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ADAR1-mediated regulation of melanoma invasion
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Journal Article
ADAR1-mediated regulation of melanoma invasion
2018
Overview
Melanoma cells use different migratory strategies to exit the primary tumor mass and invade surrounding and subsequently distant tissues. We reported previously that ADAR1 expression is downregulated in metastatic melanoma, thereby facilitating proliferation. Here we show that ADAR1 silencing enhances melanoma cell invasiveness and ITGB3 expression. The enhanced invasion is reversed when ITGB3 is blocked with antibodies. Re-expression of wild-type or catalytically inactive ADAR1 establishes this mechanism as independent of RNA editing. We demonstrate that ADAR1 controls ITGB3 expression both at the post-transcriptional and transcriptional levels, via miR-22 and PAX6 transcription factor, respectively. These are proven here as direct regulators of ITGB3 expression. miR-22 expression is controlled by ADAR1 via FOXD1 transcription factor. Clinical relevance is demonstrated in patient-paired progression tissue microarray using immunohistochemistry. The novel ADAR1-dependent and RNA-editing-independent regulation of invasion, mediated by ITGB3, strongly points to a central involvement of ADAR1 in cancer progression and metastasis.
In metastatic melanoma, ADAR1 is downregulated, facilitating proliferation. Here, the authors show an ADAR1-dependent and RNA-editing-independent regulation of melanoma invasion mediated by ITGB3 expression, which can be reversed when ITGB3 is blocked.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 13/109
/ 13/51
/ 13/89
/ 3' Untranslated Regions - genetics
/ Adenosine Deaminase - genetics
/ Adenosine Deaminase - metabolism
/ Cancer
/ Control
/ Editing
/ Gene Expression Regulation, Neoplastic
/ Humanities and Social Sciences
/ Humans
/ Melanoma
/ RNA
/ RNA-Binding Proteins - genetics
/ RNA-Binding Proteins - metabolism
/ Science
