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Cancer cell migration and invasion depend on dynamic actin cytoskeleton remodeling and extracellular matrix (ECM) adhesion, processes amenable to simultaneous modulation by microRNAs (miRNAs). Here, we investigated the role of miR-135a-5p in regulating actin dynamics and focal adhesion organization in B16F1 melanoma cells. We show that miR-135a-5p mimic transfection reduces actin cytoskeleton dynamics, slows actin filament turnover, and increases the stable F-actin pool, demonstrated by live cell imaging and fluorescence recovery after photobleaching (FRAP). We further revealed that miR-135a-5p mimic expression reduces focal adhesion number and size selectively on laminin. We identified Growth arrest-specific 7 (Gas7), an F-BAR domain-containing regulator of actin dynamics and membrane protrusion, as a novel target of miR-135a-5p, validated by luciferase reporter assay and Western blot. Gas7 overexpression rescued miR-135a-5p mimic induced focal adhesion phenotype on laminin. Together these findings revealed that miR-135a-5p fine-tunes the actin dynamics and focal adhesion number, size and location. Focal adhesion phenotype was rescued by restoring the Gas7 expression. It is probable that changes in actin cytoskeleton and focal adhesions result in observed decrease in cell dynamics. Furthermore, measured changes provide a plausible explanation for how levels of miRNA-135a-5p regulate cancer cell migration, adhesion and ultimately metastatic dissemination.