Elsevier

Gene

Volume 637, 30 December 2017, Pages 196-202
Gene

Research paper
Epidermal long non-coding RNAs are regulated by ultraviolet irradiation

https://doi.org/10.1016/j.gene.2017.09.043Get rights and content

Highlights

  • Epidermal lncRNAs and mRNAs changed after UVB irradiation are analyzed.

  • Immune response-related genes are activated by UVB irradiation

  • lncRNAs affected by UVB irradiation and skin tumorigenesis are identified.

Abstract

Ultraviolet (UV) radiation causes the harmful effects on skin by the photochemical reaction and gene expression regulation. Recent evidences have shown that long non-coding RNAs (lncRNAs) play critical roles in a diverse range of biological functions. However, research on the effects of UV irradiation on lncRNA expression in epidermal cells is limited. The aim of this study was to identify changes in the expression profile of lncRNAs after UVB irradiation. To accomplish this, we performed a microarray analysis of both mRNA and lncRNA expression levels in irradiated skin cells. Gene ontology (GO) analysis of differentially expressed mRNAs showed that the expression of immune response- and cell membrane-related genes was up-regulated, while cell-cell adhesion-associated genes were down-regulated by UVB irradiation. Moreover, we found that lncRNAs up-regulated by UVB irradiation were associated with the regulation of gene transcription, while lncRNAs down-regulated by UVB irradiation were associated with tumorigenesis. Finally, we compiled a list of the lncRNAs that showed the strongest association with the development of non-melanoma skin cancers caused by UV exposure. These findings lay a foundation for future investigations into the expression patterns of lncRNAs with roles in the response to UV irradiation and in non-melanoma skin cancers.

Introduction

The epidermis, the outermost layer of the skin, is the primary protective barrier that shields the internal organs from physical and chemical damage. Exposure to ultraviolet (UV) radiation from sunlight is the main cause of non-melanoma skin cancer, as UV irradiation weakens the protective function of skin (Feehan and Shantz, 2016). According to wavelength, UVs are classified as UVA at 320–400 nm, UVB at 290–320 nm, and UVC at shorter ray. UV exposure damages the cell in various ways (Cornaghi et al., 2016, Zeng et al., 2016). UVB exposure especially causes the damage of epidermal layer and further leads to the development of skin cancer (Bowden, 2004). Exposure to UVB light causes the mutation of DNA by inducing the dimerization of adjacent pyrimidine residues (Ikehata and Ono, 2011). In addition, UVB irradiation alters gene expression patterns by disrupting various cell-signaling pathways (Sesto et al., 2002, El-Abaseri et al., 2006).

In recent years, a large number of non-coding RNAs (ncRNAs)—RNAs that are not translated into proteins—have been identified by transcriptional analysis. Any ncRNAs longer than 200 nucleotides are generally classified as long ncRNAs (lncRNAs), which are emerging as important regulators of several cellular processes such as development and differentiation, as well as multiple pathological processes including tumorigenesis (Fatica and Bozzoni, 2014, Adams et al., 2017).

Although many genes and signaling pathways affected by UV irradiation have been described, there are relatively few studies on the effects of UV irradiation on the expression of lncRNAs in epidermal cells. In this study, we conducted a microarray analysis to evaluate the transcriptional profile of lncRNAs after UVB irradiation in keratinocytes.

Section snippets

Cell culture

Human primary epidermal keratinocytes were obtained from Lonza (Walkersville, MD, USA) and were maintained in serum-free KGM-Gold media with Bullet-kit supplements (Lonza). For UVB irradiation, keratinocytes were grown to 70% confluences, then the culture medium was replaced with phosphate buffered saline. 30 mJ/cm2 UVB irradiation was performed using the BIO-SUN irradiation system (Vilber Lourmat, Torcy, France) with peak wavelength at 312 nm.

Microarray analysis

Total RNAs from two independent biological replicates

Analysis of differentially expressed mRNAs and lncRNAs after UVB irradiation

To investigate the changes in lncRNA expression after UVB irradiation, microarray analysis was then performed. Then, differentially expressed lncRNAs and mRNAs were analyzed after checking the quality of RNAs (Supplementary Table 1) and normalizing the band intensities (Fig. 1A). The expression of several lncRNAs and mRNAs was significantly altered, as shown in heat maps with hierarchical clustering (Fig. 1B). Top 20 mRNAs and lncRNAs changed by UVB irradiation were listed Supplementary Table 2

Discussion

UV irradiation is a major environmental carcinogen for the skin. UVB (~ 280–320 nm) radiation is absorbed by the epidermis, damaging the cells. These damaged cells have the potential to progress to a cancerous state (Ikehata and Ono, 2011). Recently, lncRNAs have gained massive attention as they play critical roles in essential biological processes and pathological conditions (Hombach and Kretz, 2013, Schmitz et al., 2016).

Previous studies have demonstrated that the expression of ncRNAs is

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