MicroRNA-300: A Transcellular Mediator in Exosome Regulates Melanoma Progression.

Huawen Liu,Vega Windy Karisma,Long Chen,Li Zhong

doi:10.3389/fonc.2019.01005

Huawen Liu, Vega Windy Karisma + Show 2 more

Open Access

https://doi.org/10.3389/fonc.2019.01005

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Abstract

Melanoma is a common and high-mortality skin cancer. Oxidative stress and DNA damage caused by ultraviolet light (UV) are major causative factors of melanoma formation. However, the specific molecular mechanism is still unclear. In this study, 218 dysregulated genes and 104 dysregulated miRNAs in response to UV were screened by analyzing sequencing datasets. Among them, 29 up-regulated miRNAs and 28 down-regulated miRNAs were involved in the melanoma pathway. As the only differential gene in the melanoma pathway, GADD45B severely affects the prognosis of melanoma patients. MiR-300 is the only differentially expressed miRNA that regulates GADD45B. In addition, compared to normal melanocytes, miR-300 was significantly down-regulated in melanoma cells (log FC = −1.63) and exosomes (log FC = −1.34). Among the transcription factors predicted to regulate miR-300, MYC, PPARG, and ZIC2 were significantly up-regulated in melanoma cells, and TP53, JUN, JUNB, FOS, and FOSB interacted with GADD45B. We attempted to reveal the pathogenesis of melanoma and screen new biomarkers by constructing a TF-mRNA-miRNA axis in turn to provide a view for further research.

Highlights

Melanoma is one type of skin cancer with high incidence, poor prognosis, and a complicated mechanism
UVR damage in skin is mainly divided into two types, acute injury caused by high-dose UVR in a short time and chronic damage caused by perennial small-dose UVR
There were 97 biological process (BP) terms, 25 cellular component (CC) terms, 32 molecular function (MF) terms, and 20 pathways associated with Differentially expressed genes (DEGs) (Figure S2)

Summary

Introduction

Melanoma is one type of skin cancer with high incidence, poor prognosis, and a complicated mechanism. The greatest source of UVR reaching the earth is sunlight, composed of 95% UVA (320–340 nm) and 5% UVB (290–320 nm), while UVC is blocked by the aerosphere [1, 2]. Both UVA and UVB could cause DNA damage and alter the skin microenvironment [3,4,5]. Epidemiological studies suggest potential roles of UVA and UVB in melanoma formation, but the comparative importance of these studies remains controversial. In the epidermal layer of the skin, melanocytes and surrounding keratinocytes form the melanin units [6]. UVR activates signaling cascade that could induce melanin synthesis in melanocytes [7,8,9,10]

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