miR-144 downregulation increases bladder cancer cell proliferation by targeting EZH2 and regulating Wnt signaling
Autor: | Jun Lin, Feng Qiu, Yichen Zhu, Zhipeng Wang, Ye Tian, Peiqian Yang, Liang Ying, Yu-wen Guo |
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Rok vydání: | 2013 |
Předmět: |
Male
Molecular Sequence Data Primary Cell Culture Urinary Bladder Biology medicine.disease_cause Biochemistry Downregulation and upregulation Cell Line Tumor microRNA medicine Humans Enhancer of Zeste Homolog 2 Protein Wnt Signaling Pathway Molecular Biology beta Catenin Aged Cell Proliferation Aged 80 and over Bladder cancer Base Sequence Cell growth EZH2 Polycomb Repressive Complex 2 Wnt signaling pathway Cancer Cell Biology Middle Aged medicine.disease Cell biology Gene Expression Regulation Neoplastic Wnt Proteins MicroRNAs Urinary Bladder Neoplasms Cancer research Female Urothelium Carcinogenesis Protein Binding |
Zdroj: | FEBS Journal. 280:4531-4538 |
ISSN: | 1742-464X |
DOI: | 10.1111/febs.12417 |
Popis: | microRNAs (miRNAs) have been proposed to be key regulators of diverse biological processes such as transcriptional regulation, cell growth and tumorigenesis. Wnt signaling plays an important role in the regulation of tumorigenesis and cancer progression. However, little is known about whether miR-144 regulates bladder cancer cell proliferation by controlling Wnt signaling. In this study, we found that the miR-144 expression level is significantly decreased in bladder cancer cell lines as well as in clinical cancer tissues. miR-144 inhibitor blocks the expression of endogenous miR-144 and promotes cancer cell proliferation, whereas miR-144 overexpression is sufficient to inhibit cell proliferation. We further demonstrated that enhancer of zeste homolog 2 (EZH2) is a target gene of miR-144. miR-144 downregulation relieves miR-144-mediated repression of EZH2, which results in activation of Wnt/β-catenin signaling and subsequent cell proliferation. These data suggest miR-144 is an essential mediator of bladder cancer cell proliferation, thus offering a new target for the development of therapeutic agents against bladder cancer. |
Databáze: | OpenAIRE |
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