Analysis of microRNA‐203 function in CREB/MITF/RAB27a pathway: comparison between canine and human melanoma cells

Abstract

MicroRNA (miR)-203 is downregulated and acts as an anti-oncomir in melanoma cells. Here, using human and canine melanoma cells, we elucidated the effects of miR-203 on cyclic adenosine monophosphate response element binding protein (CREB)/microphthalmia-associated transcription factor (MITF)/RAB27a pathway, which is known to be important for the development and progression of human melanoma. In this study, we showed that miR-203 directly targeted CREB1 and regulated its downstream targets, MITF and RAB27a. miR-203 significantly suppressed the growth of human and canine melanoma cells and inhibited melanosome transport through the suppression of the signalling pathway. In conclusion, miR-203 was shown to be a common tumour-suppressive miRNA in human and canine melanoma and thus to play a crucial role in the biological mechanisms of melanoma development.

Control of CREB expression in tumors: from molecular mechanisms and signal transduction pathways to therapeutic target

“…During the last years miRs have been identified, which are deregulated by CREB or have CREB as direct target due to binding to its regulatory sequences at the 3′-UTR (Table 1). Using in silico prediction by different algorithms CREB expression could be regulated by different miRs known to be frequently downregulated in tumors, such as miR-181b, miR-128, miR-124, miR-34b, miR-23a, miR-200b, miR-203 and miR-301 [21, 46–49]. In some studies luciferase reporter assays confirmed the interaction of these miRs with the 3′-UTR of CREB.…”

Implication of the p53-Related miR-34c, -125b, and -203 in the Osteoblastic Differentiation and the Malignant Transformation of Bone Sarcomas

“…Interestingly, as assessed by RT-qPCR, Western blotting, and luciferase reporter assay, CREB1 was identified as a direct target of miR-203 in a multiple myeloma model ( Figure 5) [55]. Of note, this specific targeting was further confirmed by Noguchi et al in canine and human melanoma cells [159]. BMP-2 and TGF-β are able to modulate the expression of the secreted protein acidic and rich in cysteine matrix-associated protein (SPARC/osteonectin).…”

Bosutinib, an SRC inhibitor, induces caspase‐independent cell death associated with permeabilization of lysosomal membranes in melanoma cells

“…In addition, we confirmed that miR‐203 directly targeted SRC (Figure S1A‐C, Supporting Information). Earlier, we have reported that miR‐203 is downregulated and acts as an anti‐oncogene in melanoma cells . Therefore, SRC is considered to be not only activated but also possibly be overexpressed in canine and human melanoma cells.…”

“…On the other hand, SRC is known to be a target gene of anti‐oncogenic microRNA (miR)‐203 in several kinds of human cancers . Recently, we reported that miR‐203 is downregulated by DNA methylation and exhibits anti‐oncogenic functions in melanoma cells . Based on these findings, we hypothesized that SRC is overexpressed and a promising therapeutic target in melanoma.…”