HER2-intronic miR-4728-5p facilitates HER2 expression and accelerates cell proliferation and migration by targeting EBP1 in breast cancer
Autor: | Chunyu Liu, Zhen Zhou, Yimin Quan, Xiangfeng Meng, Yuan Yuan, Chen-Yu Zhang, Yu Zhou, Mengchao Yu, Liuyi Li, Chen Wang, Xueliang Wang, Xiuting Hu, Minghui Liu, Xi Chen |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Carcinogenesis Receptor ErbB-2 Kaplan-Meier Estimate medicine.disease_cause Biochemistry 0302 clinical medicine Cell Movement Breast Tumors Medicine and Health Sciences skin and connective tissue diseases Multidisciplinary Luciferase Assay RNA-Binding Proteins Transfection Cancer Cell Migration Enzymes Nucleic acids Cell Motility Bioassays and Physiological Analysis Oncology Cell Processes 030220 oncology & carcinogenesis MCF-7 Cells Medicine Cell lines Biological cultures Oxidoreductases Luciferase Research Article Science Down-Regulation Breast Neoplasms BT474 cells Cell Migration Biology 03 medical and health sciences Breast cancer Downregulation and upregulation Cell Line Tumor Breast Cancer microRNA Genetics medicine Humans Non-coding RNA Adaptor Proteins Signal Transducing Cell Proliferation Enzyme Assays Natural antisense transcripts Cell growth Three prime untranslated region Cancers and Neoplasms Biology and Life Sciences Proteins Cancer Cell Biology medicine.disease Introns Gene regulation Research and analysis methods MicroRNAs 030104 developmental biology Enzymology Cancer research RNA Gene expression Biochemical Analysis Developmental Biology |
Zdroj: | PLoS ONE PLoS ONE, Vol 16, Iss 2, p e0245832 (2021) |
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: | OpenAIRE |
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