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Updated: Feb 15, 2026

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
A-to-I miR-378a-3p editing can prevent melanoma progression via regulation of PARVA expression
Guermarie Velazquez-Torres1, Einav Shoshan1, Cristina Ivan2
1Department of Cancer Biology, Unit 1906, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
Abstract:
Previously we have reported that metastatic melanoma cell lines and tumor specimens have reduced expression of ADAR1 and consequently are impaired in their ability to perform A-to-I microRNA (miRNA) editing. The effects of A-to-I miRNAs editing on melanoma growth and metastasis are yet to be determined. Here we report that miR-378a-3p is undergoing A-to-I editing only in the non-metastatic but not in metastatic melanoma cells. The function of the edited form is different from its wild-type counterpart. The edited form of miR-378a-3p preferentially binds to the 3'-UTR of the PARVA oncogene and inhibits its expression, thus preventing the progression of melanoma towards the malignant phenotype. Indeed, edited miR-378a-3p but not its WT form inhibits melanoma metastasis in vivo. These results further emphasize the role of RNA editing in melanoma progression.
Insights
RNA editing, specifically A-to-I editing of microRNA (miRNA) miR-378a-3p, is crucial for preventing melanoma metastasis. Edited miR-378a-3p inhibits the PARVA oncogene, halting cancer progression.
Area of Science:
- Molecular Biology
- Oncology
- RNA Biology
Background:
- Metastatic melanoma exhibits reduced ADAR1 expression, impairing microRNA (miRNA) A-to-I editing.
- The specific impact of miRNA editing on melanoma progression and metastasis remains largely unknown.
Purpose of the Study:
- To investigate the role and mechanism of microRNA editing in melanoma metastasis.
- To determine the function of edited miR-378a-3p in melanoma progression.
Main Methods:
- Analysis of A-to-I editing status of miR-378a-3p in metastatic and non-metastatic melanoma cells.
- In vivo metastasis assays using edited and wild-type miR-378a-3p.
- Assessment of PARVA oncogene expression following miR-378a-3p editing.
Main Results:
- miR-378a-3p undergoes A-to-I editing exclusively in non-metastatic melanoma cells.
- Edited miR-378a-3p targets the 3'-UTR of the PARVA oncogene, suppressing its expression.
- Edited miR-378a-3p effectively inhibits melanoma metastasis in vivo, unlike its wild-type form.
Conclusions:
- RNA editing of miR-378a-3p plays a critical role in suppressing melanoma metastasis.
- The edited form of miR-378a-3p acts as a tumor suppressor by inhibiting the PARVA oncogene.
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