Related Experiment Video
Updated: Dec 9, 2025

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
ADAR1 regulates melanoma cell invasiveness by controlling beta3-integrin via microRNA-30 family members
Yael Nemlich1, Michal J Besser1,2, Jacob Schachter1,3
1Ella Lemelbaum Institute for Immuno-Oncology Israel.
Abstract:
Melanoma cells utilize multiple mechanisms to exit the primary tumor mass, invade the surroundings and subsequently distant tissues. We have previously reported that the expression of the RNA editing enzyme ADAR1 (adenosine deaminase acting on RNA) is downregulated in metastatic melanoma, which facilitates proliferation and invasion. Here we show that ADAR1 controls melanoma invasiveness by regulating ITGB3 expression via miR-30a and miR-30d. ADAR1 overexpression or knockdown leads to an increase or decrease, respectively, in the expression of both microRNAs. The effect is independent of RNA-editing. Dual luciferase assays show that both microRNAs directly regulate the expression of the ITGB3 integrin. Overexpression of the miR-30a or miR-30d lead to a decrease in ITGB3 and a resultant decreased invasive and metastatic capacities. Neutralization of the endogenous miR-30a or miR-30d leads to the opposite effect. The microRNAs regulate ITGB3 levels probably through a post-transcriptional effect, as both mRNA and protein levels of ITGB3 are affected. These results further expand our knowledge on the ADAR1-ITGB3 network and its central role in acquisition of the invasive phenotype of metastatic melanoma.
Insights
The RNA editing enzyme ADAR1 (adenosine deaminase acting on RNA) regulates melanoma cell invasion by controlling ITGB3 expression through miR-30a and miR-30d. This discovery offers new insights into melanoma metastasis.
Area of Science:
- Oncology
- Molecular Biology
- RNA Biology
Background:
- Metastatic melanoma cells exhibit complex invasion mechanisms.
- Adenosine deaminase acting on RNA (ADAR1) expression is reduced in metastatic melanoma, correlating with increased proliferation and invasion.
Purpose of the Study:
- To elucidate the role of ADAR1 in controlling melanoma cell invasiveness.
- To investigate the regulatory pathway involving ADAR1, microRNAs, and ITGB3 in melanoma metastasis.
Main Methods:
- Investigated the effect of ADAR1 overexpression and knockdown on microRNA expression.
- Utilized dual luciferase assays to confirm direct interaction between microRNAs and ITGB3.
- Assessed the impact of microRNA modulation on ITGB3 levels and melanoma cell invasiveness.
Main Results:
- ADAR1 influences the expression of miR-30a and miR-30d, independent of its RNA-editing activity.
- Both miR-30a and miR-30d directly target and downregulate ITGB3 (integrin beta 3) expression.
- Modulating miR-30a/30d levels altered ITGB3 expression and consequently affected melanoma cell invasion and metastasis.
Conclusions:
- ADAR1 plays a critical role in regulating melanoma invasiveness by modulating the miR-30a/miR-30d-ITGB3 axis.
- This pathway represents a significant mechanism in the acquisition of the invasive phenotype in metastatic melanoma.
- Findings expand understanding of the ADAR1-ITGB3 network in melanoma progression.
Related Concept Videos
Cancer Cell Migration through Invadopodia
MicroRNAs
MicroRNAs
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Intracellular Signaling Affects Focal Adhesions
Some...
Regulation of Angiogenesis and Blood Supply

