miR‐188‐5p suppresses cellular proliferation and migration via IL6ST: A potential noninvasive diagnostic biomarker for breast cancer

• Published in: Journal of cellular physiology Vol. 235; no. 5; pp. 4890 - 4901
• Main Authors: Wang, Mei, Zhang, Huiling, Yang, Fang, Qiu, Rong, Zhao, Xinxin, Gong, Zheng, Yu, Wanjun, Zhou, Baocheng, Shen, Bo, Zhu, Wei
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.05.2020
• Subjects: Biomarkers; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biopsy; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Case-Control Studies; Cell migration; Cell Movement; Cell Proliferation; Circulating MicroRNA - blood; Circulating MicroRNA - genetics; Cytokine Receptor gp130 - genetics; Cytokine Receptor gp130 - metabolism; Diagnostic systems; Exosomes; Exosomes - genetics; Exosomes - metabolism; Exosomes - pathology; Female; Fibroadenoma; Fibroadenoma - blood; Fibroadenoma - genetics; Gene Expression Regulation, Neoplastic; Humans; IL6ST; Interleukin 6; Lymph nodes; MCF-7 Cells; Metastases; MicroRNAs - blood; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR‐188‐5p; Neoplasm Invasiveness; Polymerase chain reaction; Predictive Value of Tests; Prognosis; Regulatory mechanisms (biology); serum; Signal Transduction; Therapeutic applications; tumor suppressor; Tumor Suppressor Proteins - blood; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; breast cancer; tumor suppressor; miR-188-5p; IL6ST; serum
• DOI: 10.1002/jcp.29367
• ISSN: 0021-9541; 1097-4652

Previously, serum miR‐188‐5p is differentially expressed in breast cancer, but the diagnostic potential of circulating miR‐188‐5p as well as its regulatory mechanism in breast cancer remain uncertain. Herein, serum miR‐188‐5p was detected by real‐time polymerase chain reaction in patients with breast cancer, breast fibroadenoma, and healthy subjects. Circulating miR‐188‐5p was abnormally elevated in patients with breast cancer as compared with these other two groups, and was reduced in patients with breast cancer following surgical treatment. Increased serum miR‐188‐5p corresponded to lymph node metastasis status and TNM stages of breast cancer. A receiver operating characteristic curve analysis of the ability to circulate miR‐188‐5p to distinguish between patients with breast cancer and either noncancerous patients or patients with breast fibroadenoma yielded corresponding areas under the curve of 0.894 and 8.814. miR‐188‐5p was downregulated in the highly malignant cancer line MDA‐MB‐231 relative to the less malignant MCF‐7 cells. In vitro, functional analyses conducted via transfecting cells with mimics and inhibitors revealed miR‐188‐5p to suppress breast cancer cell proliferation and migration, which was mediated by its downstream target IL6ST. Comparison of intracellular and exosomal miR‐188‐5p levels indicated that miR‐188‐5p was selectively sorted into exosomes derived from MDA‐MB‐231 cells rather than those from MCF‐7 cells. However, exosomal miR‐188‐5p levels in the serum of patients with breast cancer were reduced compared to healthy controls and did not differ relative to patients with breast fibroadenoma. In summary, miR‐188‐5p acts in a tumor‐suppressive manner in breast cancer progression and may serve as a noninvasive early diagnostic biomarker and therapeutic target in breast cancer. Previously, serum miR‐188‐5p is differentially expressed in breast cancer, but the diagnostic potential of circulating miR‐188‐5p as well as its regulatory mechanism in breast cancer remain uncertain. Herein, circulating miR‐188‐5p was found to be increased in patients with breast cancer, exhibit high diagnostic accuracy in discriminating patients with breast fibroadenoma and healthy subjects, suppress breast cancer cell proliferation and migration via regulation of its target IL6ST, and to be selectively sorted into cancer cell‐derived exosomes, which suggest that miR‐188‐5p acts in a tumor‐suppressive manner in breast cancer progression, and may serve as a noninvasive early diagnostic biomarker and therapeutic target in breast cancer.