Identification and characterization of interferon signaling-related microRNAs in occult hepatitis B virus infection

Wang, Yiying; Zhu, Ping; Qiu, Jing; Wang, Jie; Zhu, Huijuan; Zhu, Yinwei; Zhang, Lige; Zhu, Jie; Liu, Xingxiang; Dong, Chen

doi:10.1186/s13148-017-0404-9

Cited by 15 publications

(15 citation statements)

References 25 publications

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“…In patients with OBI, it has been found that the substitution of G-to-A at position 458 of the surface gene interferes with the splicing of S gene mRNA and was associated with a lack of HBsAg expression and low replication of HBV DNA. 29 Some early data suggested that micro-RNAs may play a role in OBI, as decreased serum miR-122 level and increased miR-130a level were found significantly associated with OBI 30 ; combing miR-122 and miR-130a may potentially serve as a surrogate algorithm to diagnose. Another pilot study of a 4-serum miRNA signature, which includes let-7c, miR-23b, miR-122, and miR-150, shows a high level of accuracy in discriminating OBI cases from the non-infected controls with an accuracy of more than 99%.…”

Section: Virologic and Molecular Mechanisms Of Obi Virologic Mechanismsmentioning

confidence: 99%

Current Knowledge of Occult Hepatitis B Infection and Clinical Implications

Yip

Wong

2019

Semin Liver Dis

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Occult hepatitis B infection (OBI) is a status of undetectable serum hepatitis B surface antigen (HBsAg) yet detectable serum and/or intrahepatic hepatitis B virus (HBV) DNA. Mutations in the preS1, preS2, and S regions of the HBsAg gene may result in undetectable HBsAg. OBI may either result from a self-limiting acute hepatitis, or in patients with chronic hepatitis B who achieved HBsAg seroclearance, which refers to the loss of detectability of serum HBsAg with or without antibody to HBsAg (anti-HBs) in chronic hepatitis B (CHB) patients. HBsAg seroclearance contributes to a significant proportion of population in seropositive OBI. Both spontaneous and antiviral treatment-induced HBsAg seroclearance rarely happens; yet both types of HBsAg seroclearance are durable. CHB patients who achieve HBsAg seroclearance generally have a favorable clinical course. There is still a low yet definite risk of HCC occurrence, particularly in male CHB patients who achieve HBsAg seroclearance after being 50 years old. Clinical implications of OBI include occurrence of cirrhosis and HCC, liver transplantation, blood products transfusion, hemodialysis, and so on. A potentially life-threatening condition would be OBI reactivation in patients during immunosuppression therapy, especially in the setting of intensified immunosuppression including in onco-hematological patients (those receiving hematopoietic stem cell transplantation and treated with the anti-CD20 monoclonal antibody [e.g., rituximab]). With more new insights into these two conditions, CHB patients who achieved HBsAg seroclearance generally have benign clinical course and good prognosis. Sensitive assay for serum HBV DNA should be considered to establish the presence of OBI in the clinical settings mentioned earlier, which will affect the management plan.

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Section: Virologic and Molecular Mechanisms Of Obi Virologic Mechanismsmentioning

confidence: 99%

Current Knowledge of Occult Hepatitis B Infection and Clinical Implications

Yip

Wong

2019

Semin Liver Dis

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“…Although research regarding the expression levels and associated functions of miRNA-122 in HCC and other liver diseases have been widely carried out (15,28), the reports are diffuse and contradictory. For example, miRNA-122 acted as a cancer suppressor gene and was downregulated in HCC tissues and cells compared with the adjacent normal tissues and normal cell lines (15,29), which was in line with the results of TCGA analysis.…”

Section: Discussionmentioning

confidence: 99%

Clinical value of miRNA‑122 in the diagnosis and prognosis of various types of cancer

2019

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The present study aimed to systematically analyze the value of microRNA-122 (miRNA-122) in the diagnosis and prognosis of hepatocellular carcinoma (HCC) and other types of cancer. First, the reverse transcription-quantitative polymerase chain reaction method was used to detect the expression levels of miRNA-122 in the serum samples of patients with HCC, benign lesions and healthy volunteers. Next, miRNA-seq data of miRNA-122 from The Cancer Genome Atlas database were used to analyze the differential expression and overall survival rate associated with a variety of types of cancer. Meanwhile, the target gene prediction of miRNA-122 was performed using four different software programs. Finally, 353 significant target genes were identified for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis. Finally, it was demonstrated that the expression levels of miRNA-122 in the HCC group were increased compared with the healthy group (P<0.001), but decreased with respect to the benign group (P<0.001). In addition, the combination of the miRNA-122 and a fetoprotein may further improve the diagnostic accuracy between the HCC and healthy groups (area under the curve, 0.980; 95% confidence interval, 0.958–1.000). It was also demonstrated that miRNA-122 exhibited significantly differential expression and the overall survival rate was predicted for various other types of cancer, including colorectal cancer, renal carcinoma, cholangiocarcinoma, prostate cancer and thyroid carcinoma. Functional enrichment analysis demonstrated that the target genes of miRNA-122 may contribute to the composition of the nucleus and cytoplasm, and regulate a variety of biological processes, including cardiac muscle cell differentiation and glucose metabolic processes via protein biosynthesis, estrogen and glucagon associated signaling pathways. These results revealed that miRNA-122 may be an indispensable biomarker for the diagnosis, prognostic evaluation and targeted therapy in pan-cancer.

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“…Compared to HCs, miR‐122 was significantly downregulated, while miR‐130a was significantly upregulated in OBI. Moreover, miR‐122 and miR‐130a could also discriminate OBI from HCs, ASC, and CHB (≥0.87 of AUC) . However, the differential expression of these miRNAs was not found in our study.…”

Section: Discussionmentioning

confidence: 99%

“…But it could reduce HBV pregenomic RNA encapsidation and capsid assembly . However, little information is available about miRNAs engaged in OBI and the regulatory mechanisms of these miRNAs remain largely unknown …”

Section: Introductionmentioning

confidence: 99%

“…14 However, little information is available about miRNAs engaged in OBI and the regulatory mechanisms of these miRNAs remain largely unknown. 15,16 In this study, miRNA sequencing was performed to systematically identify differentially expressed plasma miRNAs in OBI versus healthy controls (HCs). Then, five of these differentially expressed miRNAs ware further confirmed by quantitative reverse transcription real-time polymerase chain reaction (qRT-PCR).…”

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confidence: 99%

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Circulating miRNA expression profile and bioinformatics analysis in patients with occult hepatitis B virus infection

Hao

Wang

Xia

et al. 2019

Journal of Medical Virology

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Emerging suggest that microRNAs (miRNAs) play vital roles in the occurrence and development of hepatitis B virus (HBV) infectious disease. However, miRNAs in occult hepatitis B virus infection (OBI), a special stage of HBV infection, remain largely unknown. Herein, we conducted this study to identify differentially expressed miRNAs and then to investigate the potential roles of these miRNAs in OBI. Plasma miRNA expression profiles of three OBI patients and three healthy controls were analyzed with high through‐put miRNA sequencing technology. Altered expression of miRNAs was further confirmed with reverse transcription quantitative polymerase chain reaction (qRT‐PCR). Finally, bioinformatics analysis was conducted to investigate the involved pathways and target genes for these differentially expressed miRNAs. Totally, 32 differentially expressed miRNAs were identified between OBI and healthy controls by miRNA sequencing (fold change ≥ 1.5, P < .1, and counts per million reads ≥ 1), including 16 downregulated and 16 upregulated miRNAs. Differential expression of hsa‐miR‐486‐5p, ‐25‐3p, and ‐92a‐3p and ‐1‐3p was further validated by qRT‐PCR analysis, which was consistent with miRNA sequencing analysis. Moreover, these four miRNAs might distinguish OBI from HCs efficiently. Bioinformatics analyses indicated that the differentially expressed miRNAs were primarily involved in various biological processes related to gene expression and transcription, cell development and metabolism, protein modification and kinase activity regulation, as well as multiple signaling pathways such as PI3K/Akt signaling pathway. This study provided a global view of miRNA expression in plasma from OBI patients. These differentially expressed miRNAs might play important roles in the development of OBI, which provided intriguing insights into the screening and molecular mechanism of OBI.

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Identification and characterization of interferon signaling-related microRNAs in occult hepatitis B virus infection

Cited by 15 publications

References 25 publications

Current Knowledge of Occult Hepatitis B Infection and Clinical Implications

Current Knowledge of Occult Hepatitis B Infection and Clinical Implications

Clinical value of miRNA‑122 in the diagnosis and prognosis of various types of cancer

Circulating miRNA expression profile and bioinformatics analysis in patients with occult hepatitis B virus infection

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