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Updated: Oct 25, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Circular RNA ZNF609 drives tumor progression by regulating the miR-138-5p/SIRT7 axis in melanoma
Quan Liu1, Wei Cui1, Chao Yang2
1Department of Plastic Surgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, Sichuan, China.
Abstract:
Melanoma serves as a prevailing and lethal skin malignancy with high mortality and a growing number of patients globally. Circular RNAs (circRNAs), as a type of emerging cellular regulator, are involved in the modulation of melanoma. Nevertheless, the function of circZNF609 in melanoma development remains obscure. In this study, we were interested in the effect and the underlying mechanism of circZNF609 on DNA damage during melanoma progression. The circZNF609 depletion significantly suppressed melanoma cell invasion, migration, and proliferation, and stimulated apoptosis. Meanwhile, comet assays showed that the tail length and γH2AX levels were elevated by circZNF609 depletion. Mechanically, circZNF609 sponged miR-138-5p and miR-138-5p targeted SIRT7 in the melanoma cells. The SIRT7 overexpression and miR-138-5p inhibitor could reverse circZNF609 depletion-mediated DNA damage and malignant progression in melanoma cells. Functionally, CircZNF609 promoted cell growth of melanoma in the nude mice. Consequently, we conclude that circZNF609 suppresses DNA damage and potentially enhances melanoma progression at the experimental condition by modulating the miR-138-5p/SIRT7 axis. Our finding provides new insights into the mechanism by which circZNF609 modulates the development of melanoma. CircZNF609 and miR-138-5p may be utilized as therapeutic targets for melanoma.
Insights
Circular RNA ZNF609 (circZNF609) suppresses DNA damage and promotes melanoma progression by regulating the miR-138-5p/SIRT7 pathway. This finding offers potential therapeutic targets for melanoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Melanoma is a deadly skin cancer with increasing incidence.
- Circular RNAs (circRNAs) are emerging regulators in cancer, but circZNF609's role in melanoma is unknown.
Purpose of the Study:
- To investigate the effect of circZNF609 on DNA damage in melanoma progression.
- To elucidate the underlying molecular mechanism of circZNF609 in melanoma.
Main Methods:
- Depletion of circZNF609 in melanoma cells.
- Comet assays to assess DNA damage.
- MiRNA sponging assays and Western blotting to analyze molecular interactions.
- In vivo tumor growth assays in nude mice.
Main Results:
- circZNF609 depletion inhibited melanoma cell invasion, migration, proliferation, and induced apoptosis.
- circZNF609 depletion increased DNA damage markers (tail length, γH2AX).
- circZNF609 acts as a sponge for miR-138-5p, which targets SIRT7, and this axis mediates DNA damage and melanoma progression.
Conclusions:
- circZNF609 suppresses DNA damage and promotes melanoma progression via the miR-138-5p/SIRT7 axis.
- circZNF609 and miR-138-5p represent potential therapeutic targets for melanoma.
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