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Published on: August 18, 2023
miR-590-5p suppresses hepatocellular carcinoma chemoresistance by targeting YAP1 expression
Minjiang Chen1, Liming Wu2, Jianfei Tu1
1Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, The Central Hospital of Zhejiang Lishui, 323000 Lishui, Zhejiang, PR China; Department of Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, The Central Hospital of Zhejiang Lishui, 323000 Lishui, Zhejiang, PR China.
Background:
Resistance to chemotherapeutic treatment is a common phenomenon in cancers, especially in hepatocellular carcinoma (HCC). The Hippo signaling pathway has been demonstrated to play a role in tumor initiation, development, and progression. However, little is known about its roles in the HCC chemoresistance.
Methods:
In this study, real-time PCR and western blotting were used to identify the expression profile of key components of Hippo signaling pathway between chemoresistant and chemosensitive HCC cell lines. In vitro and in vivo loss- and gain-of-function studies were performed to reveal the effects and related mechanism of microRNA-590-5p/YAP1 axis in the chemoresistant phenotype of HCC cells.
Findings:
We identified yes-associated protein 1 (YAP1) as the major dysregulated molecules in adriamycin (ADR)-resistant HCC cells. YAP1 was profoundly implicated in the chemoresistant phenotype of HCC cells. Furthermore, microRNA-590-5p was revealed as a functional modulator of YAP1. Importantly, YAP1-mediated chemoresistant phenotype was closely related to increased expression of stemness markers and ATP-binding cassette transporters. HCC patients with poor response to transarterial chemoembolization (TACE) treatment had higher protein level of YAP1 than that in the responsive patients.
Interpretation:
The microRNA-590-5p/YAP axis plays an important role in the chemotherapeutic resistance of HCC cells, suggesting new adjuvant chemotherapeutic directions in HCC. FUND: National Natural Science Foundation of China, Zhejiang Province Medical and Health Care Key Project, Experimental Animal Science and Technology Projects of Zhejiang Province, Public Welfare Technology Application Research Project of Lishui, Chinese Medicine Science and Technology Projects of Zhejiang Province.
Insights
This study reveals that the microRNA-590-5p/YAP1 axis drives hepatocellular carcinoma (HCC) chemoresistance by regulating stemness markers and transporters. Targeting this axis may offer new strategies for treating resistant HCC.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Hepatocellular carcinoma (HCC) frequently exhibits resistance to chemotherapy.
- The Hippo signaling pathway is implicated in cancer development but its role in HCC chemoresistance is unclear.
Purpose of the Study:
- To investigate the role of the Hippo signaling pathway in hepatocellular carcinoma (HCC) chemoresistance.
- To elucidate the mechanism of microRNA-590-5p and YAP1 in HCC chemoresistance.
Main Methods:
- Real-time PCR and western blotting to analyze Hippo pathway components in chemoresistant vs. chemosensitive HCC cells.
- In vitro and in vivo loss- and gain-of-function studies to assess the microRNA-590-5p/YAP1 axis.
- Correlation analysis between YAP1 protein levels and patient response to transarterial chemoembolization (TACE).
Main Results:
- Yes-associated protein 1 (YAP1) was identified as a key dysregulated molecule in adriamycin (ADR)-resistant HCC cells.
- MicroRNA-590-5p was found to functionally modulate YAP1.
- YAP1-mediated chemoresistance was linked to increased stemness markers and ATP-binding cassette transporters.
- Higher YAP1 protein levels were observed in HCC patients with poor response to TACE.
Conclusions:
- The microRNA-590-5p/YAP1 axis is crucial for chemotherapeutic resistance in HCC.
- This axis represents a potential therapeutic target for overcoming chemoresistance in HCC.
- Findings suggest novel adjuvant chemotherapeutic strategies for HCC treatment.
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