<p>MicroRNA-3662 targets ZEB1 and attenuates the invasion of the highly aggressive melanoma cell line A375</p>

Abstract

Background Cutaneous melanoma is the most aggressive form of skin cancer. It accounts for approximately 5% of all cutaneous malignancies and is currently responsible for the majority of skin cancer-related deaths. However, the exact mechanisms responsible for the occurrence of melanoma, in particular the invasive growth in normal skin or muscle tissue, remain unknown. Materials and methods miR-3662, a microRNA is a potential tumor suppressor targeting zinc finger E-box binding homeobox 1 (ZEB1), which functions as a key regulator of the epithelial-mesenchymal transition (EMT) process. This microRNA was identified using an online database (miRDB) and expression was confirmed by Western blot analysis. Quantitative polymerase chain reaction (qPCR) was used to examine whether miR-3662 inhibits the EMT process in the aggressive melanoma cell line, A375, through the modification of the expression of invasion-related genes in A375 cells. The effects of miR-3662 on the in vivo growth of A375 cells were examined in a nude mouse model. Results Using virtual screening of the miRDB database, miR-3662 was shown to target the 3ʹ untranslated region (UTR) of the ZEB1 gene. Expression of miR-3662 via a lentivirus vector significantly decreased protein levels of ZEB1 and inhibited the growth of A375 cells in vitro and in vivo. The reduction in ZEB1 expression induced by miR-3662 resulted in EMT inhibition in A375 cells and decreased the relative expression of metastasis genes. Conclusion Down-regulation of ZEB1’s expression via miR-3662 lentivirus vectors significantly decreased the in vitro and in vivo growth of the highly aggressive melanoma cell line A375.

CRISPR interference and activation of the microRNA-3662-HBP1 axis control progression of triple-negative breast cancer

“…However, later studies revealed that miR-3662 inhibits hepatocellular carcinoma growth through decreasing the HIF-1α-mediated Warburg effect 15 or upregulating hexokinase 2 (HK2) 16 . Also, in aggressive melanoma cells, miR-3662 inhibits the epithelial-mesenchymal transition (EMT) through down-regulation of zinc finger E-box binding homeobox 1 (ZEB1) 17 . However, the functional role of miR-3662 in human cancers remains undefined.…”

miR-548b Suppresses Melanoma Cell Growth, Migration, and Invasion by Negatively Regulating Its Target Gene HMGB1

“…17 In the highly aggressive melanoma cell line, A375, miRNA-3662 targets zinc finger E-box binding homeobox 1 (ZEB1) and attenuates the invasion of melanoma cells in vitro. 23 Recently, miRNA-548b has been found to inhibit the aggressiveness of hepatocellular carcinoma (HCC) by regulating the high mobility group protein 1 (HMGB1). 24 In addition, miR-548b restrains the growth and aggressiveness of glioma by targeting metastasis tumor-associated protein-2 (MTAP2).…”

Innate and Adaptive Immunity Linked to Recognition of Antigens Shared by Neural Crest-Derived Tumors

“…In another work, Zhu and colleagues showed that the over-expression of miR-3662 halted the EMT program, affecting the expression of matrix metalloproteinases 3 and 9. In addition, these authors demonstrated that miR-3663 inhibited EMT process by targeting the transcription factor ZEB1 (proto-oncogene zinc finger E-box binding homeobox 1) and therefore blocking the transition of epithelial cells to a mesenchymal condition [56]. The EMT phenotype is common in cancer stem melanoma cell characterized by a positivity for CD133 and PD1 and by CSC intracellular markers comprise enzymes such as aldehyde dehydrogenases (ALDH), and transcription factors such as Sox2 and Klf4.…”