Long noncoding RNA MEG3 suppresses liver cancer cells growth through inhibiting β-catenin by activating PKM2 and inactivating PTEN
| Autor: | Hu Pu, Dongdong Lu, Yanan Lu, Jie Xu, Chen Wang, Qidi Zheng, Qiuyu Meng, Zhuojia Lin, Tianming Li, Xiaonan Li, Yuxin Yang, Xiaoru Xin, Wujun Xiong, Xin Gui |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Cancer Research Proteasome Endopeptidase Complex Thyroid Hormones Immunology Mice Nude PKM2 Gene Expression Regulation Enzymologic Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Cell Line Tumor Enzyme Stability medicine PTEN Animals Humans lcsh:QH573-671 beta Catenin Cell Proliferation MEG3 Regulation of gene expression Mice Inbred BALB C biology Chemistry Cell growth lcsh:Cytology Liver Neoplasms PTEN Phosphohydrolase Membrane Proteins Cell Biology medicine.disease Tumor Burden Gene Expression Regulation Neoplastic 030104 developmental biology 030220 oncology & carcinogenesis Catenin Proteolysis Cancer research biology.protein RNA Long Noncoding Signal transduction Liver cancer Carrier Proteins Signal Transduction |
| Zdroj: | Cell Death and Disease, Vol 9, Iss 3, Pp 1-18 (2018) Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-018-0305-7 |
| Popis: | Maternally expressed gene 3 (MEG3) encodes an lncRNA which is suggested to function as a tumor suppressor and has been showed to involve in a variety of cancers. Herein, our findings demonstrate that MEG3 inhibits the malignant progression of liver cancer cells in vitro and in vivo. Mechanistically, MEG3 promotes the expression and maturition of miR122 which targets PKM2. Therefore, MEG3 decreases the expression and nuclear location of PKM2 dependent on miR122. Furthermore, MEG3 also inhibits CyclinD1 and C-Myc via PKM2 in liver cancer cells. On the other hand, MEG3 promotes β-catenin degradation through ubiquitin–proteasome system dependent on PTEN. Strikingly, MEG3 inhibits β-catenin activity through PKM2 reduction and PTEN increase. Significantly, we also found that excessive β-catenin abrogated the effect of MEG3 in liver cancer. In conclusion, our study for the first time demonstrates that MEG3 acts as a tumor suppressor by negatively regulating the activity of the PKM2 and β-catenin signaling pathway in hepatocarcinogenesis and could provide potential therapeutic targets for the treatment of liver cancer. |
| Databáze: | OpenAIRE |
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