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Updated: Mar 16, 2026

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
miR-497-5p inhibits cell proliferation and invasion by targeting KCa3.1 in angiosarcoma
Yaobing Chen1, Dong Kuang1, Xia Zhao1,2
1Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Abstract:
Angiosarcoma is a rare malignant mesenchymal tumor with poor prognosis. We aimed to identify malignancy-associated miRNAs and their target genes, and explore biological functions of miRNA and its target in angiosarcoma. By miRNA microarrays and reverse transcription polymerase chain reaction, we identified 1 up-regulated miRNA (miR-222-3p) and 3 down-regulated miRNAs (miR-497-5p, miR-378-3p and miR-483-5p) in human angiosarcomas compared with human capillary hemangiomas. The intermediate-conductance calcium activated potassium channel KCa3.1 was one of the putative target genes of miR-497-5p, and marked up-regulation of KCa3.1 was detected in angiosarcoma biopsy specimens by immunohistochemistry. The inverse correlation of miR-497-5p and KCa3.1 also was observed in the ISO-HAS angiosarcoma cell line at the mRNA and protein levels. The direct targeting of KCa3.1 by miR-497-5p was evidenced by reduced luciferase activity due to complementary binding of miR-497-5p to KCa3.1 mRNA 3' untranslated region. For the functional role of miR-497-5p/KCa3.1 pair, we showed that application of TRAM-34, a specific KCa3.1 channel blocker, or transfection of ISO-HAS cells with KCa3.1 siRNA or miR-497-5p mimics inhibited cell proliferation, cell cycle progression, and invasion by down-regulating cell-cycle related proteins including cyclin D1, surviving and P53 and down-regulating matrix metallopeptidase 9. In an in vivo angiosarcoma xenograft model, TRAM-34 or miR-497-5p mimics both inhibited tumor growth. In conclusion, the tumor suppressor miR-497-5p down-regulates KCa3.1 expression and contributes to the inhibition of angiosarcoma malignancy development. The miR-497-5p or KCa3.1 might be potential new targets for angiosarcoma treatment.
Insights
This study identifies miR-497-5p as a tumor suppressor in angiosarcoma by down-regulating KCa3.1. Inhibiting KCa3.1 or increasing miR-497-5p shows potential for angiosarcoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Angiosarcoma is a rare cancer with a poor prognosis.
- Identifying key molecular players in angiosarcoma development is crucial for targeted therapies.
Purpose of the Study:
- To identify microRNAs (miRNAs) and their target genes associated with angiosarcoma malignancy.
- To investigate the functional role of the miR-497-5p/KCa3.1 axis in angiosarcoma progression.
Main Methods:
- miRNA microarrays and RT-PCR to identify differentially expressed miRNAs.
- Immunohistochemistry and Western blotting to assess KCa3.1 expression.
- Luciferase assays to confirm direct targeting.
- Cell proliferation, cell cycle, and invasion assays.
- In vivo angiosarcoma xenograft models.
Main Results:
- miR-497-5p was down-regulated, while its target KCa3.1 was up-regulated in angiosarcoma.
- miR-497-5p directly targets KCa3.1 mRNA.
- Inhibition of KCa3.1 or restoration of miR-497-5p suppressed angiosarcoma cell proliferation, cell cycle progression, and invasion.
- Both KCa3.1 inhibition and miR-497-5p mimicry reduced tumor growth in vivo.
Conclusions:
- The tumor suppressor miR-497-5p inhibits angiosarcoma malignancy by down-regulating KCa3.1.
- The miR-497-5p/KCa3.1 pathway represents a potential therapeutic target for angiosarcoma.
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