Author:
Zhou Yu,Yuan Yuan,Li Liuyi,Wang Xueliang,Quan Yimin,Liu Chunyu,Yu Mengchao,Hu Xiuting,Meng Xiangfeng,Zhou Zhen,Zhang Chen-Yu,Chen Xi,Liu Minghui,Wang Chen
Abstract
HER2 amplification greatly contributes to the tumorigenesis of multiple cancers. Intronic miR-4728-5p is transcribed along with its host gene HER2. However, little is known about the role of miR-4728-5p in cancer. This study aims to elucidate the potential role of miR-4728-5p and the underlying mechanism in breast cancer. Kaplan-Meier analysis showed that higher expression of HER2 led to worse survival outcomes in breast cancer patients. The TCGA dataset revealed that compared to normal breast tissues, HER2 and miR-4728-5p levels were significantly upregulated in breast cancer tissues with a positive correlation. In functional assays, miR-4728-5p was confirmed to promote the proliferation and migration in breast cancer cell BT474. EBP1 was identified as a direct target of miR-4728-5p via bioinformatics and luciferase reporter assays. miR-4728-5p was further demonstrated to increase HER2 expression and promote cell proliferation and migration by directly inhibiting EBP1 in breast cancer. Taken together, the HER2-intronic miR-4728-5p/EBP1/HER2 feedback loop plays an important role in promoting breast cancer cell proliferation and migration. Our study provides novel insights for targeted therapies of breast cancer.
Funder
the Chinese Science and Technology Major Project of China
the China Postdoctoral Science Foundation
the National Natural Science Foundation of China
Publisher
Public Library of Science (PLoS)
Cited by
6 articles.
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