Abstract
In this short report, we pinpoint some technical and conceptual flaws that we found in the article entitled “miR-204-5p and miR-211-5p contribute to BRAF inhibitor resistance in melanoma” (Díaz-Martínez et al., Cancer Research 2018). We also discuss how, in our opinion, these flaws led Díaz-Martínez and colleagues to incorrect conclusions about the biological role that miR-204 and miR-211 play in melanoma and about the terms of their involvement in the phenomenon of resistance to BRAF inhibitors.
Highlights
It is unclear why the authors discarded miR504 due to its low expression levels and yet they went after miR-211 that is expressed even less (Figure 1)
We and others have extensively demonstrated both in vitro and using patient data that miR-204 rather exerts its activity in sensitive cells, where its induction upon vemurafenib treatment is very robust, it targets AP1S2 and it potentiates the anti-motility effects of the drug, in turn behaving as an oncosuppressor [2, 5]
The location of the primers used for the qRT-PCR detection of TRPM1 host gene is suboptimal (Figure 2). miR-204 is likely detected instead of or together with miR-211 and this is why they both show a ~2-fold increase in expression according to qRT-PCR
Summary
It is unclear why the authors discarded miR504 due to its low expression levels and yet they went after miR-211 that is expressed even less (Figure 1). MiR-204 was chosen because its levels are ~2fold higher in A375-VR vs A375, as detected by small RNA-seq and confirmed by qRT-PCR. This claim is formally supported only by the mild decrease in proliferation that A375-VR show when transfected with a miR-204 inhibitor and exposed to vemurafenib (Figure 5E in reference 1) [3,4].
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