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Comment
. 2021 Feb;141(2):250-252.
doi: 10.1016/j.jid.2020.07.010.

The Melanocyte Lineage Factor miR-211 Promotes BRAFV600E Inhibitor Resistance

Stephen M Ostrowski  1 , David E Fisher  2
Affiliations
Comment

The Melanocyte Lineage Factor miR-211 Promotes BRAFV600E Inhibitor Resistance

Stephen M Ostrowski et al. J Invest Dermatol. 2021 Feb.

Abstract

Resistance to targeted therapy and immunotherapy remains a major obstacle in improving care for patients with advanced melanoma. MicroRNAs play important roles in regulating gene networks involved in disease progression and resistance to therapy in cancers such as melanoma. MicroRNA miR-211 contributes to melanocyte and melanoma biology and has been implicated in targeted therapy resistance. Lee et al. (2020) report a novel mechanism by which miR-211 promotes resistance to BRAFV600E inhibitor therapy via the upregulation of the extracellular signal-regulated kinase 5 signaling pathway.

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Conflict of interest statement

Conflict of Interest

Dr. Fisher has a financial interest in Soltego, Inc., a company that is developing SIK inhibitors for topical skin darkening treatments that might be used for a broad set of human applications. Dr. Fisher’s interests were reviewed and are managed by Massachusetts General Hospital and Partners Healthcare in accordance with their conflict of interest policies.

Figures

Figure 1.
Figure 1.. miR-211 drives BRAFi resistance through DUSP6/ERK5 axis.
Resistance to BRAFi inhibitor treatment in many cases is driven by upregulation of the MITF transcription factor. miR-211 is located genomically within intron 6 of the TRPM1 gene and TRPM1/miR211 are regulated transcriptionally by MITF. Lee et al. demonstrate that miR-211 targets DUSP6 to prevent its expression, leading to ERK5 activation which in turn drives proliferation and BRAFi resistance of A375 melanoma cells.
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