Table 5.

Therapeutic interventions attenuating miR-21 expression.

Therapeutic Factors	Potential Benefits for Melanoma Prevention and Therapy	References
Anti-miR-21	Direct suppression of miR-21 signaling in melanocytes, activation of skin-resident CD8+ memory T-cells; reduction of miR-21 in tumor-associated macrophages associated with improved cytotoxic T-cell responses	[33,366,367,368,369,370,371]
BRAF inhibition	Attenuation of miR-21 expression	[336]
Sunscreen	Reduction of keratinocyte-derived exosomal miR-21	[163,164,165,166,167]
Restriction of electro-magnetic radiation	Limitation of smart phone radiation on miR-21 expression	[189,190]
Control of birth weight and body weight	Balanced expression of miR-21 during fetal and postnatal life	[203,204]
Reduction of glycemic load and fat intake	Reduction of circulating and adipocyte-derived miR-21	[60,230,231,256]
Cessation of smoking	Reduction of airway epithelial cell-derived exosomal miR-21	[287,288,289]
Restriction of alcohol intake	Reduction of miR-21 expression	[276,277]
Metformin	Reduction of STAT3 activation and miR-21 expression	[349,350,352,353]
Beta-blocker	Suppression of STAT3 activation and miR-21 expression	[364]
Curcumin	Suppression of STAT3 activation and inactivation of AP-1 resulting in reduced expression of miR-21	[380,381,382,383]
EGCG	Reduction of miR-21 expression	[397,398]
Sulforaphane	Reduction of miR-21 expression	[388,389]
Vitamin D	Reduction of miR-21 expression	[54,95,307]
Exercise	Reduction of miR-21 expression	[334,335]
HIFU	Reduction of miR-21 in metastatic melanoma tissue	[376]