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Updated: Nov 8, 2025
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Identification of Metastasis-Associated MicroRNAs in Metastatic Melanoma by miRNA Expression Profile and Experimental
Yunshu Gao1, Jiahua Xu2, Hongwei Li2
1Department of Oncology, People's Liberation Army (PLA) General Hospital, Beijing, China.
Abstract:
It is reported that microRNAs (miRNA) have paramount functions in many cellular biological processes, development, metabolism, differentiation, survival, proliferation, and apoptosis included, some of which are involved in metastasis of tumors, such as melanoma. Here, three metastasis-associated miRNAs, miR-18a-5p (upregulated), miR-155-5p (downregulated), and miR-93-5p (upregulated), were identified from a total of 63 different expression miRNAs (DEMs) in metastatic melanoma compared with primary melanoma. We predicted 262 target genes of miR-18a-5p, 904 miR-155-5p target genes, and 1220 miR-93-5p target genes. They participated in pathways concerning melanoma, such as TNF signaling pathway, pathways in cancer, FoxO signaling pathway, cell cycle, Hippo signaling pathway, and TGF-beta signaling pathway. We identified the top 10 hub nodes whose degrees were higher for each survival-associated miRNA as hub genes through constructing the PPI network. Using the selected miRNA and the hub genes, we constructed the miRNA-hub gene network, and PTEN and CCND1 were found to be regulated by all three miRNAs. Of note, miR-155-5p was obviously downregulated in metastatic melanoma tissues, and miR-18a-5p and miR-93-5p were obviously regulated positively in metastatic melanoma tissues. In validating experiments, miR-155-5p's overexpression inhibited miR-18a-5p's and miR-93-5p's expression, which could all significantly reduce SK-MEL-28 cells' invasive ability. Finally, miR-93-5p and its potential target gene UBC were selected for further validation. We found that miR-93-5p's inhibition could reduce SK-MEL-28 cell's invasive ability through upregulated the expression of UBC, and the anti-invasive effect was reserved by downregulation of UBC. The results show that the selected three metastasis-associated miRNAs participate in the process of melanoma metastasis via regulating their target genes, providing a potential molecular mechanism for this disease.
Insights
Three microRNAs (miRNAs) are linked to melanoma metastasis. Upregulated miR-18a-5p and miR-93-5p, and downregulated miR-155-5p, impact cancer cell invasion by regulating target genes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) play crucial roles in cellular processes, including tumor metastasis.
- Melanoma metastasis involves complex molecular mechanisms, with miRNAs implicated in its progression.
Purpose of the Study:
- To identify and characterize metastasis-associated microRNAs (miRNAs) in melanoma.
- To elucidate the molecular mechanisms by which these miRNAs regulate melanoma metastasis.
Main Methods:
- Differential expression analysis of miRNAs in metastatic versus primary melanoma.
- Bioinformatic prediction of miRNA target genes and pathway analysis.
- Construction of protein-protein interaction (PPI) and miRNA-hub gene networks.
- In vitro validation of miRNA functions and target gene interactions in melanoma cells.
Main Results:
- Identified three differentially expressed miRNAs: miR-18a-5p (upregulated), miR-155-5p (downregulated), and miR-93-5p (upregulated) in metastatic melanoma.
- Predicted numerous target genes involved in key melanoma-related pathways (e.g., TNF signaling, cell cycle).
- Demonstrated that overexpression of miR-155-5p inhibited miR-18a-5p and miR-93-5p, reducing melanoma cell invasion.
- Showed that miR-93-5p inhibition reduced cell invasion by upregulating UBC expression.
Conclusions:
- The identified miRNAs (miR-18a-5p, miR-155-5p, miR-93-5p) are significantly associated with melanoma metastasis.
- These miRNAs regulate melanoma cell invasion through their target genes, offering potential therapeutic targets.
- The study provides insights into the molecular mechanisms underlying melanoma metastasis involving specific miRNA-gene interactions.
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