Li Jin-Zhong, Ye Li-Hong, Wang De-Hua, Zhang Hai-Cong, Li Tao-Yuan, Liu Zhi-Quan, Dai Er-Hei, Li Min-Ran
Division of Infectious Disease, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Division of Pathology, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, China.
Virus Res. 2021 Jun;298:198405. doi: 10.1016/j.virusres.2021.198405. Epub 2021 Mar 26.
BACKGROUND/AIMS: To identify the inflammatory damage caused by chronic hepatitis B (CHB) in patients of chronic hepatitis B virus (HBV) infection complicated with non-alcoholic fatty liver disease (NAFLD), then guiding clinicians to carry out antiviral treatment.
According to the pathological features of liver biopsy, treatment-naïve obese patients of chronic HBV infection complicated with NAFLD who had elevated alanine transaminase (ALT) were divided into CHB group and NASH group. Transcriptome chips were used to analyze the expression profiles of long non-coding RNA (lncRNA) and mRNA in liver puncture tissues from the two groups. The chip data of CHB and NASH groups were analyzed for differential expression analysis, gene function analysis, signal pathway analysis, target gene prediction and competing endogenous RNAs (ceRNA) network analysis.
By comparing CHB group with NASH group, a total of 44 differentially expressed lncRNAs and 567 differentially expressed mRNAs were screened. GO analysis predicted that the differentially expressed mRNAs may affect monooxygenase activity and oxidoreductase activity. KEGG analysis predicted that the differentially expressed mRNAs may be related to signaling pathways involved in oxidative phosphorylation, phagosomes, and NAFLD. Differential analysis of lncRNA shown that the expression of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) in CHB group was significantly upregulated. Subsequently, through target gene prediction and ceRNA network analysis, we found thioredoxin interacting protein (TXNIP), which was significantly upregulated in the CHB group and had a ceRNA relationship with MALAT1. It is predicted that there may be a ceRNA regulation relationship of MALAT1/hsa-miR- 20b-5p/TXNIP.
The MALAT1/hsa-miR-20b-5p/TXNIP axis may mediate CHB-induced inflammatory damage in chronic HBV infection complicated with NAFLD, and the mechanism may be related to the activation of NLRP3 inflammatory bodies and downstream inflammatory responses.
背景/目的：识别慢性乙型肝炎病毒（HBV）感染合并非酒精性脂肪性肝病（NAFLD）患者中慢性乙型肝炎（CHB）所致的炎症损伤，从而指导临床医生进行抗病毒治疗。
根据肝活检的病理特征，将未经治疗的慢性HBV感染合并NAFLD且丙氨酸转氨酶（ALT）升高的肥胖患者分为CHB组和非酒精性脂肪性肝炎（NASH）组。使用转录组芯片分析两组肝穿刺组织中长链非编码RNA（lncRNA）和mRNA的表达谱。对CHB组和NASH组的芯片数据进行差异表达分析、基因功能分析、信号通路分析、靶基因预测和竞争性内源RNA（ceRNA）网络分析。
通过比较CHB组和NASH组，共筛选出44个差异表达的lncRNA和567个差异表达的mRNA。基因本体（GO）分析预测，差异表达的mRNA可能影响单加氧酶活性和氧化还原酶活性。京都基因与基因组百科全书（KEGG）分析预测，差异表达的mRNA可能与氧化磷酸化、吞噬体和NAFLD相关的信号通路有关。lncRNA差异分析显示，CHB组中肺癌转移相关转录本1（MALAT1）的表达显著上调。随后，通过靶基因预测和ceRNA网络分析，我们发现硫氧还蛋白相互作用蛋白（TXNIP）在CHB组中显著上调，且与MALAT1存在ceRNA关系。预测可能存在MALAT1/hsa-miR-20b-5p/TXNIP的ceRNA调控关系。
MALAT1/hsa-miR-20b-5p/TXNIP轴可能介导慢性HBV感染合并NAFLD中CHB诱导的炎症损伤，其机制可能与NLRP3炎性小体的激活及下游炎症反应有关。
