MicroRNA-451a acts as tumor suppressor in cutaneous basal cell carcinoma.

Hui Sun,Pingdong Jiang

doi:10.1002/mgg3.473

Hui Sun, Pingdong Jiang

Open Access

https://doi.org/10.1002/mgg3.473

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Abstract

BackgroundBasal cell carcinoma (BCC) is the most common type of skin cancer. The underlying mechanism leading to BCC formation is not fully uncovered. The aim of this study was to characterize miRNA‐451a as a novel tumor suppressor in cutaneous BCC.MethodsWe first evaluated miRNA‐451a level in human BCC clinical tissues and inducible BCC mouse model. Then we studied the impact of overexpressing or inhibiting miR‐451a in cell proliferation, colony formation potential, and cell cycle pattern. Next, we employed luciferase reporter assay and western blotting to evaluate TBX1 as a downstream target of miRNA‐451a. Lastly, we confirmed TBX1 expressional change in BCC tissues by qPCR.ResultsmiRNA‐451a was significantly reduced in human BCC tissues. The downregulation of miRNA‐451a was also confirmed in BCC mouse model. Overexpressing miRNA‐451a in tumor cells markedly suppressed cell growth through G1 cell cycle arrest. However, inhibiting miRNA‐451a in primary cells promoted cell growth and colony formation capacity. TBX1 (602054) was predicted as a downstream target of miRNA‐451a and this was confirmed by luciferase assay and protein expression. Finally, TBX1 level was shown upregulated in BCC tissues as inversely to miR451a.ConclusionOur studies revealed that miRNA‐451a/TBX1 axis played a pivotal role in BCC tumorigenesis.

Highlights

Basal cell carcinoma (BCC) is the most common type of skin cancer
This is evidenced by the reduction of miRNA‐ 451a in BCC mouse model
Restoring miRNA‐451a expression in BCC cell line slows down cell proliferation through inducing cell cycle arrest

Summary

| INTRODUCTION

Basal cell carcinoma (BCC) is the most common type of skin cancer. It makes up about 75%–80% of non‐melanoma skin cancer. MicroRNAs (miRNA) are small single stranded noncoding RNAs of usually 22 nucleotides that play a role in regulating gene expression. MiRNA have been found to be involved in a wide array of biological processes including cell proliferation, differentiation, migration, and apoptosis They have been reported to play essential roles in many physiological or pathological processes including immune response, neurogenesis, muscle development, and cancers. MiRNA‐ 203 has been characterized as a novel tumor suppressor in BCC model It is downregulated in BCC and its downregulation leads to the activation of HH pathway that eventually contributes to BCC formation (Sonkoly et al, 2012). MiR‐451a has been reported as tumor suppressor in human glioma It impacts glioblastoma cell apoptosis, proliferation, and invasion through targeting PI3K/AKT signaling pathway (Du et al, 2015). We identified and characterized one potential downstream target of miR‐451a in BCC model and revealed the regulatory mechanism of miR‐451a in BCC pathogenesis

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Findings

| DISCUSSION