|
1
|
Sartorius K, Wang Y, Sartorius B, Antwi SO, Li X, Chuturgoon A, Yu C, Lu Y, Wang Y. The interactive role of microRNA and other non-coding RNA in hepatitis B (HBV) associated fibrogenesis. Funct Integr Genomics 2025; 25:24. [PMID: 39847120 DOI: 10.1007/s10142-024-01519-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/27/2024] [Accepted: 12/27/2024] [Indexed: 01/24/2025]
Abstract
One of the outstanding features of chronic hepatitis B infection (CHB) is its strong association with liver fibrosis. CHB induced inflammation and injury trigger multiple biochemical and physical changes that include the promotion of a wide range of cytokines, chemokines and growth factors that activate hepatic stellate cells (HSCs) CHB induced activation of hepatic stellate cells (HSCs) is regarded as a central event in fibrogenesis to directly promote the synthesis of myofibroblasts and the expression of a range of materials to repair injured liver tissue. Fibrogenesis is modulated by the mainstream epigenetic machinery, as well as by non-coding RNA (ncRNA) that are often referred to as an ancillary epigenetic response to fine tune gene expression. Although extensive research has explained the regulatory role of ncRNA in liver fibrogenesis, most of this research relates to non-CHB etiologies. This review paper outlines the complex interactive regulatory role of microRNA (miRNA) and their interaction with long non-coding RNA (lncRNA), circular RNA (circRNA) and the mainstream epigenetic machinery in CHB induced liver fibrosis. The paper also illustrates some of the difficulties involved in translating candidate ncRNA into approved drugs or diagnostic tools. In conclusion, the important regulatory role of ncRNA in CHB induced liver fibrosis warrants further investigation to exploit their undoubted potential as diagnostic and therapeutic agents.
Collapse
Affiliation(s)
- Kurt Sartorius
- Faculty of Commerce, Law and Management, University of the Witwatersrand, Johannesburg, South Africa.
- Africa Hepatobiliarypancreato Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, AL, USA.
| | - Yanglong Wang
- Department of General Surgery, Xinyi People's Hospital, Xinyi, Jiangsu, China
| | - Benn Sartorius
- School of Public Health, University of Queensland, Brisbane, Australia
| | - Samuel O Antwi
- Africa Hepatobiliarypancreato Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, AL, USA
- Division of Epidemiology Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, AL, USA
| | - Xiaodong Li
- Africa Hepatobiliarypancreato Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, AL, USA
| | - Anil Chuturgoon
- School of Laboratory Medicine and Molecular Sciences, UKZN, Durban, South Africa
| | - Chongyuan Yu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yunjie Lu
- Africa Hepatobiliarypancreato Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, AL, USA.
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
| | - Yu Wang
- Department of Hepatobiliary Surgery, Jintan Affiliated Hospital of Jiangsu University, 213200, Changzhou, Jiangsu, China.
| |
Collapse
|
|
2
|
Kesheh MM, Bayat M, Kobravi S, Lotfalizadeh MH, Heydari A, Memar MY, Baghi HB, Kermanshahi AZ, Ravaei F, Taghavi SP, Zarepour F, Nahand JS, Hashemian SMR, Mirzaei H. MicroRNAs and human viral diseases: A focus on the role of microRNA-29. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167500. [PMID: 39260679 DOI: 10.1016/j.bbadis.2024.167500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 06/01/2024] [Accepted: 08/01/2024] [Indexed: 09/13/2024]
Abstract
The viral replication can impress through cellular miRNAs. Indeed, either the antiviral responses or the viral infection changes through cellular miRNAs resulting in affecting many regulatory signaling pathways. One of the microRNA families that is effective in human cancers, diseases, and viral infections is the miR-29 family. Members of miR-29 family are effective in different viral infections as their roles have appeared in regulation of immunity pathways either in innate immunity including interferon and inflammatory pathways or in adaptive immunity including activation of T-cells and antibodies production. Although miR-29a affects viral replication by suppressing antiviral responses, it can inhibit the expression of viral mRNAs via binding to their 3'UTR. In the present work, we discuss the evidence related to miR-29a and viral infection through host immunity regulation. We also review roles of other miR-29 family members by focusing on their role as biomarkers for diagnosing and targets for viral diseases management.
Collapse
Affiliation(s)
- Mina Mobini Kesheh
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mobina Bayat
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sepehr Kobravi
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tehran Azad University, Tehran, Iran
| | | | - Azhdar Heydari
- Physiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran; Department of Physiology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammad Yousef Memar
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Bannazadeh Baghi
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Atefeh Zamani Kermanshahi
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Ravaei
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Seyed Pouya Taghavi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Fatemeh Zarepour
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Javid Sadri Nahand
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Seyed Mohammad Reza Hashemian
- Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
| |
Collapse
|
|
3
|
Ling H, Wang XC, Liu ZY, Mao S, Yang JJ, Sha JM, Tao H. Noncoding RNA network crosstalk in organ fibrosis. Cell Signal 2024; 124:111430. [PMID: 39312989 DOI: 10.1016/j.cellsig.2024.111430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 09/12/2024] [Accepted: 09/19/2024] [Indexed: 09/25/2024]
Abstract
Fibrosis is a process involving excessive accumulation of extracellular matrix components, the severity of which interferes with the function of the organ in question. With the advances in RNA sequencing and in-depth molecular studies, a large number of current studies have pointed out the irreplaceable role of non-coding RNAs (ncRNAs) in the pathophysiological development of organ fibrosis. Here, by summarizing the results of a large number of studies on the interactions between ncRNAs, some studies have found that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), among others, are able to act as sponges or decoy decoys for microRNAs (miRNAs), act as competing endogenous RNAs (ceRNAs) to regulate the expression of miRNAs, and subsequently act on different mRNA targets, playing a role in the development of fibrosis in a wide variety of organs, including the heart, liver, kidneys, and spleen. parenchymal organs, including heart, liver, kidney, and spleen, play important roles in the development of fibrosis. These findings elucidate the intricate involvement of the lncRNA/circRNA-miRNA-mRNA axis in the pathophysiological processes underpinning organ fibrosis, thereby enhancing our comprehension of the onset and progression of this condition. Furthermore, they introduce novel potential therapeutic targets within the realm of ncRNA-based therapeutics, offering avenues for the development of innovative drugs aimed at mitigating or reversing the effects of organ fibrosis.
Collapse
Affiliation(s)
- Hui Ling
- Department of Thoracic Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China
| | - Xian-Chen Wang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China
| | - Zhi-Yan Liu
- Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China
| | - Sui Mao
- Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China
| | - Jing-Jing Yang
- Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
| | - Ji-Ming Sha
- Department of Thoracic Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
| | - Hui Tao
- Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
| |
Collapse
|
|
4
|
Kouroumalis E, Tsomidis I, Voumvouraki A. Extracellular Vesicles in Viral Liver Diseases. Viruses 2024; 16:1785. [PMID: 39599900 PMCID: PMC11598962 DOI: 10.3390/v16111785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/12/2024] [Accepted: 11/15/2024] [Indexed: 11/29/2024] Open
Abstract
Extracellular vesicles (EVs) are bilayer vesicles released by cells in the microenvironment of the liver including parenchymal and non-parenchymal cells. They are the third important mechanism in the communications between cells, besides the secretion of cytokines and chemokines and the direct cell-to-cell contact. The aim of this review is to discuss the important role of EVs in viral liver disease, as there is increasing evidence that the transportation of viral proteins, all types of RNA, and viral particles including complete virions is implicated in the pathogenesis of both viral cirrhosis and viral-related hepatocellular carcinoma. The biogenesis of EVs is discussed and their role in the pathogenesis of viral liver diseases is presented. Their use as diagnostic and prognostic biomarkers is also analyzed. Most importantly, the significance of possible novel treatment strategies for liver fibrosis and hepatocellular carcinoma is presented, although available data are based on experimental evidence and clinical trials have not been reported.
Collapse
Affiliation(s)
- Elias Kouroumalis
- Laboratory of Gastroenterology and Hepatology, University of Crete Medical School, 71500 Heraklion, Greece;
| | - Ioannis Tsomidis
- Laboratory of Gastroenterology and Hepatology, University of Crete Medical School, 71500 Heraklion, Greece;
| | - Argyro Voumvouraki
- 1st Department of Internal Medicine, AHEPA University Hospital, 54621 Thessaloniki, Greece;
| |
Collapse
|
|
5
|
da Silva LL, Leon LAA, da Cruz Moreira O, da Costa Nunes Pimentel Coelho WL, da Costa VD, Ivantes CAP, Pollo-Flores P, Lewis-Ximenez LL, de Paula VS, Villar LM. Serum microRNA 143 and 223 Gene Expression Profiles as Potential Biomarkers in Individuals with Hepatitis and COVID-19. Viruses 2024; 16:1734. [PMID: 39599849 PMCID: PMC11598994 DOI: 10.3390/v16111734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 10/25/2024] [Accepted: 10/28/2024] [Indexed: 11/29/2024] Open
Abstract
MicroRNAs (miRNAs) can act as biomarkers and descriptors of the association between infections and other diseases, such as hepatitis and COVID-19. This study aims to investigate the role of miRNA serum expression according to laboratory data concerning hepatitis and COVID-19. Seventy individuals recruited in Southern and Southeastern Brazil donated serum samples and were divided into four groups: (i) 20 negative subjects, (ii) 20 presenting hepatitis, (iii) 19 with COVID-19 and (iv) 11 with hepatitis and COVID-19. Three miRNAs (miR-122, miR-143 and miR-223) were evaluated using real-time PCR. Hematological and biochemical markers were also analyzed. MiR-143 and miR-223 were downregulated among the hepatitis/COVID-19 group (p < 0.05). A positive correlation was observed between miR-223 and lymphocytes. There was a negative correlation between alanine transaminase (ALT) and aspartate transaminase (AST) for miR-143 and miR-223 and gamma-glutamyl transferase (GGT), alkaline phosphatase (AP) and neutrophil/lymphocyte ratio (NLR) only for miR-223 (p < 0.05). For hepatic fibrosis (FIB-4), miR-122 and miR-143 had a greater association and miR-223 was more associated with a history of vaccination against COVID-19. MicroRNAs 143 and 223 could be useful as biomarkers for hepatitis coinfection with COVID-19.
Collapse
Affiliation(s)
- Lucas Lima da Silva
- National Reference Laboratory for Viral Hepatitis, Institute Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, Brazil; (V.D.d.C.); (L.L.L.-X.)
| | - Luciane Almeida Amado Leon
- Technological Development Laboratory, Institute Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, Brazil; (L.A.A.L.); (W.L.d.C.N.P.C.)
| | - Otacílio da Cruz Moreira
- Molecular Virology and Parasitology Laboratory, Institute Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, Brazil; (O.d.C.M.); (V.S.d.P.)
| | | | - Vanessa Duarte da Costa
- National Reference Laboratory for Viral Hepatitis, Institute Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, Brazil; (V.D.d.C.); (L.L.L.-X.)
| | | | - Priscila Pollo-Flores
- Department of Clinical Medicine, Fluminense Federal University, Niterói 24220-000, RJ, Brazil;
| | - Lia Laura Lewis-Ximenez
- National Reference Laboratory for Viral Hepatitis, Institute Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, Brazil; (V.D.d.C.); (L.L.L.-X.)
| | - Vanessa Salete de Paula
- Molecular Virology and Parasitology Laboratory, Institute Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, Brazil; (O.d.C.M.); (V.S.d.P.)
| | - Livia Melo Villar
- National Reference Laboratory for Viral Hepatitis, Institute Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, RJ, Brazil; (V.D.d.C.); (L.L.L.-X.)
| |
Collapse
|
|
6
|
Sutradhar PR, Sultana N, Nessa A. miRNA-221: A Potential Biomarker of Progressive Liver Injury in Chronic Liver Disease (CLD) due to Hepatitis B Virus (HBV) and Nonalcoholic Fatty Liver Disease (NAFLD). Int J Hepatol 2024; 2024:4221368. [PMID: 39185365 PMCID: PMC11343628 DOI: 10.1155/2024/4221368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 07/18/2024] [Indexed: 08/27/2024] Open
Abstract
Background: Early detection of progressive liver damage in chronic liver disease (CLD) patients is crucial for better treatment response. Several studies have shown the association of microRNA (miRNA) in the progression of CLD in regulating cell proliferation, fibrosis, and apoptosis as well as in carcinogenesis. Objectives: The study was aimed at determining the expression of miRNA-221 among different stages of fibrosis in CLD patients due to hepatitis B virus (HBV) and nonalcoholic fatty liver disease (NAFLD) and thus evaluate its role as an early biomarker in CLD. Methods: A total of 100 participants (75 CLD patients and 25 healthy control) were recruited in this cross-sectional study and divided into four groups, of which 25 as healthy control, 25 in CLD without fibrosis, 25 were CLD with fibrosis, and 25 were CLD with cirrhosis. Total RNA was extracted from plasma followed by cDNA synthesis, and finally, the expression of miRNA-221 was analyzed for its diagnostic potential as a single biomarker using the qRT-PCR method. Results: The plasma level of miRNA-221 was significantly upregulated in different fibrosis stages of CLD (p < 0.05), and this upregulation was positively correlated with the progression of fibrosis (p < 0.05). Significantly increased expression of miRNA-221 was found in NAFLD patients compared to HBV patients in the CLD without fibrosis patient group (p < 0.05), while expression of miRNA-221 was significantly upregulated among HBV patients in the CLD with the fibrosis group. miRNA-221 showed high diagnostic accuracy in discriminating different stages of fibrosis from healthy control (p < 0.05). Conclusion: miRNA-221 may be used as a potential plasma biomarker for early prediction of fibrosis progression in CLD patients.
Collapse
Affiliation(s)
- Parthana Rani Sutradhar
- Department of MicrobiologySher-E-Bangla Medical College (SBMC), Barishal, Bangladesh
- Department of VirologyBangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh
| | - Nahida Sultana
- Department of VirologyBangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh
| | - Afzalun Nessa
- Department of VirologyBangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh
| |
Collapse
|
|
7
|
Suzuki T, Matsuura K, Nagura Y, Ito K, Ogawa S, Kawamura H, Fujiwara K, Nagaoka K, Iio E, Watanabe T, Kataoka H, Tanaka Y. MicroRNA-223-3p levels in serum-derived extracellular vesicles predict regression of M2BPGi-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents. J Gastroenterol 2024; 59:719-731. [PMID: 38739200 DOI: 10.1007/s00535-024-02115-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 05/02/2024] [Indexed: 05/14/2024]
Abstract
BACKGROUND We retrospectively investigated microRNA (miRNA) levels in serum-derived extracellular vesicles (EVs) as predictive indicators for regression of liver fibrosis, after achievement of a sustained virological response (SVR) by direct-acting antiviral (DAA) therapy for chronic hepatitis C (CHC). METHODS The study subjects were recruited from a historical cohort of 108 CHC patients whose pretreatment serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels were ≥ 2.0 cut-off index (COI). We classified patients with M2BPGi levels < 1.76 and ≥ 1.76 COI at 2 years after the end of treatment (EOT) into the regression and non-regression groups, respectively. Eleven of the patients were assigned to the discovery set, and we comprehensively investigated the miRNAs contained in serum-derived EVs at 24 weeks after the EOT (EOT24W), using RNA sequencing. The remaining 97 patients were assigned to the validation set, and reproducibility was verified by quantitative real-time PCR. RESULTS Through analysis of the discovery and validation sets, we identified miR-223-3p and miR-1290 as candidate predictors. Subsequently, we analyzed various clinical data, including these candidate miRNAs. Multivariate analyses revealed that the levels of miR-223-3p at EOT24W were significantly associated with regression of M2BPGi-based liver fibrosis (Odds ratio: 1.380; P = 0.024). Consistent results were obtained, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis (pretreatment M2BPGi levels ≥ 3.3 COI). CONCLUSIONS The miR-223-3p level in serum-derived EVs at EOT24W is a feasible predictor of regression of M2BPGi-based liver fibrosis after achievement of an SVR by DAA therapy.
Collapse
Affiliation(s)
- Takanori Suzuki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan.
| | - Yoshihito Nagura
- Department of Gastroenterology, Kasugai Municipal Hospital, Kasugai, Japan
| | - Kyoko Ito
- Department of Virology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shintaro Ogawa
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hayato Kawamura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan
| | - Kei Fujiwara
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan
| | - Katsuya Nagaoka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Etsuko Iio
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Takehisa Watanabe
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| |
Collapse
|
|
8
|
Xue X, Li Y, Yao Y, Zhang S, Peng C, Li Y. A comprehensive review of miR-21 in liver disease: Big impact of little things. Int Immunopharmacol 2024; 134:112116. [PMID: 38696909 DOI: 10.1016/j.intimp.2024.112116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/10/2024] [Accepted: 04/17/2024] [Indexed: 05/04/2024]
Abstract
microRNAs (miRNAs), a class of non-coding RNA with 20-24 nucleotides, are defined as the powerful regulators for gene expression. miR-21 is a multifunctional miRNA enriched in the circulatory system and multiple organs, which not only serves as a non-invasive biomarker in disease diagnosis, but also participates in many cellular activities. In various chronic liver diseases, the increase of miR-21 affects glycolipid metabolism, viral infection, inflammatory and immune cell activation, hepatic stellate cells activation and tissue fibrosis, and autophagy. Moreover, miR-21 is also a liaison in the deterioration of chronic liver disease to hepatocellular carcinoma (HCC), and it impacts on cell proliferation, apoptosis, migration, invasion, angiogenesis, immune escape, and epithelial-mesenchymal transformation by regulating target genes expression in different signaling pathways. In current research on miRNA therapy, some natural products can exert the hepatoprotective effects depending on the inhibition of miR-21 expression. In addition, miR-21-based therapeutic also play a role in regulating intracellular miR-21 levels and enhancing the efficacy of chemotherapy drugs. Herein, we systemically summarized the recent progress of miR-21 on biosynthesis, biomarker function, molecular mechanism and miRNA therapy in chronic liver disease and HCC, and looked forward to outputting some information to enable it from bench to bedside.
Collapse
Affiliation(s)
- Xinyan Xue
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yanzhi Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yuxin Yao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Shenglin Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Yunxia Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| |
Collapse
|
|
9
|
Bera C, Hamdan-Perez N, Patel K. Non-Invasive Assessment of Liver Fibrosis in Hepatitis B Patients. J Clin Med 2024; 13:1046. [PMID: 38398358 PMCID: PMC10889471 DOI: 10.3390/jcm13041046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 02/02/2024] [Accepted: 02/08/2024] [Indexed: 02/25/2024] Open
Abstract
The aim of this review is to provide updated information on the clinical use of non-invasive serum and imaging-based tests for fibrosis assessment in chronic hepatitis B (CHB) virus infection. In recent years, non-invasive tests (NIT) have been increasingly used to determine eligibility for treatment. Liver biopsy is still considered the gold standard for assessing inflammatory activity and fibrosis staging, but it is an invasive procedure with inherent limitations. Simple serum markers such as APRI and FIB-4 are limited by indeterminate results but remain useful initial tests for fibrosis severity if imaging elastography is not available. Point-of-care US-based elastography techniques, such as vibration-controlled transient elastography or 2D shear wave elastography, are increasingly available and have better accuracy than simple serum tests for advanced fibrosis or cirrhosis, although stiffness cut-offs are variable based on E-antigen status and inflammatory activity. Current NITs have poor diagnostic performance for following changes in fibrosis with antiviral therapy. However, NITs may have greater clinical utility for determining prognosis in patients with CHB that have advanced disease, especially for the development of hepatocellular carcinoma and/or liver decompensation. Algorithms combining serum and imaging NITs appear promising for advanced fibrosis and prognostic risk stratification.
Collapse
Affiliation(s)
- Chinmay Bera
- Division of Gastroenterology, University Health Network Toronto, Toronto General Hospital, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada; (N.H.-P.)
| | | | | |
Collapse
|
|
10
|
Jiang T, Leng W, Zhong S. Diagnostic Role of Circulating miRNAs in the Grading of Chronic Hepatitis B-Related Liver Fibrosis: A Systematic Review and Meta-Analysis. Lab Med 2023; 54:479-488. [PMID: 36637253 DOI: 10.1093/labmed/lmac151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
OBJECTIVE miRNAs are considered potential biomarkers that can be used for the grading of chronic hepatitis B (CHB)-related liver fibrosis. This meta-analysis aims to elucidate the diagnostic performance of miRNAs. METHODS Databases were used to search for meta-analyses. A bivariate model was used to calculate pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). In addition, the area under the summary receiver operating characteristic curve (AUC) and 95% confidence intervals (CIs) were calculated. RESULTS A total of 9 studies with 1159 patients with CHB-related liver fibrosis were assessed. For diagnosis of significant liver fibrosis, the pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.73 (95% CI, 0.68-0.78), 0.78 (95% CI, 0.70-0.84), 3.32 (95% CI, 2.52-4.37), 0.34 (95% CI, 0.30-0.39), 9.70 (95% CI, 7.10-13.24), and 0.81 (95% CI, 0.77-0.84), respectively. CONCLUSION miRNAs are potential biomarkers of CHB-related liver fibrosis.
Collapse
Affiliation(s)
- Ting Jiang
- Department of Infectious Disease, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Infectious Disease, Chengdu First People's Hospital, Chengdu, China
| | - Wenying Leng
- Emergency Department, Chengdu First People's Hospital, Chengdu, China
| | - Sen Zhong
- Department of Infectious Disease, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| |
Collapse
|
|
11
|
Doghish AS, Elballal MS, Elazazy O, Elesawy AE, Elrebehy MA, Shahin RK, Midan HM, Sallam AAM. The role of miRNAs in liver diseases: Potential therapeutic and clinical applications. Pathol Res Pract 2023; 243:154375. [PMID: 36801506 DOI: 10.1016/j.prp.2023.154375] [Citation(s) in RCA: 67] [Impact Index Per Article: 33.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/10/2023] [Accepted: 02/11/2023] [Indexed: 02/16/2023]
Abstract
MicroRNAs (miRNAs) are a class of short, non-coding RNAs that function post-transcriptionally to regulate gene expression by binding to particular mRNA targets and causing destruction of the mRNA or translational inhibition of the mRNA. The miRNAs control the range of liver activities, from the healthy to the unhealthy. Considering that miRNA dysregulation is linked to liver damage, fibrosis, and tumorigenesis, miRNAs are a promising therapeutic strategy for the evaluation and treatment of liver illnesses. Recent findings on the regulation and function of miRNAs in liver diseases are discussed, with an emphasis on miRNAs that are highly expressed or enriched in hepatocytes. Alcohol-related liver illness, acute liver toxicity, viral hepatitis, hepatocellular carcinoma, liver fibrosis, liver cirrhosis, and exosomes in chronic liver disease all emphasize the roles and target genes of these miRNAs. We briefly discuss the function of miRNAs in the etiology of liver diseases, namely in the transfer of information between hepatocytes and other cell types via extracellular vesicles. Here we offer some background on the use of miRNAs as biomarkers for the early prognosis, diagnosis, and assessment of liver diseases. The identification of biomarkers and therapeutic targets for liver disorders will be made possible by future research into miRNAs in the liver, which will also help us better understand the pathogeneses of liver diseases.
Collapse
Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Mohammed S Elballal
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Ola Elazazy
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Ahmed E Elesawy
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mahmoud A Elrebehy
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt.
| | - Reem K Shahin
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Heba M Midan
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Al-Aliaa M Sallam
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| |
Collapse
|
|
12
|
Chen Z, Ma Y, Cai J, Sun M, Zeng L, Wu F, Zhang Y, Hu M. Serum biomarkers for liver fibrosis. Clin Chim Acta 2022; 537:16-25. [PMID: 36174721 DOI: 10.1016/j.cca.2022.09.022] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 09/21/2022] [Accepted: 09/22/2022] [Indexed: 11/03/2022]
Abstract
Liver fibrosis is a common pathway in most chronic liver diseases, characterized by excessive extracellular matrix accumulation. Without treatment, fibrosis will ultimately result in cirrhosis, portal hypertension, and even liver failure. It is considered that liver fibrosis is reversible while cirrhosis is not, making it significant to diagnose and evaluate liver fibrogenesis timely. As the gold standard, liver biopsy is imperfect due to its invasiveness and sampling error. Therefore, attempts at uncovering noninvasive tests have become a hot topic in liver fibrosis. Nowadays, as an important category of noninvasive tests, serum biomarkers, which are safer, convenient, repeatable, and more acceptable, are widely discussed and commonly used in clinical practice. Serum biomarkers of liver fibrosis can be divided into class I (direct) and classⅡ (indirect) markers. However, the diagnostic efficiency still varies among studies. This article summarizes the most established and newly discovered serum biomarkers for hepatic fibrogenesis.
Collapse
Affiliation(s)
- Zhiyang Chen
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yichen Ma
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Jingyao Cai
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Mei Sun
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Ling Zeng
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Fengxi Wu
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yiru Zhang
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Min Hu
- Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
| |
Collapse
|
|
13
|
Liu C, Hou X, Mo K, Li N, An C, Liu G, Pan Z. Serum non-coding RNAs for diagnosis and stage of liver fibrosis. J Clin Lab Anal 2022; 36:e24658. [PMID: 35989522 PMCID: PMC9550980 DOI: 10.1002/jcla.24658] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 07/01/2022] [Accepted: 08/02/2022] [Indexed: 11/24/2022] Open
Abstract
Background All chronic liver diseases could lead to liver fibrosis. Accurate diagnosis and stage of fibrosis were important for the medical determination, management, and therapy. Liver biopsy was considered to be the gold criteria of fibrosis diagnosis. However, liver biopsy was an invasive method with some drawbacks. Non‐invasive tests for liver fibrosis included radiologic method and serum‐based test. Radiologic examination was influenced by obesity, cost, and availability. Serum‐based test was widely used in the screening and diagnostic of liver fibrosis. However, the accuracy was still needed to be improved. Methods Recent studies showed serum non‐coding RNAs: microRNA, long non‐coding RNA(lncRNA), and circular RNA(circRNA), which have the potentiality to be non‐invasive markers for liver fibrosis. The recent progress was summarized in this review. Results These studies showed serum non‐coding RNAs exerted a good diagnostic performance for liver fibrosis. A panel that included several non‐coding RNAs could increase the accuracy of single marker. Conclusions Serum microRNAs, lncRNAs, and circRNAs could be potential non‐invasive markers for diagnosis and stage of liver fibrosis. More high‐quality clinical study is needed for further research.
Collapse
Affiliation(s)
- Chao Liu
- Clinical Laboratory, Guang'anmen HospitalChina Academy of Chinese Medical SciencesBeijingChina
| | - Xueyun Hou
- Clinical Laboratory, Guang'anmen HospitalChina Academy of Chinese Medical SciencesBeijingChina
| | - Kaixin Mo
- Clinical Laboratory, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
| | - Nannan Li
- Clinical Laboratory, Guang'anmen HospitalChina Academy of Chinese Medical SciencesBeijingChina
| | - Cheng An
- Clinical Laboratory, Guang'anmen HospitalChina Academy of Chinese Medical SciencesBeijingChina
| | - Guijian Liu
- Clinical Laboratory, Guang'anmen HospitalChina Academy of Chinese Medical SciencesBeijingChina
| | - Zongdai Pan
- Clinical Laboratory, Guang'anmen HospitalChina Academy of Chinese Medical SciencesBeijingChina
| |
Collapse
|
|
14
|
Loukachov VV, van Dort KA, Maurer I, Takkenberg RB, de Niet A, Reesink HW, Willemse SB, Kootstra NA. Identification of Liver and Plasma microRNAs in Chronic Hepatitis B Virus infection. Front Cell Infect Microbiol 2022; 12:790964. [PMID: 35719345 PMCID: PMC9201251 DOI: 10.3389/fcimb.2022.790964] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 04/25/2022] [Indexed: 01/05/2023] Open
Abstract
Background and Aims With current standard of care a functional cure for Chronic Hepatitis B (CHB) is only achieved in 1-3% of patients and therefore novel therapies are needed. Disease activity during CHB can be determined by a broad range of virological biomarkers, however these biomarkers are also targets for novel treatment strategies. The aim of this study was to identify novel miRNAs that are differentially expressed in plasma and liver in CHB, and determine whether these miRNAs may serve as biomarkers of disease stage or treatment outcome. Methods miRNA Next-Generation-Sequencing of plasma and liver samples from CHB patient and controls was performed to identify differentially expressed miRNAs. The identified candidate miRNAs were validated by qPCR in additional plasma and liver samples from two CHB cohorts. Results Several miRNAs in plasma and liver were found to be differentially expressed between CHB patients and controls. Of the identified miRNAs expression levels of miR-122-5p in plasma were associated with plasma HBsAg, and plasma and liver HBV-DNA levels. Expression levels of miR-223-3p, miR-144-5p and miR-133a-3p in liver were associated with plasma alanine aminotransferase levels. No correlation was observed between miRNA expression levels at baseline and treatment outcome. Conclusions Limited overlap between plasma and liver miRNAs was found, indicating that plasma miRNAs could be useful as biomarkers for treatment outcome or viral activity during treatment. Whereas liver miRNAs are more likely to be regulated by HBV and could be potential therapeutic targets to control viral activity in liver.
Collapse
Affiliation(s)
- Vladimir V. Loukachov
- Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
- Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, Netherlands
| | - Karel A. van Dort
- Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
- Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, Netherlands
| | - Irma Maurer
- Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
- Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, Netherlands
| | - R. Bart Takkenberg
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers , University of Amsterdam, Amsterdam, Netherlands
| | - Anniki de Niet
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers , University of Amsterdam, Amsterdam, Netherlands
| | - Henk W. Reesink
- Department of Gastroenterology and Hepatology, Leids University Medical Center, Leiden, Netherlands
| | - Sophie B. Willemse
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers , University of Amsterdam, Amsterdam, Netherlands
| | - Neeltje A. Kootstra
- Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
- Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, Netherlands
- *Correspondence: Neeltje A. Kootstra,
| |
Collapse
|
|
15
|
Wang C, Liu J, Yan Y, Tan Y. Role of Exosomes in Chronic Liver Disease Development and Their Potential Clinical Applications. J Immunol Res 2022; 2022:1695802. [PMID: 35571570 PMCID: PMC9106457 DOI: 10.1155/2022/1695802] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 04/02/2022] [Accepted: 04/18/2022] [Indexed: 12/11/2022] Open
Abstract
Extracellular vesicles (EVs) are vesicular bodies (40-1000 nm) with double-layer membrane structures released by different cell types into extracellular environments, including apoptosis bodies, microvesicles, and exosomes. Exosomes (30-100 nm) are vesicles enclosed by extracellular membrane and contain effective molecules of secretory cells. They are derived from intracellular multivesicular bodies (MVBs) that fuse with the plasma membrane and release their intracellular vesicles by exocytosis. Research has shown that almost all human cells could secrete exosomes, which have a certain relationship with corresponding diseases. In chronic liver diseases, exosomes release a variety of bioactive components into extracellular spaces, mediating intercellular signal transduction and materials transport. Moreover, exosomes play a role in the diagnosis, treatment, and prognosis of various chronic liver diseases as potential biomarkers and therapeutic targets. Previous studies have found that mesenchymal stem cell-derived exosomes (MSC-ex) could alleviate acute and chronic liver injury and have the advantages of high biocompatibility and low immunogenicity. In this paper, we briefly summarize the role of exosomes in the pathogenesis of different chronic liver diseases and the latest research progresses of MSC-ex as the clinical therapeutic targets.
Collapse
Affiliation(s)
- Chen Wang
- The Third Hospital of Zhenjiang Affiliated Jiangsu University, Jiangsu University, Zhenjiang, 212005 Jiangsu, China
- School of Medicine, Jiangsu University, Zhenjiang, 212013 Jiangsu, China
| | - Jinwen Liu
- School of Medicine, Jiangsu University, Zhenjiang, 212013 Jiangsu, China
| | - Yongmin Yan
- School of Medicine, Jiangsu University, Zhenjiang, 212013 Jiangsu, China
| | - Youwen Tan
- The Third Hospital of Zhenjiang Affiliated Jiangsu University, Jiangsu University, Zhenjiang, 212005 Jiangsu, China
| |
Collapse
|
|
16
|
Perez-Sanchez C, Barbera Betancourt A, Lyons PA, Zhang Z, Suo C, Lee JC, McKinney EF, Modis LK, Ellson C, Smith KG. miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease. J Exp Med 2022; 219:e20211366. [PMID: 35363256 PMCID: PMC8980842 DOI: 10.1084/jem.20211366] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 12/23/2021] [Accepted: 02/17/2022] [Indexed: 02/02/2023] Open
Abstract
MicroRNAs are critical regulators of gene expression controlling cellular processes including inflammation. We explored their role in the pathogenesis of inflammatory bowel disease (IBD) and identified reduced expression of miR-374a-5p in IBD monocytes that correlated with a module of up-regulated genes related to the inflammatory response. Key proinflammatory module genes, including for example TNFα, IL1A, IL6, and OSM, were inversely correlated with miR-374a-5p and were validated in vitro. In colonic biopsies, miR-374a-5p was again reduced in expression and inversely correlated with the same inflammatory module, and its levels predicted subsequent response to anti-TNF therapy. Increased miR-374a-5p expression was shown to control macrophage-driven inflammation by suppressing proinflammatory mediators and to reduce the capacity of monocytes to migrate and activate T cells. Our findings suggest that miR-374a-5p reduction is a central driver of inflammation in IBD, and its therapeutic supplementation could reduce monocyte-driven inflammation in IBD or other immune-mediated diseases.
Collapse
Affiliation(s)
- Carlos Perez-Sanchez
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK
- Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK
- Rheumatology Service, Reina Sofia University Hospital, Maimonides Biomedical Research Institute of Córdoba, University of Cordoba, Cordoba, Spain
| | - Ariana Barbera Betancourt
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK
- Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK
| | - Paul A. Lyons
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK
- Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK
| | - Zinan Zhang
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK
- Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK
- Molecular Development of the Immune System Section, Laboratory of Immune System Biology and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
| | - Chenqu Suo
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK
- Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK
- Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
- Department of Paediatrics, Cambridge University Hospitals, Cambridge, UK
| | - James C. Lee
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK
- Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK
| | - Eoin F. McKinney
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK
- Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK
| | | | | | - Kenneth G.C. Smith
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK
- Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| |
Collapse
|
|
17
|
Gu J, Xu H, Chen Y, Li N, Hou X. MiR-223 as a Regulator and Therapeutic Target in Liver Diseases. Front Immunol 2022; 13:860661. [PMID: 35371024 PMCID: PMC8965842 DOI: 10.3389/fimmu.2022.860661] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Accepted: 02/23/2022] [Indexed: 12/20/2022] Open
Abstract
MicroRNAs (miRNAs) are endogenous non-coding single-stranded small molecule RNAs consisting of 20–24 nucleotides that are highly conserved in species evolution. Expression of miRNAs is strictly tissue-specific, and it is chronological in fungi and plants, as well as in animals. MiR-223 has been shown to play a key role in innate immunity, and dysregulation of its expression contributes to the pathogenesis of multiple inflammatory diseases, and cancers. In this article the biosynthesis and functions of miR-223 in innate immunity are reviewed, and the role of miR-223 in liver physiopathology and therapeutic prospects are highlighted.
Collapse
Affiliation(s)
- Jiarong Gu
- School of Medicine, Ningbo University, Ningbo, China
| | - Hao Xu
- School of Medicine, Ningbo University, Ningbo, China
| | - Yandong Chen
- School of Medicine, Ningbo University, Ningbo, China
| | - Na Li
- School of Medicine, Ningbo University, Ningbo, China
| | - Xin Hou
- School of Medicine, Ningbo University, Ningbo, China.,The Affiliated Hospital of Medical School, Ningbo University, Ningbo, China
| |
Collapse
|
|
18
|
Song M, Yang C. MiRNAs in liver fibrosis: new targets and opportunities for therapy. Microrna 2022:363-372. [DOI: 10.1016/b978-0-323-89774-7.00005-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
19
|
Yuan S, Wu Q, Wang Z, Che Y, Zheng S, Chen Y, Zhong X, Shi F. miR-223: An Immune Regulator in Infectious Disorders. Front Immunol 2021; 12:781815. [PMID: 34956210 PMCID: PMC8702553 DOI: 10.3389/fimmu.2021.781815] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 11/24/2021] [Indexed: 12/12/2022] Open
Abstract
MicroRNAs (miRNAs) are diminutive noncoding RNAs that can influence disease development and progression by post-transcriptionally regulating gene expression. The anti-inflammatory miRNA, miR-223, was first identified as a regulator of myelopoietic differentiation in 2003. This miR-223 exhibits multiple regulatory functions in the immune response, and abnormal expression of miR-223 is shown to be associated with multiple infectious diseases, including viral hepatitis, human immunodeficiency virus type 1 (HIV-1), and tuberculosis (TB) by influencing neutrophil infiltration, macrophage function, dendritic cell (DC) maturation and inflammasome activation. This review summarizes the current understanding of miR-223 physiopathology and highlights the molecular mechanism by which miR-223 regulates immune responses to infectious diseases and how it may be targeted for diagnosis and treatment.
Collapse
Affiliation(s)
- Shun Yuan
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Qi Wu
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zhiwei Wang
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yanjia Che
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Sihao Zheng
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yuanyang Chen
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xiaohan Zhong
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Feng Shi
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| |
Collapse
|
|
20
|
MicroRNA in refined diagnosis of choroidal melanoma. ACTA BIOMEDICA SCIENTIFICA 2021. [DOI: 10.29413/abs.2021-6.6-1.8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Epigenetic studies of the level of microRNAs in human oncogenesis indicate their signifi cant role in the development and growth of malignant tumors of various origins. The fi rst works on the role of microRNAs in patients with uveal melanoma appeared in 2008.The aim: to analyze the expression level of miRNA-126 and miRNA-223 in the plasma blood of patients and to determine their signifi cance in the refi ned diagnosis of choroidal melanoma. Materials and methods. We examined 84 patients with choroidal melanoma (CM), mean age – 63.4 ± 1.2 (35–86 y.o.). Localization – a single CM node with a thickness of 0.77–17.19 mm. The control group consisted of 28 volunteers, age – 62.9 ± 1.42 (45–78 y.o.). Plasma miRNA expression levels were determined by real-time PCR.Results. An increase in the level of expression of miRNA-223 and miRNA-126 in blood plasma was confi rmed in all 84 patients with choroidal melanoma N0M0 compared with the control group. An increase in the expression of miRNA-223 and miRNA-126 was proved with an increase in tumor prominence.Conclusion. The obtained results of an increase in the expression of miRNA-223 indicate an increase in cell proliferation, and an increase in the expression of miRNA-126 on the activation of angiogenesis in a growing tumor, which makes it possible to recommend a study of the level of miRNA-223 and miRNA-126 for a more accurate diagnosis of small CM in cases of difficulty of differential diagnosis with other tumor-like diseases of the choroid.
Collapse
|
|
21
|
Favero A, Segatto I, Perin T, Belletti B. The many facets of miR-223 in cancer: Oncosuppressor, oncogenic driver, therapeutic target, and biomarker of response. WILEY INTERDISCIPLINARY REVIEWS-RNA 2021; 12:e1659. [PMID: 33951281 PMCID: PMC8518860 DOI: 10.1002/wrna.1659] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/29/2021] [Accepted: 03/30/2021] [Indexed: 12/11/2022]
Abstract
Given their intrinsic pleiotropism, microRNAs (miR) play complex biological roles, in both normal and pathological conditions. Often the same miR can act as oncogene or oncosuppressor, depending on the biological process dysregulated in each specific tissue. miR‐223 does not represent an exception to this rule and its functions greatly differ in different contexts. miR‐223 has been widely studied in the hematopoietic compartment, where it plays a central role in innate immune response, regulating myeloid differentiation and granulocytes function. Accordingly, dysregulated expression of miR‐223 has been associated to different inflammatory disorders and tumors arising from the immune compartment. Most carcinomas, breast cancer being the most studied, display loss of miR‐223. However, in gastro‐esophageal cancers miR‐223 is frequently overexpressed and correlates with worse prognosis. A link between miR‐223 and response to CDK4/6‐inhibitors has been recently proposed, suggesting a role as biomarker of therapeutic response. The notion that one of the most commonly mutated protein in cancer, mutant p53, binds the promoter of miR‐223 and suppresses its transcription, adds a further level of complexity to the full understanding of miR‐223 in cancer. In this review, we will summarize the current knowledge on the molecular networks that alter or are altered by miR‐223, in different cancer types. We will discuss if the times are ready for the exploitation of miR‐223 as predictive biomarker of treatment response or, even, as therapeutic target, in specific settings. Finally, we will suggest which could be the next steps to be taken for a realistic clinical application of miR‐223. This article is categorized under:
RNA in Disease and Development > RNA in Disease
Collapse
Affiliation(s)
- Andrea Favero
- Molecular Oncology Unit, Centro di Riferimento Oncologico di Aviano (CRO Aviano), IRCCS, National Cancer Institute, Aviano, Italy
| | - Ilenia Segatto
- Molecular Oncology Unit, Centro di Riferimento Oncologico di Aviano (CRO Aviano), IRCCS, National Cancer Institute, Aviano, Italy
| | - Tiziana Perin
- Pathology Unit, Centro di Riferimento Oncologico di Aviano (CRO Aviano), IRCCS, National Cancer Institute, Aviano, Italy
| | - Barbara Belletti
- Molecular Oncology Unit, Centro di Riferimento Oncologico di Aviano (CRO Aviano), IRCCS, National Cancer Institute, Aviano, Italy
| |
Collapse
|
|
22
|
Shi Y, Du L, Lv D, Li Y, Zhang Z, Huang X, Tang H. Emerging role and therapeutic application of exosome in hepatitis virus infection and associated diseases. J Gastroenterol 2021; 56:336-349. [PMID: 33665710 PMCID: PMC8005397 DOI: 10.1007/s00535-021-01765-4] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 01/23/2021] [Indexed: 02/05/2023]
Abstract
Hepatitis viruses are chief pathogens of hepatitis and end-stage liver diseases. Their replication and related pathogenic process highly rely on the host micro-environment and multiple cellular elements, including exosomes. Representing with a sort of cell-derived vesicle structure, exosomes were considered to be dispensable cellular components, even wastes. Along with advancing investigation, a specific profile of exosome in driving hepatitis viruses' infection and hepatic disease progression is revealed. Exosomes greatly affect the pathogenesis of hepatitis viruses by mediating their replication and modulating the host immune responses. The characteristics of host exosomes are markedly changed after infection with hepatitis viruses. Exosomes released from hepatitis virus-infected cells can carry viral nucleic or protein components, thereby acting as an effective subterfuge for hepatitis viruses by participating in viral transportation and immune escape. On the contrary, immune cell-derived exosomes contribute toward the innate antiviral immune defense and virus eradication. There is growing evidence supporting the application of exosomal biomarkers for predicting disease progress or therapeutic outcome, while exosomal nanoshuttles are regarded as promising therapeutic options based on their delivery properties and immune compatibility. In this review, we summarize the biogenesis and secretion mechanism of exosomes, review the recent findings pertaining to the role of exosomes in the interplay between hepatitis viruses and innate immune responses, and conclude their potential in further therapeutic application.
Collapse
Affiliation(s)
- Ying Shi
- Center of Infectious Diseases, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
- School of Medicine, University of Electronic Science and Technology of China, No. 4 Section 2, North Jianshe Road, Chengdu, 610054, Sichuan, China
- Department of Hepatobiliary Surgery and Cell Transplantation Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, No. 32 Western Section 2, 1st Ring Rd., Chengdu, 610072, Sichuan, China
| | - Lingyao Du
- Center of Infectious Diseases, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, No. 17 People's South Road, Chengdu, 610041, Sichuan, China
| | - Duoduo Lv
- Center of Infectious Diseases, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, No. 17 People's South Road, Chengdu, 610041, Sichuan, China
| | - Yan Li
- School of Medicine, University of Electronic Science and Technology of China, No. 4 Section 2, North Jianshe Road, Chengdu, 610054, Sichuan, China
- Department of Hepatobiliary Surgery and Cell Transplantation Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, No. 32 Western Section 2, 1st Ring Rd., Chengdu, 610072, Sichuan, China
| | - Zilong Zhang
- School of Medicine, University of Electronic Science and Technology of China, No. 4 Section 2, North Jianshe Road, Chengdu, 610054, Sichuan, China
- Department of Hepatobiliary Surgery and Cell Transplantation Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, No. 32 Western Section 2, 1st Ring Rd., Chengdu, 610072, Sichuan, China
| | - Xiaolun Huang
- School of Medicine, University of Electronic Science and Technology of China, No. 4 Section 2, North Jianshe Road, Chengdu, 610054, Sichuan, China
- Department of Hepatobiliary Surgery and Cell Transplantation Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, No. 32 Western Section 2, 1st Ring Rd., Chengdu, 610072, Sichuan, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, No. 17 People's South Road, Chengdu, 610041, Sichuan, China.
| |
Collapse
|
|
23
|
Pu X, Deng D, Chu C, Zhou T, Liu J. High-dimensional hepatopath data analysis by machine learning for predicting HBV-related fibrosis. Sci Rep 2021; 11:5081. [PMID: 33658585 PMCID: PMC7930086 DOI: 10.1038/s41598-021-84556-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 02/16/2021] [Indexed: 11/09/2022] Open
Abstract
Chronic HBV infection, the main cause of liver cirrhosis and hepatocellular carcinoma, has become a global health concern. Machine learning algorithms are particularly adept at analyzing medical phenomenon by capturing complex and nonlinear relationships in clinical data. Our study proposed a predictive model on the basis of 55 routine laboratory and clinical parameters by machine learning algorithms as a novel non-invasive method for liver fibrosis diagnosis. The model was further evaluated on the accuracy and rationality and proved to be highly accurate and efficient for the prediction of HBV-related fibrosis. In conclusion, we suggested a potential combination of high-dimensional clinical data and machine learning predictive algorithms for the liver fibrosis diagnosis.
Collapse
Affiliation(s)
- Xiangke Pu
- Institute of Hepatology, The Third People's Hospital of Changzhou, Changzhou, 213001, China
| | - Danni Deng
- Department of Neurosurgery, The First People's Hospital of Changzhou, Changzhou, 213001, China
| | - Chaoyi Chu
- Library, Jiangsu University of Technology, Changzhou, 213001, China
| | - Tianle Zhou
- School of Computer Science and Engineering, Jiangsu University of Technology, Changzhou, 213001, China.
| | - Jianhong Liu
- Institute of Hepatology, The Third People's Hospital of Changzhou, Changzhou, 213001, China.
| |
Collapse
|
|
24
|
The Diagnosis Value of a Novel Model with 5 Circulating miRNAs for Liver Fibrosis in Patients with Chronic Hepatitis B. Mediators Inflamm 2021; 2021:6636947. [PMID: 33727891 PMCID: PMC7939739 DOI: 10.1155/2021/6636947] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 01/14/2021] [Accepted: 01/19/2021] [Indexed: 12/29/2022] Open
Abstract
Methods Differential expression of five selected miRNAs (hsa-mir-1225-3p, hsa-mir-1238, hsa-miR-3162-3P, hsa-miR-4721, and hsa-miR-H7) was verified by qRT-PCR in the plasma of 83 patients and 20 healthy controls. The relative expression of these miRNAs was analyzed in different groups to screen target miRNA. A logistic regression analysis was performed to assess factors associated with fibrosis progression. The receiver operating characteristic (ROC) curve and discriminant analyses validated the ability of these predicted variables to discriminate the nonsignificant liver fibrosis group from the significant liver fibrosis group. Furthermore, the established models were compared with other prediction models to evaluate the diagnostic efficiency. Results These five tested miRNAs all had signature correlations with hepatic fibrotic level (p < 0.05), and the upregulation trends were consistent with miRNA microarray analysis previously. The multivariate logistic regression analysis identified that a model of five miRNAs (miR-5) had a high diagnostic accuracy in discrimination of different stages of liver fibrosis. The ROC showed that the miR-5 has excellent value in diagnosis of fibrosis, even better than the Forns score, FIB-4, S index, and APRI. GO functions of different miRNAs mainly involved in various biological processes were markedly involved in HBV and revealed signaling pathways dysregulated in liver fibrosis of CHB patients. Conclusions It was validated that the combination of these five miRNAs was a new set of promising molecular diagnostic markers for liver fibrosis. The diagnosis model (miR-5) can distinguish significant and nonsignificant liver fibrosis with high sensitivity and specificity.
Collapse
|
|
25
|
He D, Zhang C, Qiu W, Xie Q. Diagnosis of liver fibrosis in patients with hepatitis B-related liver disease using ultrasound with wave-number domain attenuation coefficient. TURKISH JOURNAL OF GASTROENTEROLOGY 2021; 31:923-929. [PMID: 33626006 DOI: 10.5152/tjg.2020.20139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND/AIMS The importance of identifying the stage of liver fibrosis has motivated the development of non-invasive methods. This study aimed to evaluate the applicability of ultrasound analysis involving the wave-number domain attenuation coefficient (W-Ac) in the non-invasive quantitative differentiation of liver fibrosis. MATERIALS AND METHODS This was a prospective study of inpatients with hepatitis B-related liver disease treated between October 2016 and January 2018. In ultrasound, the echo from the near-field liver tissue was selected as the reference signal. The W-Ac of liver tissues was based on the fast Fourier transform of the acquired post-beamforming radio frequency signals. These values were compared with fibrosis from biopsy METAVIR score results. A receiver operating characteristic (ROC) curve tested the W-Ac method. RESULTS A total of 46 patients were enrolled, including 27 males and 19 females. Fibrosis was stage F0 in 12 patients, F1 in 13 patients, F2 in 10 patients, F3 in 7 patients, and F4 in 4 patients. W-Ac increased with the progression of liver fibrosis up to stage F3. There were differences between F0 and F4 stages (p<0.001) and between any 2 stages of fibrosis (p<0.05), except for stages F3 and F4. There was a significant correlation between W-Ac and METAVIR score (r=0.795, p<0.001). W-Ac differed between non-fibrosis (F0) and fibrosis (F1-F4) groups (p<0.001) and in the normal (F0), early fibrosis (F1-2), and late fibrosis groups (F3-4) (p<0.001). ROC area under the curve was 0.890, and at a cut-off of 0.12153, sensitivity was 0.706 and specificity was 0.830. CONCLUSIONS W-Ac allowed assessment of liver fibrosis in clinical practice.
Collapse
Affiliation(s)
- Danqing He
- Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China
| | - Chaoxue Zhang
- Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China
| | - Wenqian Qiu
- Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China
| | - Qinxiu Xie
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China
| |
Collapse
|
|
26
|
Rong X, Ailing F, Xiaodong L, Jie H, Min L. Monitoring hepatitis B by using point-of-care testing: biomarkers, current technologies, and perspectives. Expert Rev Mol Diagn 2021; 21:195-211. [PMID: 33467927 DOI: 10.1080/14737159.2021.1876565] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Introduction: Liver diseases caused by hepatitis B virus (HBV) are pandemic infectious diseases that seriously endanger human health, conventional diagnosis methods can not meet the requirements in resource-limited areas. The point of acre detection methods can easily resolve those problems. Herein, we review the most recent advances in POC-based hepatitis B detection methods and present some recommendations for future development. It aims to provide ideas for future research.Areas covered: Epidemiological data on Hepatitis B, conventional diagnostic methods for hepatitis B detection, some latest point of care detection methods for hepatitis B detection and list out the recommendations for future development.Expert opinion: This manuscript summarized traditional biomarkers of different hepatitis B stages and recent-developed POCT platforms (including microfluidic platforms and lateral-flow strips) and discuss the challenges associated with their use. Some emerging biomarkers that can be used in hepatitis B diagnosis are also listed. This manuscript has certain guiding significance to the development of hepatitis B detection.
Collapse
Affiliation(s)
- Xu Rong
- Institute of Physics & Optoelectronics Technology, Baoji University of Arts and Sciences, Baoji, China
| | - Feng Ailing
- Institute of Physics & Optoelectronics Technology, Baoji University of Arts and Sciences, Baoji, China
| | - Li Xiaodong
- Institute of Physics & Optoelectronics Technology, Baoji University of Arts and Sciences, Baoji, China
| | - Hu Jie
- Suzhou DiYinAn Biotech Co., Ltd. & Suzhou Innovation Center for Life Science and Technology, Suzhou, China
| | - Lin Min
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| |
Collapse
|
|
27
|
Mohr R, Özdirik B, Lambrecht J, Demir M, Eschrich J, Geisler L, Hellberg T, Loosen SH, Luedde T, Tacke F, Hammerich L, Roderburg C. From Liver Cirrhosis to Cancer: The Role of Micro-RNAs in Hepatocarcinogenesis. Int J Mol Sci 2021; 22:1492. [PMID: 33540837 PMCID: PMC7867354 DOI: 10.3390/ijms22031492] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 01/23/2021] [Accepted: 01/28/2021] [Indexed: 12/19/2022] Open
Abstract
In almost all cases, hepatocellular carcinoma (HCC) develops as the endpoint of a sequence that starts with chronic liver injury, progresses to liver cirrhosis, and finally, over years and decades, results in liver cancer. Recently, the role of non-coding RNA such as microRNA (miRNA) has been demonstrated in the context of chronic liver diseases and HCC. Moreover, data from a phase II trial suggested a potential role of microRNAs as therapeutics in hepatitis-C-virus infection, representing a significant risk factor for development of liver cirrhosis and HCC. Despite progress in the clinical management of chronic liver diseases, pharmacological treatment options for patients with liver cirrhosis and/or advanced HCC are still limited. With their potential to regulate whole networks of genes, miRNA might be used as novel therapeutics in these patients but could also serve as biomarkers for improved patient stratification. In this review, we discuss available data on the role of miRNA in the transition from liver cirrhosis to HCC. We highlight opportunities for clinical translation and discuss open issues applicable to future developments.
Collapse
Affiliation(s)
- Raphael Mohr
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (B.Ö.); (J.L.); (M.D.); (J.E.); (L.G.); (T.H.); (F.T.); (L.H.); (C.R.)
| | - Burcin Özdirik
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (B.Ö.); (J.L.); (M.D.); (J.E.); (L.G.); (T.H.); (F.T.); (L.H.); (C.R.)
| | - Joeri Lambrecht
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (B.Ö.); (J.L.); (M.D.); (J.E.); (L.G.); (T.H.); (F.T.); (L.H.); (C.R.)
| | - Münevver Demir
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (B.Ö.); (J.L.); (M.D.); (J.E.); (L.G.); (T.H.); (F.T.); (L.H.); (C.R.)
| | - Johannes Eschrich
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (B.Ö.); (J.L.); (M.D.); (J.E.); (L.G.); (T.H.); (F.T.); (L.H.); (C.R.)
| | - Lukas Geisler
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (B.Ö.); (J.L.); (M.D.); (J.E.); (L.G.); (T.H.); (F.T.); (L.H.); (C.R.)
| | - Teresa Hellberg
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (B.Ö.); (J.L.); (M.D.); (J.E.); (L.G.); (T.H.); (F.T.); (L.H.); (C.R.)
| | - Sven H. Loosen
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty of Heinrich Heine University Düsseldorf, University Hospital Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany; (S.H.L.); (T.L.)
| | - Tom Luedde
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty of Heinrich Heine University Düsseldorf, University Hospital Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany; (S.H.L.); (T.L.)
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (B.Ö.); (J.L.); (M.D.); (J.E.); (L.G.); (T.H.); (F.T.); (L.H.); (C.R.)
| | - Linda Hammerich
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (B.Ö.); (J.L.); (M.D.); (J.E.); (L.G.); (T.H.); (F.T.); (L.H.); (C.R.)
| | - Christoph Roderburg
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (B.Ö.); (J.L.); (M.D.); (J.E.); (L.G.); (T.H.); (F.T.); (L.H.); (C.R.)
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty of Heinrich Heine University Düsseldorf, University Hospital Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany; (S.H.L.); (T.L.)
| |
Collapse
|
|
28
|
Loureiro D, Tout I, Narguet S, Benazzouz SM, Mansouri A, Asselah T. miRNAs as Potential Biomarkers for Viral Hepatitis B and C. Viruses 2020; 12:E1440. [PMID: 33327640 PMCID: PMC7765125 DOI: 10.3390/v12121440] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 12/07/2020] [Accepted: 12/10/2020] [Indexed: 02/06/2023] Open
Abstract
Around 257 million people are living with hepatitis B virus (HBV) chronic infection and 71 million with hepatitis C virus (HCV) chronic infection. Both HBV and HCV infections can lead to liver complications such as cirrhosis and hepatocellular carcinoma (HCC). To take care of these chronically infected patients, one strategy is to diagnose the early stage of fibrosis in order to treat them as soon as possible to decrease the risk of HCC development. microRNAs (or miRNAs) are small non-coding RNAs which regulate many cellular processes in metazoans. Their expressions were frequently modulated by up- or down-regulation during fibrosis progression. In the serum of patients with HBV chronic infection (CHB), miR-122 and miR-185 expressions are increased, while miR-29, -143, -21 and miR-223 expressions are decreased during fibrosis progression. In the serum of patients with HCV chronic infection (CHC), miR-143 and miR-223 expressions are increased, while miR-122 expression is decreased during fibrosis progression. This review aims to summarize current knowledge of principal miRNAs modulation involved in fibrosis progression during chronic hepatitis B/C infections. Furthermore, we also discuss the potential use of miRNAs as non-invasive biomarkers to diagnose fibrosis with the intention of prioritizing patients with advanced fibrosis for treatment and surveillance.
Collapse
Affiliation(s)
| | | | | | | | | | - Tarik Asselah
- Department of Hepatology, Université de Paris, CRI, INSERM UMR 1149, AP-HP Hôpital Beaujon, 92110 Clichy, France; (D.L.); (I.T.); (S.N.); (S.M.B.); (A.M.)
| |
Collapse
|
|
29
|
The miR-21 potential of serving as a biomarker for liver diseases in clinical practice. Biochem Soc Trans 2020; 48:2295-2305. [PMID: 33119045 DOI: 10.1042/bst20200653] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Revised: 09/18/2020] [Accepted: 10/05/2020] [Indexed: 12/11/2022]
Abstract
The role of miR-21 in the pathogenesis of various liver diseases, together with the possibility of detecting microRNA in the circulation, makes miR-21 a potential biomarker for noninvasive detection. In this review, we summarize the potential utility of extracellular miR-21 in the clinical management of hepatic disease patients and compared it with the current clinical practice. MiR-21 shows screening and prognostic value for liver cancer. In liver cirrhosis, miR-21 may serve as a biomarker for the differentiating diagnosis and prognosis. MiR-21 is also a potential biomarker for the severity of hepatitis. We elucidate the disease condition under which miR-21 testing can reach the expected performance. Though miR-21 is a key regulator of liver diseases, microRNAs coordinate with each other in the complex regulatory network. As a result, the performance of miR-21 is better when combined with other microRNAs or classical biomarkers under certain clinical circumstances.
Collapse
|
|
30
|
Orr C, Myers R, Li B, Jiang Z, Flaherty J, Gaggar A, Meissner EG. Longitudinal analysis of serum microRNAs as predictors of cirrhosis regression during treatment of hepatitis B virus infection. Liver Int 2020; 40:1693-1700. [PMID: 32301252 PMCID: PMC7681260 DOI: 10.1111/liv.14474] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Revised: 01/27/2020] [Accepted: 04/08/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Most patients with cirrhosis induced by chronic HBV infection experience fibrosis regression after long-term antiviral treatment, while some remain cirrhotic. Fibrosis regression is associated with lower odds of developing hepatic decompensation and hepatocellular carcinoma, but mechanisms impacting differential fibrosis regression between individuals are unclear. We asked whether soluble molecules, including serum microRNAs, could serve as biomarkers of fibrosis regression. METHODS We analysed cryopreserved sera from clinical trials in which cirrhotic HBV-infected patients (baseline Ishak fibrosis score of 5-6) received 240 weeks of nucleotide analogue treatment. Liver biopsies at week 240 in these trials showed 71/96 patients (74%) had fibrosis regression (Ishak ≤ 4) while 25/96 (26%) remained cirrhotic (Ishak 5-6). We quantified inflammatory markers (CXCL10, soluble CD163) and miRNAs (n = 179) from serum at baseline, week 48 and week 240 of treatment in a sub-cohort of patients with (n = 14) or without (n = 14) fibrosis regression. RESULTS CXCL10, sCD163 and miRNAs previously associated with HBV replication and inflammation decreased during treatment but did not differ based on fibrosis regression. Two miRNAs (miR-421 and miR-454-3p) had lower baseline expression in patients with subsequent fibrosis regression. In all, 27 miRNAs differed at week 240 and had higher expression in patients with fibrosis regression (eg miR-199a-3p, miR-423-3p, miR-142-3p, miR-let-7d-5p). Several miRNAs (miR-141-3p, let-7d-5p) that correlated with regression have previously been implicated in the pathophysiology of non-alcoholic steatohepatitis. CONCLUSIONS In cirrhotic patients with chronic HBV infection treated with antiviral therapy, serum miRNAs have differential expression based on fibrosis regression, suggesting potential utility as biomarkers.
Collapse
Affiliation(s)
- Cody Orr
- Division of Infectious Diseases, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC
| | | | - Biao Li
- Gilead Sciences, Foster City, CA
| | | | | | | | - Eric G. Meissner
- Division of Infectious Diseases, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC
| |
Collapse
|
|
31
|
Iacob DG, Rosca A, Ruta SM. Circulating microRNAs as non-invasive biomarkers for hepatitis B virus liver fibrosis. World J Gastroenterol 2020; 26:1113-1127. [PMID: 32231417 PMCID: PMC7093315 DOI: 10.3748/wjg.v26.i11.1113] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 03/04/2020] [Accepted: 03/09/2020] [Indexed: 02/06/2023] Open
Abstract
Viruses can alter the expression of host microRNAs (MiRNA s) and modulate the immune response during a persistent infection. The dysregulation of host MiRNA s by hepatitis B virus (HBV) contributes to the proinflammatory and profibrotic changes within the liver. Multiple studies have documented the differential regulation of intracellular and circulating MiRNA s during different stages of HBV infection. Circulating MiRNA s found in plasma and/or extracellular vesicles can integrate data on viral-host interactions and on the associated liver injury. Hence, the detection of circulating MiRNA s in chronic HBV hepatitis could offer a promising alternative to liver biopsy, as their expression is associated with HBV replication, the progression of liver fibrosis, and the outcome of antiviral treatment. The current review explores the available data on miRNA involvement in HBV pathogenesis with an emphasis on their potential use as biomarkers for liver fibrosis.
Collapse
Affiliation(s)
- Diana Gabriela Iacob
- Infectious Diseases Department, "Carol Davila" University of Medicine and Pharmacy, Bucharest 050474, Romania
- Bucharest Emergency University Hospital, Bucharest 050098, Romania
| | - Adelina Rosca
- Virology Department, Carol Davila University of Medicine and Pharmacy, Bucharest 050474, Romania
- Viral Emerging Diseases Department, Ștefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Simona Maria Ruta
- Virology Department, Carol Davila University of Medicine and Pharmacy, Bucharest 050474, Romania
- Viral Emerging Diseases Department, Ștefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| |
Collapse
|
|
32
|
Lu QQ, Chen M, Wang XL, Cao SQ. Meta-analysis of diagnostic value of circulating microRNAs in hepatitis B-related fibrosis. Shijie Huaren Xiaohua Zazhi 2019; 27:1365-1374. [DOI: 10.11569/wcjd.v27.i22.1365] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is a major cause of viral hepatitis, liver fibrosis, and liver cirrhosis worldwide. Liver fibrosis is initially reversible, but without early diagnosis and timely treatment, it can progress to end-stage liver diseases such as cirrhosis, liver failure, and even liver cancer. Therefore, the accurate diagnosis of hepatic fibrosis plays a decisive role in the management and treatment of chronic hepatitis B (CHB) patients. However, accurate diagnostic markers are still lacking.
AIM To systemically evaluate the diagnostic accuracy of circulating microRNAs (miRNAs) in hepatitis B-related fibrosis.
METHODS The PubMed, Cochrane Library, and Embase databases were searched for all eligible studies using the following search terms: ("serum" or "plasma" or "circulating" or "blood") and ("microRNA" or "miRNA" or "miR*") and ("hepatitis B" or "CHB" or "viral hepatitis*" or "chronic hepatitis") and ("liver fibrosis" or "liver cirrhosis" or "hepatic fibrosis*"). The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristics curve (AUROC) were pooled to assess the accuracy of circulating miRNAs for the diagnosis of early fibrosis, advanced fibrosis, and cirrhosis.
RESULTS A total of 15 studies with 1623 CHB patients were enrolled in this meta-analysis. The pooled sensitivity, specificity, and AUROC of using circulating miRNAs for the diagnosis of hepatitis B-related early fibrosis were 0.76 (95%CI: 0.69-0.82), 0.64 (95%CI: 0.47-0.78), and 0.78 (95%CI: 0.74-0.81), respectively. The pooled sensitivity, specificity, and AUROC of using circulating miRNAs for the diagnosis of hepatitis B-related advanced fibrosis were 0.79 (95%CI: 0.72-0.85), 0.81(95%CI: 0.63-0.91), and 0.82 (95%CI: 0.79-0.85), respectively. Only two studies assessed the diagnostic accuracy of circulating miRNAs for predicting cirrhosis, and the results suggested that circulating miRNAs provided a high diagnostic accuracy for CHB-related cirrhosis (AUROC = 0.882; accuracy, 93.7%).
CONCLUSION Circulating miRNAs show pretty good diagnostic accuracy for hepatitis B-related fibrosis, especially for advanced fibrosis and cirrhosis, and can be used as potential circulating biomarkers for the diagnosis of liver fibrosis in CHB patients.
Collapse
Affiliation(s)
- Qing-Qing Lu
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430061, Hubei Province, China
| | - Min Chen
- Department of Emergency Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430061, Hubei Province, China
| | - Xiao-Lin Wang
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430061, Hubei Province, China
| | - Shi-Qiong Cao
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430061, Hubei Province, China
| |
Collapse
|
|
33
|
The Regulatory Role of MicroRNA in Hepatitis-B Virus-Associated Hepatocellular Carcinoma (HBV-HCC) Pathogenesis. Cells 2019; 8:cells8121504. [PMID: 31771261 PMCID: PMC6953055 DOI: 10.3390/cells8121504] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 11/11/2019] [Accepted: 11/12/2019] [Indexed: 02/06/2023] Open
Abstract
The incidence and mortality of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC) is an intractable public health problem in developing countries that is compounded by limited early detection and therapeutic options. Despite the early promise of utilizing the regulatory role of miRNA in liver cancer, this field remains largely in the work-in-progress phase. This exploratory review paper adopts a broad focus in order to collate evidence of the regulatory role of miRNA in each stage of the HBV-HCC continuum. This includes the regulatory role of miRNA in early HBV infection, chronic inflammation, fibrosis/cirrhosis, and the onset of HCC. The paper specifically investigates HBV dysregulated miRNA that influence the expression of the host/HBV genome in HBV-HCC pathogenesis and fully acknowledges that this does not cover the full spectrum of dysregulated miRNA. The sheer number of dysregulated miRNA in each phase support a hypothesis that future therapeutic interventions will need to consider incorporating multiple miRNA panels.
Collapse
|
|
34
|
Lambrecht J, Verhulst S, Reynaert H, van Grunsven LA. The miRFIB-Score: A Serological miRNA-Based Scoring Algorithm for the Diagnosis of Significant Liver Fibrosis. Cells 2019; 8:cells8091003. [PMID: 31470644 PMCID: PMC6770498 DOI: 10.3390/cells8091003] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 08/22/2019] [Accepted: 08/27/2019] [Indexed: 12/14/2022] Open
Abstract
Background: The current diagnosis of early-stage liver fibrosis often relies on a serological or imaging-based evaluation of the stage of fibrosis, sometimes followed by an invasive liver biopsy procedure. Novel non-invasive experimental diagnostic tools are often based on markers of hepatocyte damage, or changes in liver stiffness and architecture, which are late-stage characteristics of fibrosis progression, making them unsuitable for the diagnosis of early-stage liver fibrosis. miRNAs control hepatic stellate cell (HSC) activation and are proposed as relevant diagnostic markers. Methods: We investigated the possibility of circulating miRNAs, which we found to be dysregulated upon HSC activation, to mark the presence of significant liver fibrosis (F ≥ 2) in patients with chronic alcohol abuse, chronic viral infection (HBV/HCV), and non-alcoholic fatty liver disease (NAFLD). Results: miRNA-profiling identified miRNA-451a, miRNA-142-5p, Let-7f-5p, and miRNA-378a-3p to be significantly dysregulated upon in vitro HSC activation, and to be highly enriched in their extracellular vesicles, suggesting their potential use as biomarkers. Analysis of the plasma of patients with significant liver fibrosis (F ≥ 2) and no or mild fibrosis (F = 0–1), using miRNA-122-5p and miRNA-29a-3p as positive control, found miRNA-451a, miRNA-142-5p, and Let-7f-5p, but not miRNA-378a-3p, able to distinguish between the two patient populations. Using logistic regression analysis, combining all five dysregulated circulating miRNAs, we created the miRFIB-score with a predictive value superior to the clinical scores Fibrosis-4 (Fib-4), aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and AST to platelet ratio index (APRI). The combination of the miRFIB-score with circulating PDGFRβ-levels further increased the predictive capacity for the diagnosis of significant liver fibrosis. Conclusions: The miRFIB- and miRFIBp-scores are accurate tools for the diagnosis of significant liver fibrosis in a heterogeneous patient population.
Collapse
Affiliation(s)
- Joeri Lambrecht
- Department of Basic (Bio-)Medical Sciences, Liver Cell Biology Research Group, Vrije Universiteit Brussel, 1050 Brussels, Belgium
| | - Stefaan Verhulst
- Department of Basic (Bio-)Medical Sciences, Liver Cell Biology Research Group, Vrije Universiteit Brussel, 1050 Brussels, Belgium
| | - Hendrik Reynaert
- Department of Basic (Bio-)Medical Sciences, Liver Cell Biology Research Group, Vrije Universiteit Brussel, 1050 Brussels, Belgium
- Department of Gastroenterology and Hepatology, University Hospital Brussels (UZ Brussel), B-1090 Brussels, Belgium
| | - Leo A van Grunsven
- Department of Basic (Bio-)Medical Sciences, Liver Cell Biology Research Group, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
| |
Collapse
|
|
35
|
Tao YC, Wang ML, Chen EQ. Reply to: "The crucial need of internal control validation in the normalization of circulating microRNAs". Dig Liver Dis 2019; 51:611-612. [PMID: 30824407 DOI: 10.1016/j.dld.2019.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 02/02/2019] [Accepted: 02/06/2019] [Indexed: 12/11/2022]
Affiliation(s)
- Ya-Chao Tao
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China; Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, PR China
| | - Meng-Lan Wang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China; Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, PR China
| | - En-Qiang Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China; Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, PR China.
| |
Collapse
|
|
36
|
Epigenetics of autoimmune liver diseases: current progress and future directions. JOURNAL OF BIO-X RESEARCH 2019. [DOI: 10.1097/jbr.0000000000000030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
|
|
37
|
Bian H, Zhou Y, Zhou D, Zhang Y, Shang D, Qi J. The latest progress on miR-374 and its functional implications in physiological and pathological processes. J Cell Mol Med 2019; 23:3063-3076. [PMID: 30772950 PMCID: PMC6484333 DOI: 10.1111/jcmm.14219] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 01/10/2019] [Accepted: 01/23/2019] [Indexed: 12/17/2022] Open
Abstract
Non‐coding RNAs (ncRNAs) have been emerging players in cell development, differentiation, proliferation and apoptosis. Based on their differences in length and structure, they are subdivided into several categories including long non‐coding RNAs (lncRNAs >200nt), stable non‐coding RNAs (60‐300nt), microRNAs (miRs or miRNAs, 18‐24nt), circular RNAs, piwi‐interacting RNAs (26‐31nt) and small interfering RNAs (about 21nt). Therein, miRNAs not only directly regulate gene expression through pairing of nucleotide bases between the miRNA sequence and a specific mRNA that leads to the translational repression or degradation of the target mRNA, but also indirectly affect the function of downstream genes through interactions with lncRNAs and circRNAs. The latest studies have highlighted their importance in physiological and pathological processes. MiR‐374 family member are located at the X‐chromosome inactivation center. In recent years, numerous researches have uncovered that miR‐374 family members play an indispensable regulatory role, such as in reproductive disorders, cell growth and differentiation, calcium handling in the kidney, various cancers and epilepsy. In this review, we mainly focus on the role of miR‐374 family members in multiple physiological and pathological processes. More specifically, we also summarize their promising potential as novel prognostic biomarkers and therapeutic targets from bench to bedside.
Collapse
Affiliation(s)
- Hongjun Bian
- Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Yi Zhou
- Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Dawei Zhou
- Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Yongsheng Zhang
- Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Deya Shang
- Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Jianni Qi
- Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| |
Collapse
|
|
38
|
Jiang S, Jiang W, Xu Y, Wang X, Mu Y, Liu P. Serum miR-21 and miR-26a Levels Negatively Correlate with Severity of Cirrhosis in Patients with Chronic Hepatitis B. Microrna 2019; 8:86-92. [PMID: 30147020 DOI: 10.2174/2211536607666180821162850] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 07/17/2018] [Accepted: 08/20/2018] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND OBJECTIVE Accurately evaluating the severity of liver cirrhosis is essential for clinical decision making and disease management. This study aimed to evaluate the value of circulating levels of microRNA (miR)-26a and miR-21 as novel noninvasive biomarkers in detecting severity of cirrhosis in patients with chronic hepatitis B. METHODS Thirty patients with clinically diagnosed chronic hepatitis B-related cirrhosis and 30 healthy individuals were selected. The serum levels of miR-26a and miR-21 were quantified by qRT-PCR. Receiver operating characteristic curve analysis was performed to evaluate the sensitivity and specificity of the miRNAs for detecting the severity of cirrhosis. RESULTS Serum miR-26a and miR-21 levels were found to be significantly downregulated in patients with severe cirrhosis scored at Child-Pugh class C in comparison to healthy controls (miR-26a p<0.01, and miR-21 p<0.001, respectively). The circulating miR-26a and miR-21 levels in patients were positively correlated with serum albumin concentration but negatively correlated with serum total bilirubin concentration and prothrombin time. Receiver operating characteristic curve analysis revealed that both serum miR-26a and miR-21 levels were associated with a high diagnostic accuracy for patients with cirrhosis scored at Child-Pugh class C (miR-26a Cut-off fold change at ≤0.4, Sensitivity: 84.62%, Specificity: 89.36%, P<0.0001; miR-21 Cut-off fold change at ≤0.6, Sensitivity: 84.62%, Specificity: 78.72%, P<0.0001). CONCLUSION Our results indicate that the circulating levels of miR-26a and miR-21 are closely related to the extent of liver decompensation, and the decreased levels are capable of discriminating patients with cirrhosis at Child-Pugh class C from the whole cirrhosis cases.
Collapse
Affiliation(s)
- Shili Jiang
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Wei Jiang
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ying Xu
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xiaoning Wang
- E-Institute of Shanghai Municipal Education Committee, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yongping Mu
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ping Liu
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- E-Institute of Shanghai Municipal Education Committee, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| |
Collapse
|
|
39
|
Sagnelli E, Potenza N, Onorato L, Sagnelli C, Coppola N, Russo A. Micro-RNAs in hepatitis B virus-related chronic liver diseases and hepatocellular carcinoma. World J Hepatol 2018; 10:558-570. [PMID: 30310534 PMCID: PMC6177563 DOI: 10.4254/wjh.v10.i9.558] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2018] [Revised: 04/24/2018] [Accepted: 05/30/2018] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that modulate gene expression at the post-transcriptional level by affecting both the stability and translation of complementary mRNAs. Several studies have shown that miRNAs are important regulators in the conflicting efforts between the virus (to manipulate the host for its successful propagation) and the host (to inhibit the virus), culminating in either the elimination of the virus or its persistence. An increasing number of studies report a role of miRNAs in hepatitis B virus (HBV) replication and pathogenesis. In fact, HBV is able to modulate different host miRNAs, particularly through the transcriptional transactivator HBx protein and, conversely, different cellular miRNAs can regulate HBV gene expression and replication by a direct binding to HBV transcripts or indirectly targeting host factors. The present review will discuss the role of miRNAs in the pathogenesis of HBV-related diseases and their role as a biomarker in the management of patients with HBV-related disease and as therapeutic targets.
Collapse
Affiliation(s)
- Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80135, Italy.
| | - Nicoletta Potenza
- DISTABIF, University of Campania "Luigi Vanvitelli", Naples 80100, Italy
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80135, Italy
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80135, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80135, Italy
| | - Aniello Russo
- DISTABIF, University of Campania "Luigi Vanvitelli", Naples 80100, Italy
| |
Collapse
|
|
40
|
Role of miR-223 in the pathophysiology of liver diseases. Exp Mol Med 2018; 50:1-12. [PMID: 30258086 PMCID: PMC6158210 DOI: 10.1038/s12276-018-0153-7] [Citation(s) in RCA: 85] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 05/17/2018] [Accepted: 06/12/2018] [Indexed: 02/08/2023] Open
Abstract
MiRNAs are small, noncoding RNAs, which can regulate gene expression posttranscriptionally, and they have emerged as key factors in disease biology by aiding in disease development and progression. MiR-223 is highly conserved during evolution and it was first described as a modulator of hematopoietic lineage differentiation. MiR-223 has an essential part in inflammation by targeting the nuclear factor-κB pathway and the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome. Recent studies have shown that miR-223 expression is deregulated in various types of liver diseases, including hepatitis virus infections, alcohol-induced liver injury, drug-induced liver injury, non-alcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma. As inflammatory and immune factors are involved in the occurrence and progress of liver diseases, deregulated miR-223 may participate in the pathogenesis of these conditions by influencing neutrophil infiltration, macrophage polarization, and inflammasome activation. This review first summarizes the present understanding of the biological functions of miR-223, including its gene location and transcription regulation, as well as its physiological role in hematopoietic differentiation. This review then focuses on the role of miR-223 in liver pathophysiology and its potential applications as a diagnostic biomarker and therapeutic target in liver diseases. A tiny RNA molecule involved with gene regulation may offer an appealing target for diagnosing and treating various liver diseases. MicroRNA-223 (miR-223) was first identified as controlling gene activity in a wide variety of immune cells. A review from researchers led by Yanning Liu at China’s Zhejiang University in Hangzhou details how abnormal miR-223 also contributes to liver damage in a variety of conditions, although questions still remain about how it functions in different liver disorders. The authors highlight studies linking miR-223 with the development of fibrosis and cirrhosis, and with the inflammatory response to injury from drugs, alcohol, or infection. This could make this microRNA a useful diagnostic biomarker. The authors also identify therapeutic opportunities to modulate this molecule, referring to several studies on the manipulation of miR-223 to treat hepatitis.
Collapse
|