MiR-891a-5p as a prognostic marker and therapeutic target for hormone receptor-positive breast cancer

Abstract

Background: Breast cancer is one of the most frequent malignant tumors worldwide, with 1.67 million newly-diagnosed cases and 522,000 deaths each year. Therefore, seeking the novel biomarkers and therapeutic targets that contribute to postoperative recurrence and metastasis in patients with breast cancer is emerging and facilitates the development of innovative therapeutics. Methods: Retrieving the dataset of patients with hormone receptor (HR)-positive breast cancers from Gene Expression Omnibus (GEO) and collecting the data from the patients with HR-positive breast cancers enrolled in the First Affiliated Hospital of China Medical University are so as to identify the miRNAs associated with metastasis and distant metastasis-free survival (DMFS). Then MTT and Transwell migration assays were used to validate the effect of miRNAs on cell proliferation and migration of estrogen receptor-positive breast cancer T47D and MCF7 cells in vitro, respectively. Results: From GSE59829 dataset, the miRNA expression levels of miR-891a-5p, miR-383-5p and miR-1295a were significantly downregulated while the levels of miR-128-3p, miR-661 and miR-296-3p were significantly upregulated in breast cancers from patients with metastasis as compared to the matched non-metastatic group. Moreover, low expression levels of miR-891a-5p, miR-383-5p and miR-1295a or high expression levels of miR-128-3p, miR-661 and miR-296-3p were respectively associated with low DMFS in patients with breast cancer. Our clinical cohort study supported that the levels of miR-891a-5p, miR-383-5p and miR-1295a were significantly lower in breast cancers from the metastasis group when compared with non-metastatic group. However, there is no significant difference with regard to the levels of miR-128-3p, miR-661 and miR-296-3p in breast cancer between these two groups. Moreover, low expression levels of miR-891a-5p and miR-383-5p but not miR-1295a in breast cancer were significantly associated with low DMFS in patients, implying that the expression of miR-891a-5p and miR-383-5p were the potential prognosis markers for metastatic human breast cancers. Further investigation disclosed that miR-891a-5p but not miR-383-5p restrained both proliferation and migration of T47D and MCF7 cells. In silico analysis of miRNAs target gene through online computational algorithms revealed that A Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is the downstream target for miR-891a-5p. Further study confirmed that miR-891a-5p impeded ADAM10 expression by directly binding to its 3'UTR, leading to the inhibition of breast cancer cells proliferation and migration. Moreover, silencing ADAM10 inhibited T47D and MCF7 cells growth and migration. Conclusion: miR-891a-5p is the vital prognostic marker for HR-positive breast cancer. In addition, miR-891a-5p and miR-383-5p are the potential targets for HR-positive breast cancer therapeutics.

MicroRNA‑891a‑5p is a novel biomarker for non‑small cell lung cancer and targets HOXA5 to regulate tumor cell biological function

“…As a functional miRNA, miR-891a-5p has become a hot topic, particularly when investigating tumors, cell proliferation and cell differentiation ( 28 ). Zhang et al found that low expression levels of miR-891a-5p in breast cancer tissue were significantly associated with low distant metastasis-free survival in patients with breast cancer, suggesting that the expression level of miR-891a-5p could be a potential prognostic marker for metastatic human breast cancer ( 29 ). However, the biological function and clinical significance of miR-891a-5p have rarely been reported in NSCLC.…”

miR-383-5p Inhibits Human Malignant Melanoma via Targeting CENPF

“…As an oncogene or tumor suppressor, miRNA provides new regulatory mechanisms (12) based on the biological function of target genes, and can be used for the classi cation and prognosis prediction of cancer (13). According to reports, miR-383-5p acts as a tumor suppressor in a variety of human cancers by modulating multiple target genes (14)(15)(16)(17)(18). Many studies have shown that the expression of miR-383-5p is down-regulated in various human cancer, and the reduction of miR-383-5p is considered a potential biomarker for metastasis and poor prognosis (14)(15)(16)(17)(18).…”

“…According to reports, miR-383-5p acts as a tumor suppressor in a variety of human cancers by modulating multiple target genes (14)(15)(16)(17)(18). Many studies have shown that the expression of miR-383-5p is down-regulated in various human cancer, and the reduction of miR-383-5p is considered a potential biomarker for metastasis and poor prognosis (14)(15)(16)(17)(18). In addition, miR-383-5p inhibits cell proliferation and mobility of various cancer cells, and induces apoptosis (14)(15)(16)(17)(18).…”

“…Many studies have shown that the expression of miR-383-5p is down-regulated in various human cancer, and the reduction of miR-383-5p is considered a potential biomarker for metastasis and poor prognosis (14)(15)(16)(17)(18). In addition, miR-383-5p inhibits cell proliferation and mobility of various cancer cells, and induces apoptosis (14)(15)(16)(17)(18). Furthermore, the over-expression of miR-383-5p enhances the chemosensitivity of ovarian cancer cells (19) and prompts a better response outcome in sorafenib targeting therapy for hepatocellular carcinoma cells (20).…”

The Status of EGFR Modulates the Effect of miRNA-200c on ZEB1 Expression and Cell Migration in Glioblastoma Cells

“…Several studies suggest that some miR-200 family members, including miR-200b and miR-141, are significantly downregulated in glioma tissues, and that this dysregulation correlates with the pathological grade of gliomas [ 42 , 43 ]. Low expression levels of miRNA-891a in breast cancer have been recently associated with low distant metastasis-free survival, implying that the expression of miR-891a-5p is a potential prognosis marker for metastatic human breast cancers [ 44 ]. MiR-892b inhibits proliferation, migration and invasion in bladder cancer cell lines [ 45 ].…”