miR-145-5p regulates hepatocellular carcinoma malignant advancement and immune escape via down-regulation of AcylCoA synthase ACSL4
Hepatocellular carcinoma (HCC) exhibits a subtle onset, high incidence rates, and low survival rates, becoming a substantial threat to human health. Hence, it is crucial to discover fresh biomarkers and treatment targets for the early detection and management of HCC. CCK-8, scratch-wound, and transw...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2024-12-01
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| Series: | Biomolecules & Biomedicine |
| Subjects: | |
| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/11209 |
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| Summary: | Hepatocellular carcinoma (HCC) exhibits a subtle onset, high incidence rates, and low survival rates, becoming a substantial threat to human health. Hence, it is crucial to discover fresh biomarkers and treatment targets for the early detection and management of HCC. CCK-8, scratch-wound, and transwell assays were used to evaluate the biological properties of HCC cell lines (Huh-7 and Hep3B). Bioinformatics analysis identified the downstream target mRNA of miR-145-5p as acyl-CoA synthetase long-chain family member 4 (ACSL4). RT-qPCR was used to test miR-145-5p and ACSL4 levels. Transwell chambers were used to co-incubate purified CD8+ T cells and HCC cells for 48 h, and the effect of CD8+ T cells on apoptosis in HCC cells was detected by flow cytometry. A subcutaneous graft tumor model was constructed, and ELISA kits were used to assess cytokine levels and CD8+ T cell activation markers. HCC cells showed a decline in miR-145-5p levels and a rise in ACSL4 levels. Overexpression of miR-145-5p hindered HCC cell proliferation, migration, and invasion, while stimulating CD8+ T cell activation. Conversely, overexpression of ACSL4 enhanced the malignant biological properties of HCC cells and reduced the effect of CD8+ T cells, while silencing ACSL4 had the opposite effect. miR-145-5p targeted and downregulated ACSL4, while overexpression of miR-145-5p weakened the promotion of HCC malignant progression caused by ACSL4 overexpression. Additionally, overexpression of miR-145-5p and silencing ACSL4 were effective in inhibiting tumor growth in vivo. In conclusion, miR-145-5p targets and downregulates ACSL4, leading to the inhibition of HCC malignant progression and preventing immune escape in HCC cells.
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| ISSN: | 2831-0896 2831-090X |