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Published on: January 31, 2025
Hsa_circ_0005085 may suppress cutaneous squamous cell carcinoma growth and metastasis through targeting the
Lipeng Wang1, Yuxin Liu1, Qiong Gao1
1Department of Dermatology, General Hospital of Ningxia Medical University, Yinchuan City, China.
Background:
Cutaneous squamous cell carcinoma (CSCC) is a severe malignancy derived from the skin. Mounting evidence suggests that circular RNAs (circRNAs) participate in diverse biological functions in human cancers, containing CSCC. However, the biological functions and underlying mechanism of hsa_circ_0005085 in CSCC have not been clearly studied.
Methods:
Expression levels of hsa_circ_0005085, microRNA-186-5p (miR-186-5p), and Laminin subunit gamma 1 (LAMC1) were detected by reverse transcription-quantitative polymerase chain reaction. Cell counting kit-8 assay, colony formation assay, and 5-Ethynyl-2'-deoxyuridine assay were used to assess cell proliferation. Transwell assay was conducted to detect cell migration and invasion. Cell apoptosis was analyzed by flow cytometry. Protein expression of LAMC1, E-cadherin, Snail, and slug were assessed using western blot assay. Using bioinformatics software, the binding between miR-186-5p and hsa_circ_0005085 or LAMC1 was predicted, followed by verification using a dual-luciferase reporter and RNA-Immunoprecipitation. The mouse xenograft model was established to investigate the role of hsa_circ_0005085 in vivo.
Results:
Hsa_circ_0005085 level was downregulated in CSCC tissues and cells. Overexpression of hsa_circ_0005085 inhibited cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and promoted cell apoptosis in CSCC. MiR-186-5p could restore the effect of hsa_circ_0005085 overexpression on CSCC cells, and the knockdown of LAMC1 reversed the regulation of the miR-186-5p inhibitor. In mechanism, hsa_circ_0005085 served as a sponge for miR-186-5p to regulate LAMC1 expression. Overexpression of hsa_circ_0005085 reduced growth of tumor via miR-186-5p/LAMC1 axis in vivo.
Conclusion:
In our study, hsa_circ_0005085 might inhibit CSCC development by targeting the miR-186-5p/LAMC1 axis, which might provide a promising therapeutic target for CSCC.
Insights
Circular RNAs (circRNAs) like hsa_circ_0005085 may inhibit cutaneous squamous cell carcinoma (CSCC) progression. This study reveals hsa_circ_0005085 targets the microRNA-186-5p/Laminin subunit gamma 1 axis, offering a potential therapeutic strategy for CSCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cutaneous squamous cell carcinoma (CSCC) is a significant skin malignancy.
- Circular RNAs (circRNAs) are implicated in various human cancers, including CSCC.
- The specific role and mechanism of hsa_circ_0005085 in CSCC remain underexplored.
Purpose of the Study:
- To investigate the biological functions of hsa_circ_0005085 in CSCC.
- To elucidate the underlying molecular mechanism of hsa_circ_0005085 in CSCC.
- To assess the therapeutic potential of hsa_circ_0005085 in CSCC.
Main Methods:
- Quantification of hsa_circ_0005085, microRNA-186-5p (miR-186-5p), and Laminin subunit gamma 1 (LAMC1) expression via RT-qPCR.
- Assessment of cell proliferation, migration, invasion, and apoptosis using cell counting kit-8, colony formation, EdU, Transwell, and flow cytometry assays.
- Validation of interactions using bioinformatics, dual-luciferase reporter, and RNA-Immunoprecipitation assays, alongside in vivo mouse xenograft models.
Main Results:
- Hsa_circ_0005085 was found to be downregulated in CSCC tissues and cells.
- Overexpression of hsa_circ_0005085 suppressed CSCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while promoting apoptosis.
- Hsa_circ_0005085 acts as a molecular sponge for miR-186-5p, regulating LAMC1 expression and inhibiting tumor growth in vivo via the miR-186-5p/LAMC1 axis.
Conclusions:
- Hsa_circ_0005085 exhibits tumor-suppressive functions in CSCC.
- The hsa_circ_0005085/miR-186-5p/LAMC1 axis plays a crucial role in CSCC development.
- Hsa_circ_0005085 represents a potential therapeutic target for CSCC treatment.
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