Differently expressed long noncoding RNAs and mRNAs in TK6 cells exposed to low dose hydroquinone.

Shaoyun Chen,Li Song,Yongmei Xiao,Jianming Peng,Hao Luo,Longmei Xu,Wen Chen,Gonghua Hu,Hairong Liang,Jiaxian Liu,Bei Lai,Hui Yang,Kairu Zhou,Zhidong Liu,Huanwen Tang

doi:10.18632/oncotarget.21481

Abstract

Previous studies have shown that long noncoding RNAs (lncRNAs) were related to human carcinogenesis and might be designated as diagnosis and prognosis biomarkers. Hydroquinone (HQ), as one of the metabolites of benzene, was closely relevant to occupational benzene poisoning and occupational leukemia. Using high-throughput sequencing technology, we investigated differences in lncRNA and mRNA expression profiles between experimental group (HQ 20 μmol/L) and control group (PBS). Compared to control group, a total of 65 lncRNAs and 186 mRNAs were previously identified to be aberrantly expressed more than two fold change in experimental group. To validate the sequencing results, we selected 10 lncRNAs and 10 mRNAs for quantitative real-time PCR (qRT-PCR). Through GO annotation and KEGG pathway analysis, we obtained 3 mainly signaling pathways, including P53 signaling pathway, which plays an important role in tumorigenesis and progression. After that, 25 lncRNAs and 32 mRNAs formed the lncRNA-mRNA co-expression network were implemented to play biological functions of the dysregulated lncRNAs transcripts by regulating gene expression. The lncRNAs target genes prediction provided a new idea for the study of lncRNAs. Finally, we have another important discovery, which is screened out 11 new lncRNAs without annotated. All these results uncovered that lncRNA and mRNA expression profiles in TK6 cells exposed to low dose HQ were different from control group, helping to further study the toxicity mechanisms of HQ and providing a new direction for the therapy of leukemia.

Highlights

Benzene is recognized as a human carcinogen, which is a widely used occupational harmful factor in industry [1]
All these results uncovered that long noncoding RNAs (lncRNAs) and mRNA expression profiles in TK6 cells exposed to low dose HQ were different from control group, helping to further study the toxicity mechanisms of HQ and providing a new direction for the therapy of leukemia
Expressed lncRNAs and mRNAs in TK6 cells exposed to low dose HQ

Summary

Introduction

Benzene is recognized as a human carcinogen, which is a widely used occupational harmful factor in industry [1]. The international agency for research on cancer confirms that benzene is a human cause of leukemia, and hematopoietic system is the target organ of benzene toxicity [2]. A case of acute myeloid leukemia (AML) caused by exposure to HQ for 16 years has been reported recently [3]. Several studies have reported that short-term exposure to HQ induced oxidative DNA damage and apoptosis [4]. Our previous research found that long-term exposure to HQ could result in transforming capability in vitro and the tumorigenesis capability in vivo [5]. Making an intensive study on the mechanisms of HQ toxicity is helpful for the early diagnosis and therapy of leukemia. There is an urgent need to improve early detection and identify new targets for therapy

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Discussion

Conclusion