women
We found that bacterial lipopolysaccharide (LPS) promoted the metastasis of breast cancer cells in vitro and in vivo by activating the TLR4/MyD88/NF-κB signaling pathway
We found that the expression of FBLN5 in breast cancer cells and breast cancer tissues was lower than that in breast epithelial cells and normal breast tissues, which confirmed that the expression level of FBLN5 was negatively correlated with miR-370-3p
Summary
Breast cancer is the most common form of cancer among women. Its incidence rate ranks first in malignant tumors of women [1], and it is the second leading cause of cancer-related death in women [2]. MicroRNAs (miRNAs) have emerged as important roles in the carcinogenesis and progression of breast cancer by regulating target gene expression via posttranscriptional processing [3, 4]. It has been previously reported that miR-128 can target Bcl-2-related x (Bax) gene to promote the proliferation of MCF-7 cells [5]. Metastatic breast cancer cells (MBC) could secrete and transport miR-1246 to mammary epithelial cells and nonmetastatic breast cancer cells to suppress the expression of cyclin-g2, thereby enhancing survival rates and mobility of breast cancer cells [6]
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