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miR‐188‐5p suppresses cellular proliferation and migration via IL6ST: A potential noninvasive diagnostic biomarker for breast cancer
Author(s) -
Wang Mei,
Zhang Huiling,
Yang Fang,
Qiu Rong,
Zhao Xinxin,
Gong Zheng,
Yu Wanjun,
Zhou Baocheng,
Shen Bo,
Zhu Wei
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29367
Subject(s) - breast cancer , cancer , fibroadenoma , medicine , biomarker , cancer research , ca 15 3 , ca15 3 , breast fibroadenoma , metastasis , oncology , pathology , biology , biochemistry
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.