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Overexpression of circ_0001445 decelerates hepatocellular carcinoma progression by regulating miR-942-5p/ALX4 axis
Qinhong Xu1, Lijing Zhou1, Ganghua Yang1
1Department of Geriatric Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, Yanta West Road, Xi'an, 710061, Shaanxi, China.
Abstract:
Circular RNAs (circRNAs) have been verified to have essential regulatory roles in diverse human cancers, including hepatocellular carcinoma (HCC). In this study, we aimed to explore the roles of circ_0001445 in HCC. Herein, circ_0001445 was decreased and miR-942-5p was increased in HCC tissues and cells. Circ_0001445 overexpression or miR-942-5p inhibition repressed cell cycle process, migration, invasion, epithelial-mesenchymal transition and glycolysis in HCC cells. Mechanistically, circ_0001445 could promote ALX4 expression through targeting miR-942-5p. Moreover, miR-942-5p overexpression reversed the inhibitory effect of circ_0001445 on HCC cell progression. The effect of miR-942-5p on HCC cell development was rescued following the elevation of ALX4. In addition, circ_0001445 overexpression restrained tumorigenesis in vivo. In conclusion, circ_0001445 played a negative role in HCC progression by modulating miR-942-5p/ALX4 axis, which might provide a novel target for HCC therapy.
Insights
Circular RNAs (circRNAs) regulate hepatocellular carcinoma (HCC). This study shows circ_0001445 inhibits HCC progression by targeting the miR-942-5p/ALX4 pathway, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are crucial in human cancer development.
- Hepatocellular carcinoma (HCC) is a significant global health concern.
- The specific role of circ_0001445 in HCC remains largely unexplored.
Purpose of the Study:
- To investigate the function and mechanism of circ_0001445 in hepatocellular carcinoma.
- To elucidate the regulatory relationship between circ_0001445, miR-942-5p, and ALX4 in HCC.
Main Methods:
- Quantitative real-time PCR to measure circRNA and miRNA expression.
- Cell-based assays to assess proliferation, migration, invasion, and epithelial-mesenchymal transition.
- In vivo tumor xenograft models to evaluate tumorigenesis.
- Bioinformatic analysis and molecular experiments to confirm targeting interactions.
Main Results:
- circ_0001445 expression was significantly downregulated in HCC tissues and cells.
- Overexpression of circ_0001445 or inhibition of miR-942-5p suppressed HCC cell proliferation, migration, invasion, EMT, and glycolysis.
- circ_0001445 acts as a sponge for miR-942-5p, thereby increasing ALX4 expression.
- miR-942-5p overexpression or ALX4 knockdown reversed the inhibitory effects of circ_0001445.
- circ_0001445 overexpression inhibited HCC tumorigenesis in vivo.
Conclusions:
- circ_0001445 functions as a tumor suppressor in HCC by regulating the miR-942-5p/ALX4 axis.
- circ_0001445 may serve as a novel diagnostic biomarker and therapeutic target for HCC.
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