2. Academic Validation
  3. Genetic switch selectively kills hepatocellular carcinoma cell based on microRNA and tissue-specific promoter

Genetic switch selectively kills hepatocellular carcinoma cell based on microRNA and tissue-specific promoter

  • Mol Cell Probes. 2024 Oct:77:101981. doi: 10.1016/j.mcp.2024.101981.
Yuan-Yuan Lu 1,  Yi Li 2,  Zhi-Li Chen 3,  Xiang-Hua Xiong 3,  Qing-Yang Wang 3,  Hao-Long Dong 3,  Chen Zhu 3,  Jia-Zhen Cui 3,  Ao Hu 1,  Lei Wang 4,  Na Song 5,  Gang Liu 6,  Hui-Peng Chen 3
Affiliations

Affiliations

  • 1 Institutes of Physical Science and Information Technology, Anhui University, Hefei, 230000, China; Academy of Military Medical Sciences, Beijing, 100850, China.
  • 2 Academy of Military Medical Sciences, Beijing, 100850, China; Center for Disease Control and Prevention in Northern Theater Command of the People's Liberation Army, Shenyang, 110031, China.
  • 3 Academy of Military Medical Sciences, Beijing, 100850, China.
  • 4 Department of Orthopedic Surgery, Senior Department of Orthopedics, The Fourth Medical Center of PLA General Hospital, Beijing, 100048, China. Electronic address: 307_wl@163.com.
  • 5 Department of Critical Care Medicine, People's Hospital of Laoling, Laoling, 253600, China.
  • 6 Academy of Military Medical Sciences, Beijing, 100850, China. Electronic address: liug@bmi.ac.cn.
PMID: 39197503 DOI: 10.1016/j.mcp.2024.101981
Abstract

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.

Keywords

Genetic switch; Hepatocellular carcinoma cell; Hepatocyte-specific promoter; microRNA.

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