Long Non-Coding RNA and mRNA Expression Analysis in Liver of Mice With Clonorchis sinensis Infection.

Su Han,Jian Ding,Xiang Li,Li-Jiao Zuo,Xiao-Li Zhang,Rui Chen,Rui Chen,Bei-Bei Sun,Xu Jiang,Yan-Nan Gao,Shan-Shan Duan,Xin-Yi Hu,Xue-Li Zhang

doi:10.3389/fcimb.2021.754224

Abstract

Clonorchiasis is recognized as an important zoonotic parasitic disease worldwide. However, the roles of host long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the response to Clonorchis sinensis (C. sinensis) infection remain unknown. Here we compared the expression of lncRNAs and mRNAs in the liver tissue of mice infected with C. sinensis, in order to further understand the molecular mechanisms of clonorchiasis. A total of 388 lncRNAs and 1,172 mRNAs were found to be differentially expressed with absolute value of fold change (FC) ≥ 2.0 and p < 0.05 by microarray. Compared with controls, Gm6135 and 4930581F22Rik were the most over- and under-expressed lncRNAs; flavin-containing monooxygenase 3 (Fmo3) and deleted in malignant brain tumors 1 (Dmbt1) were the most over- and under-expressed mRNAs. Moreover, functional annotation showed that the significantly different mRNAs were related with “FOXO signaling pathway”, “Wnt signaling pathway”, and “AMPK signaling pathway”. Remarkably, lncRNA Gm8801 were significantly correlated with mRNA glycerol-3-phosphate acyltransferase mitochondrial (Gpam), insulin receptor substrate 2 (Irs2), and tumor necrosis factor receptor superfamily member 19 (Tnfrsf19) in ceRNA networks. These results showed that the expression profiles of lncRNAs and mRNAs in the liver changed after C. sinensis infection. Our results provided valuable insights into the lncRNAs and mRNAs involved in clonorchiasis pathogenesis, which may be useful for future control strategies.

Highlights

Clonorchiasis, caused by Clonorchis sinensis (C. sinensis), is an emerging zoonotic parasitic disease worldwide, distributed mainly in China, Korea, and northern Vietnam (Han et al, 2012; Lai et al, 2016)
The infected group and the control group clustered separately in the heat map (Figure 2). These results indicated that altered expressions of long non-coding RNA (lncRNA) and messenger RNA (mRNA) may play an important role in clonorchiasis
MRNA insulin receptor substrate 2 (Irs2) was decreased, while mRNA glycerol-3phosphate acyltransferase mitochondrial (Gpam) and Tnfrsf19 were increased at the same time point coinciding with the decrease of lncRNA protein phosphatase 1 (Gm8801) in the C. sinensis-infected group. These results indicated that mRNA Irs2 was positively correlated with lncRNA Gm8801, while mRNA Gpam and Tnfrsf19 were negatively correlated with Gm8801, which is consistent with the prediction

Summary

Introduction

Clonorchiasis, caused by Clonorchis sinensis (C. sinensis), is an emerging zoonotic parasitic disease worldwide, distributed mainly in China, Korea, and northern Vietnam (Han et al, 2012; Lai et al, 2016). Humans become infected by eating freshwater fish with C. sinensis metacercariae. Metacercariae exist in the small intestine and migrate via the ampulla of Vater to the biliary ducts (Lun et al, 2005). The adult fluke inhabits the biliary passages of humans and mammals and could cause epithelial hyperplasia of the biliary mucosa and even periductal fibrosis (Chung et al, 2004). Clinical manifestations of clonorchiasis vary from asymptomatic infections to severe morbidity and mortality, including epithelial hyperplasia, cholecystitis, periductal fibrosis, hepatic fibrosis, and cholangiocarcinoma (Keiser and Utzinger, 2005). We found that hepatic apoptosis and iron overload were involved in clonorchiasis (Han et al, 2017). The mechanism of liver/biliary injury, and whether other regulatory mechanisms or other small molecules are involved, remains unclear. Exploring the molecular mechanisms underlying clonorchiasis may contribute to the development of prevention measures and targeted drugs

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Results

Conclusion