HER2-intronic miR-4728-5p facilitates HER2 expression and accelerates cell proliferation and migration by targeting EBP1 in breast cancer.

Autor: Yu Zhou, Yuan Yuan, Liuyi Li, Xueliang Wang, Yimin Quan, Chunyu Liu, Mengchao Yu, Xiuting Hu, Xiangfeng Meng, Zhen Zhou, Chen-Yu Zhang, Xi Chen, Minghui Liu, Chen Wang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: PLoS ONE, Vol 16, Iss 2, p e0245832 (2021)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0245832
Popis: 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.
Databáze: Directory of Open Access Journals
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