A circular RNA circ-DNMT1 enhances breast cancer progression by activating autophagy
| Autor: | Faryal Mehwish Awan, Jian Ma, Sergey N. Krylov, Chunqi Gao, Nan Wu, Chengyan He, Yaou Zhang, Chun Peng, Steven Hibberd, Xiangmin Li, Jun Dong, Weining Yang, Chao Zhang, Juanjuan Lyu, Ling Fang, Mouna Sdiri, Burton B. Yang, Yizhen Xie, Feiya Li, Zhenguo Yang, William W. Du |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
DNA (Cytosine-5-)-Methyltransferase 1 Cancer Research Active Transport Cell Nucleus Mice Nude Breast Neoplasms Biology environment and public health 03 medical and health sciences Mice 0302 clinical medicine Transcription (biology) Circular RNA Cell Line Tumor Genetics medicine Autophagy Gene silencing Animals Humans Heterogeneous Nuclear Ribonucleoprotein D0 Heterogeneous-Nuclear Ribonucleoprotein D Molecular Biology Cellular Senescence urogenital system Cell growth RNA RNA Circular Xenograft Model Antitumor Assays Cell biology Cell nucleus 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis embryonic structures DNMT1 Disease Progression Female Tumor Suppressor Protein p53 |
| Zdroj: | Oncogene. 37(44) |
| ISSN: | 1476-5594 |
| Popis: | Circular RNAs are a large group of noncoding RNAs that are widely expressed in mammalian cells. Genome-wide analyses have revealed abundant and evolutionarily conserved circular RNAs across species, which suggest specific physiological roles of these species. Using a microarray approach, we detected increased expression of a circular RNA circ-Dnmt1 in eight breast cancer cell lines and in patients with breast carcinoma. Silencing circ-Dnmt1 inhibited cell proliferation and survival. Ectopic circ-Dnmt1 increased the proliferative and survival capacities of breast cancer cells by stimulating cellular autophagy. We found that circ-Dnmt1-mediated autophagy was essential in inhibiting cellular senescence and increasing tumor xenograft growth. We further found that ectopically expressed circ-Dnmt1 could interact with both p53 and AUF1, promoting the nuclear translocation of both proteins. Nuclear translocation of p53 induced cellular autophagy while AUF1 nuclear translocation reduced Dnmt1 mRNA instability, resulting in increased Dnmt1 translation. From here, functional Dnmt1 could then translocate into the nucleus, inhibiting p53 transcription. Computational algorithms revealed that both p53 and AUF1 could bind to different regions of circ-Dnmt1 RNA. Our results showed that the highly expressed circular RNA circ-Dnmt1 could bind to and regulate oncogenic proteins in breast cancer cells. Thus circ-Dnmt1 appears to be an oncogenic circular RNA with potential for further preclinical research. |
| Databáze: | OpenAIRE |
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