| Autor: |
Yuan-yuan Lu, Yi Li, Zhi-li Chen, Xiang-hua Xiong, Qing-yang Wang, Hao-long Dong, Chen Zhu, Jia-zhen Cui, Ao Hu, Lei Wang, Na Song, Gang Liu, Hui-peng Chen |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Molecular and Cellular Probes, Vol 77, Iss , Pp 101981- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
0890-8508 |
| DOI: |
10.1016/j.mcp.2024.101981 |
| Popis: |
The clinical treatment of hepatocellular carcinoma (HCC) is still a heavy burden worldwide. Intracellular microRNAs (miRNAs) commonly express abnormally in cancers, thus they are potential therapeutic targets for cancer treatment. miR-21 is upregulated in HCC whereas miR-122 is enriched in normal hepatocyte but downregulated in HCC. In our study, we first generated a reporter genetic switch compromising of miR-21 and miR-122 sponges as sensor, green fluorescent protein (GFP) as reporter gene and L7Ae:K-turn as regulatory element. The reporter expression was turned up in miR-21 enriched environment while turned down in miR-122 enriched environment, indicating that the reporter switch is able to respond distinctly to different miRNA environment. Furthermore, an AAT promoter, which is hepatocyte-specific, is applied to increase the specificity to hepatocyte. A killing switch with AAT promoter and an apoptosis-inducing element, Bax, in addition to miR-21 and miR-122 significantly inhibited cell viability in Huh-7 by 70 % and in HepG2 by 60 %. By contrast, cell viability was not affected in five non-HCC cells. Thus, we provide a novel feasible strategy to improve the safety of miRNA-based therapeutic agent to cancer. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
Full Text from ScienceDirect