This study assessed miR-675-3p-related regulatory mechanisms in
melanoma and the clinical relevance of such regulatory activities. We downloaded
miRNA mature strand expression
RNA-Seq, phenotypic, and DNA methylation data pertaining to the TCGA
Melanoma cohort. Differentially expressed
miRNAs (DEMs) between metastatic and primary
melanoma patient tissues were then identified, and miR-675-3p expression in
melanoma patient peripheral blood was confirmed using the GSE20994 GEO dataset, while its expression in
melanoma cell lines was evaluated via qRT-RCR. The clinical and prognostic implications of miR-675-3p in
melanoma were assessed, and miR-675-3p target genes were identified using bioinformatics tools. Functional roles of this
miRNA were explored via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. We identified 3 and 22
miRNAs that were up- and downregulated, respectively, in metastatic
melanoma samples relative to primary
melanoma samples. Upregulation of miR-675-3p was associated with poorer overall patient survival,
tumor histologic grade, and Clark's level. Consistently, miR-675-3p was also overexpressed in the peripheral blood of
melanoma patients relative to healthy controls, and in
melanoma cell lines relative to control cells. Gene regulatory networks indicated that 32
transcription factors control miR-675-3p expression, and that it, in turn, regulates 10 target genes. KEGG analyses indicated that these genes were associated with cell cycle, transcriptional misregulation in
cancer,
TGF-beta signaling, and HIF-1 signaling pathways. Gain-of-function assays revealed that miR-675-3p could promote cell proliferation via accelerating cell cycle progression. Western blotting results indicated that miR-675-3p could active
TGF-beta and HIF-1 signaling. Through upstream and downstream analyses of miR-675-3p-related regulatory activity, we confirmed that this
miRNA participates in key
melanoma-related processes and offers value as a prognostic
biomarker in
melanoma patients.