Let7i Restoration Inhibits Migration and Proliferation While Inducing Apoptosis in Melanoma Cells by Directly Targeting CXCR4 In Vitro

Background: Melanoma is a type of skin cancer that originates from the mutation of melanocytes. miRNAs are small non-coding RNA molecules that bind to their target mRNA and regulate many biological processes. Aberrant expression of microRNAs has been reported in different types of cancer. The present study aimed to determine the role of Let7i in melanoma cancer pathogenesis. Methods: In this study, we evaluated the expression level of Let-7 and its potential target genes in specimens obtained from melanoma patients. Then, we transfected the Let-7i mimic and assessed its effect on cell migration, proliferation, and apoptosis using the Scratch test, MTT assay, and Flow cytometry, respectively. Then, the impact of Let7i restoration on chemokine receptor type 4 (CXCR4) expression was assessed by real-time polymerase chain reaction (PCR) and Western blotting. A rescue experiment was performed to determine the association between Let-7 and CXCR4 in melanoma pathogenesis. Moreover, the correlation between Let-7a and CXCR4 expression and clinicopathological features of the patients was evaluated. Results: The results indicated that Let-7a was down-regulated, while CXCR4 was up-regulated in specimens derived from melanoma patients. It was also discovered that transfection of Let-7i alleviated the proliferative and metastatic capacity of SK-MEL-3 melanoma cells and led to an increased apoptosis rate in these cells. Rescue experiments demonstrated that Let-7 reduced the metastatic potential of melanoma cells by directly targeting CXCR4. Additionally, a correlation was observed between Let-7 and CXCR4 with lymph node metastasis. Conclusion: This study reveals that Let-7 serves as a potential tumor-suppressor in melanoma by directly targeting CXCR4, indicating a possible therapeutic and diagnostic candidate for patients suffering from melanoma.