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Updated: May 12, 2025

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
miR-603 mediates thyroid cancer progression by inhibiting HACE1-Dependent YAP1 degradation
Tangya Li1, Jian Chu2, Guangjun Zhou2
1Department of Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China; Department of General Surgery, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, Yancheng, 224005, Jiangsu, China.
Abstract:
This study delineates the regulatory role of MicroRNA-603 (miR-603) on the molecular dynamics of HACE1 and YAP1 in thyroid cancer (TC). Using a combination of bioinformatics, dual-luciferase reporter assays, and various cellular assays, we identified that miR-603 is significantly overexpressed in TC tissues and cells. Our investigations confirmed that miR-603 targets the 3'UTR of HACE1, suppressing its expression, which in turn affects the ubiquitination and stability of the YAP1 protein. Specifically, HACE1's suppression led to decreased YAP1 degradation, promoting cellular processes associated with tumor progression, such as proliferation, migration, and invasion. These in vitro findings were corroborated by in vivo experiments in a TC xenograft model, demonstrating that miR-603 facilitates tumor growth through stabilization of YAP1 protein by targeting HACE1. These results highlight a novel miRNA-mediated pathway influencing TC pathogenesis and suggest potential targets for therapeutic intervention.
Insights
MicroRNA-603 (miR-603) is overexpressed in thyroid cancer (TC), promoting tumor growth by targeting HACE1. This mechanism stabilizes YAP1 protein, driving cancer progression and suggesting new therapeutic strategies.
Area of Science:
- Molecular biology
- Oncology
- Biochemistry
Background:
- Thyroid cancer (TC) pathogenesis involves complex molecular dysregulation.
- MicroRNAs (miRNAs) play critical roles in cancer development and progression.
- Understanding novel regulatory pathways is crucial for identifying therapeutic targets.
Purpose of the Study:
- To investigate the regulatory role of MicroRNA-603 (miR-603) in thyroid cancer.
- To elucidate the molecular mechanisms involving HACE1 and YAP1 in TC.
- To identify potential therapeutic targets for thyroid cancer intervention.
Main Methods:
- Bioinformatics analysis to identify potential miRNA-target interactions.
- Dual-luciferase reporter assays to validate miR-603 targeting of HACE1.
- In vitro cellular assays (proliferation, migration, invasion) and in vivo xenograft models.
Main Results:
- miR-603 was significantly overexpressed in thyroid cancer tissues and cells.
- miR-603 directly targets the 3'UTR of HACE1, suppressing its expression.
- HACE1 suppression by miR-603 leads to YAP1 protein stabilization, promoting TC cell proliferation, migration, and invasion.
Conclusions:
- A novel regulatory pathway involving miR-603, HACE1, and YAP1 in thyroid cancer pathogenesis was identified.
- miR-603 promotes tumor growth by stabilizing YAP1 via HACE1 targeting.
- This pathway represents a potential therapeutic target for thyroid cancer treatment.
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