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Zhang L, Cui TX, Li XZ, Liu C, Wang WQ. Diagnostic and prognostic role of LINC01767 in hepatocellular carcinoma. World J Hepatol 2024; 16:932-950. [PMID: 38948436 PMCID: PMC11212654 DOI: 10.4254/wjh.v16.i6.932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 04/08/2024] [Accepted: 04/28/2024] [Indexed: 06/20/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a primary contributor to cancer-related mortality on a global scale. However, the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs are emerging markers for HCC diagnosis, prognosis, and therapeutic target. No study of LINC01767 in HCC was published. AIM To conduct a multi-omics analysis to explore the roles of LINC01767 in HCC for the first time. METHODS DESeq2 Package was used to analyze different gene expressions. Receiver operating characteristic curves assessed the diagnostic performance. Kaplan-Meier univariate and Cox multivariate analyses were used to perform survival analysis. The least absolute shrinkage and selection operator (LASSO)-Cox was used to identify the prediction model. Subsequent to the validation of LINC01767 expression in HCC fresh frozen tissues through quantitative real time polymerase chain reaction, next generation sequencing was performed following LINC01767 over expression (GSE243371), and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes/Gene Set Enrichment Analysis/ingenuity pathway analysis was carried out. In vitro experiment in Huh7 cell was carried out. RESULTS LINC01767 was down-regulated in HCC with a log fold change = 1.575 and was positively correlated with the cancer stemness. LINC01767 was a good diagnostic marker with area under the curve (AUC) [0.801, 95% confidence interval (CI): 0.751-0.852, P = 0.0106] and an independent predictor for overall survival (OS) with hazard ratio = 1.899 (95%CI: 1.01-3.58, P = 0.048). LINC01767 nomogram model showed a satisfied performance. The top-ranked regulatory network analysis of LINC01767 showed the regulation of genes participating various pathways. LASSO regression identified the 9-genes model showing a more satisfied performance than 5-genes model to predict the OS with AUC > 0.75. LINC01767 was down-expressed obviously in tumor than para-tumor tissues in our cohort as well as in cancer cell line; the over expression of LINC01767 inhibit cell proliferation and clone formation of Huh7 in vitro. CONCLUSION LINC01767 was an important tumor suppressor gene in HCC with good diagnostic and prognostic performance.
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Affiliation(s)
- Li Zhang
- Department of Thyroid and Breast Surgery, The Affiliated People Hospital of Second Medical University, Weifang 266010, Shandong Province, China
| | - Tong-Xing Cui
- Department of General Surgery, Qingdao Municipal Hospital Group, Qingdao 266237, Shandong Province, China
| | - Xiang-Zhi Li
- School of Life Sciences, Shandong University (Qingdao), Qingdao 26637, Shandong Province, China
| | - Chong Liu
- School of Medicine, Tsinghua University, Beijing 100084, China
| | - Wen-Qin Wang
- School of Life Sciences, Shandong University (Qingdao), Qingdao 26637, Shandong Province, China.
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Lv H, Qian D, Xu S, Fan G, Qian Q, Cha D, Qian X, Zhou G, Lu B. Modulation of long noncoding RNAs by polyphenols as a novel potential therapeutic approach in lung cancer: A comprehensive review. Phytother Res 2024; 38:3240-3267. [PMID: 38739454 DOI: 10.1002/ptr.8202] [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: 11/13/2023] [Revised: 03/10/2024] [Accepted: 03/19/2024] [Indexed: 05/16/2024]
Abstract
Lung cancer stands as a formidable global health challenge, necessitating innovative therapeutic strategies. Polyphenols, bioactive compounds synthesized by plants, have garnered attention for their diverse health benefits, particularly in combating various cancers, including lung cancer. The advent of whole-genome and transcriptome sequencing technologies has illuminated the pivotal roles of long noncoding RNAs (lncRNAs), operating at epigenetic, transcriptional, and posttranscriptional levels, in cancer progression. This review comprehensively explores the impact of polyphenols on both oncogenic and tumor-suppressive lncRNAs in lung cancer, elucidating on their intricate regulatory mechanisms. The comprehensive examination extends to the potential synergies when combining polyphenols with conventional treatments like chemotherapy, radiation, and immunotherapy. Recognizing the heterogeneity of lung cancer subtypes, the review emphasizes the need for the integration of nanotechnology for optimized polyphenol delivery and personalized therapeutic approaches. In conclusion, we collect the latest research, offering a holistic overview of the evolving landscape of polyphenol-mediated modulation of lncRNAs in lung cancer therapy. The integration of polyphenols and lncRNAs into multidimensional treatment strategies holds promise for enhancing therapeutic efficacy and navigating the challenges associated with lung cancer treatment.
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Affiliation(s)
- Hong Lv
- Department of Pulmonary and Critical Care Medicine, Taicang TCM Hospital, Taicang, China
| | - Dawei Qian
- Department of Thoracic Surgery, Tongling Yi'an District People's Hospital, Tongling, China
| | - Shuhua Xu
- Department of Cardiothoracic Surgery, Dongtai Hospital of Traditional Chinese Medicine, Dongtai, China
| | - Guiqin Fan
- Department of Pulmonary and Critical Care Medicine, Taicang TCM Hospital, Taicang, China
| | - Qiuhong Qian
- Department of Pulmonary and Critical Care Medicine, Taicang TCM Hospital, Taicang, China
| | - Dongsheng Cha
- Department of Thoracic Surgery, Tongling Yi'an District People's Hospital, Tongling, China
| | - Xingjia Qian
- Department of Pulmonary and Critical Care Medicine, Taicang TCM Hospital, Taicang, China
| | - Guoping Zhou
- Department of Cardiothoracic Surgery, Dongtai Hospital of Traditional Chinese Medicine, Dongtai, China
| | - Bing Lu
- Department of Pulmonary and Critical Care Medicine, Taicang TCM Hospital, Taicang, China
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3
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Liang W, Zhao Y, Meng Q, Jiang W, Deng S, Xue J. The role of long non-coding RNA in hepatocellular carcinoma. Aging (Albany NY) 2024; 16:4052-4073. [PMID: 38334963 PMCID: PMC10929815 DOI: 10.18632/aging.205523] [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: 05/19/2023] [Accepted: 12/12/2023] [Indexed: 02/10/2024]
Abstract
Hepatocellular carcinoma (HCC) is a prevalent liver malignancy with complex etiology and generally poor prognosis. Recently, long non-coding RNAs (lncRNAs), non-protein-coding RNA molecules exceeding 200 nucleotides, have emerged as pivotal players in HCC, influencing its initiation, progression, invasion, and metastasis. These lncRNAs modulate gene expression at epigenetic, transcriptional, and post-transcriptional levels, actively participating in the pathological and physiological processes of HCC. Understanding the intricate relationship between lncRNAs and HCC is important for improving prognosis and reducing mortality. This review summarizes advancements in elucidating the role of lncRNAs in HCC pathogenesis.
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Affiliation(s)
- Weizheng Liang
- Central Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
- Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
- Tumor Research Institute, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
| | - Yan Zhao
- Department of Mathematics and Computer Science, Free University Berlin, Berlin 14195, Germany
| | - Qingxue Meng
- Technology Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
| | - Wenjie Jiang
- Department of Artificial Intelligence and Data Science, Hebei University of Technology, Tianjin 300401, China
| | - Shoulong Deng
- National Health Commission of China (NHC) Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100021, China
| | - Jun Xue
- Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
- Tumor Research Institute, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China
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4
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Lumkul L, Jantaree P, Jaisamak K, Wongkummool W, Lapisatepun W, Orrapin S, Udomruk S, Lo Piccolo L, Chaiyawat P. Combinatorial Gene Expression Profiling of Serum HULC, HOTAIR, and UCA1 lncRNAs to Differentiate Hepatocellular Carcinoma from Liver Diseases: A Systematic Review and Meta-Analysis. Int J Mol Sci 2024; 25:1258. [PMID: 38279264 PMCID: PMC10816616 DOI: 10.3390/ijms25021258] [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: 12/27/2023] [Revised: 01/11/2024] [Accepted: 01/16/2024] [Indexed: 01/28/2024] Open
Abstract
Hepatocellular carcinoma (HCC) presents a significant global health challenge due to limited early detection methods, primarily relying on conventional approaches like imaging and alpha-fetoprotein (AFP). Although non-coding RNAs (ncRNAs) show promise as potential biomarkers in HCC, their true utility remains uncertain. We conducted a comprehensive review of 76 articles, analyzing 88 circulating lncRNAs in 6426 HCC patients. However, the lack of a standardized workflow protocol has hampered holistic comparisons across the literature. Consequently, we herein confined our meta-analysis to only a subset of these lncRNAs. The combined analysis of serum highly upregulated in liver cancer (HULC) gene expression with homeobox transcript antisense intergenic RNA (HOTAIR) and urothelial carcinoma-associated 1 (UCA1) demonstrated markedly enhanced sensitivity and specificity in diagnostic capability compared to traditional biomarkers or other ncRNAs. These findings could have substantial implications for the early diagnosis and tailored treatment of HCC.
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MESH Headings
- Humans
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/pathology
- Liver Neoplasms/diagnosis
- Liver Neoplasms/genetics
- Liver Neoplasms/pathology
- RNA, Long Noncoding/metabolism
- Genes, Homeobox
- RNA, Antisense
- Carcinoma, Transitional Cell/genetics
- Gene Expression Regulation, Neoplastic
- Urinary Bladder Neoplasms/genetics
- RNA, Untranslated
- Biomarkers
- Gene Expression Profiling
- Biomarkers, Tumor/genetics
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Affiliation(s)
- Lalita Lumkul
- Center of Multidisciplinary Technology for Advanced Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (L.L.); (P.J.); (K.J.); (W.W.); (S.O.); (S.U.)
- Center for Clinical Epidemiology and Clinical Statistics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Phatcharida Jantaree
- Center of Multidisciplinary Technology for Advanced Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (L.L.); (P.J.); (K.J.); (W.W.); (S.O.); (S.U.)
| | - Kritsada Jaisamak
- Center of Multidisciplinary Technology for Advanced Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (L.L.); (P.J.); (K.J.); (W.W.); (S.O.); (S.U.)
| | - Wasinee Wongkummool
- Center of Multidisciplinary Technology for Advanced Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (L.L.); (P.J.); (K.J.); (W.W.); (S.O.); (S.U.)
| | - Worakitti Lapisatepun
- Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand;
| | - Santhasiri Orrapin
- Center of Multidisciplinary Technology for Advanced Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (L.L.); (P.J.); (K.J.); (W.W.); (S.O.); (S.U.)
| | - Sasimol Udomruk
- Center of Multidisciplinary Technology for Advanced Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (L.L.); (P.J.); (K.J.); (W.W.); (S.O.); (S.U.)
| | - Luca Lo Piccolo
- Center of Multidisciplinary Technology for Advanced Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (L.L.); (P.J.); (K.J.); (W.W.); (S.O.); (S.U.)
| | - Parunya Chaiyawat
- Center of Multidisciplinary Technology for Advanced Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (L.L.); (P.J.); (K.J.); (W.W.); (S.O.); (S.U.)
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Abdelsattar S, Fahim SA, Kamel HFM, Al-Amodi H, Kasemy ZA, Khalil FO, Abdallah MS, Bedair HM, Gadallah ANAA, Sabry A, Sakr MA, Selim M, Gayed EMAE. The Potential Role of Circulating Long Miscellaneous RNAs in the Diagnosis and Prognosis of Hepatitis C Related Hepatocellular Carcinoma. Noncoding RNA 2023; 9:62. [PMID: 37888208 PMCID: PMC10609931 DOI: 10.3390/ncrna9050062] [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: 08/27/2023] [Revised: 10/04/2023] [Accepted: 10/08/2023] [Indexed: 10/28/2023] Open
Abstract
Ribonucleic acids (RNAs) are important regulators of gene expression and crucial for the progression of hepatocellular carcinoma (HCC). This study was designed to determine the diagnostic and prognostic utility of the circulating long miscellaneous RNAs; LINC01419, AK021443, and AF070632 in HCV-related HCC patients. Real-time PCR was used to measure their relative expression levels in the plasma of 194 HCV patients, 120 HCV-related HCC patients and 120 healthy controls. LINC01419 and AK021443 expression levels had significantly increasing linear trend estimates while AF070632 was dramatically downregulated in HCC compared to HCV. Interestingly, LINC01419 and AK021443 served as more significant diagnostic biomarkers for HCC than AF070632 and AFP. Multivariate analysis with cox regression revealed that the high expression of AK021443 [HR = 10.06, CI95%: 3.36-30.07], the high expression of LINC01419 [HR 4.13, CI95%: 1.32-12.86], and the low expression of AF070632 [HR = 2.70, CI95%: 1.07-6.81] were significant potential prognostic factors for HCC. Besides, the Kaplan-Meier analysis showed that HCC patients with high LIN01419 and AK021443 and low AF070632 expression levels had shorter OS. The circulating LINC01419 and AK021443 can be used as noninvasive potential biomarkers for diagnosis and prognosis of HCV-related HCC patients than AF070632 providing new targets for limiting the progression of the disease.
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Affiliation(s)
- Shimaa Abdelsattar
- Clinical Biochemistry and Molecular Diagnostics Department, National Liver Institute, Menoufia University, Shebin El-Kom 32511, Egypt
| | - Sally A. Fahim
- Biochemistry Department, School of Pharmacy, Newgiza University (NGU), Cairo 94114, Egypt;
| | - Hala F. M. Kamel
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt;
- Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia;
| | - Hiba Al-Amodi
- Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia;
| | - Zeinab A. Kasemy
- Department of Public Health and Community Medicine, Faculty of Medicine, Menoufia University, Shebin El-Kom 32511, Egypt;
| | - Fatma O. Khalil
- Clinical Microbiology and Immunology Department, National Liver Institute, Menoufia University, Shebin El-Kom 32511, Egypt;
| | - Mahmoud S. Abdallah
- Clinical Pharmacy Department, Faculty of Pharmacy, University of Sadat City (USC), Sadat City 32897, Egypt;
| | - Hanan M. Bedair
- Clinical Pathology Department, National Liver Institute, Menoufia University, Shebin El-Kom 32511, Egypt;
| | | | - Aliaa Sabry
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom 32511, Egypt;
| | - Mohamed A. Sakr
- Medical Microbiology and Immunology Department, Faculty of Medicine, Suez University, Suez 43512, Egypt;
| | - Mahmoud Selim
- Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta 31111, Egypt;
| | - Eman M. Abd El Gayed
- Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Shebin El-Kom 32511, Egypt;
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Behnia M, Bradfute SB. The Host Non-Coding RNA Response to Alphavirus Infection. Viruses 2023; 15:v15020562. [PMID: 36851776 PMCID: PMC9967650 DOI: 10.3390/v15020562] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/10/2023] [Accepted: 02/15/2023] [Indexed: 02/22/2023] Open
Abstract
Alphaviruses are important human and animal pathogens that can cause a range of debilitating symptoms and are found worldwide. These include arthralgic diseases caused by Old-World viruses and encephalitis induced by infection with New-World alphaviruses. Non-coding RNAs do not encode for proteins, but can modulate cellular response pathways in a myriad of ways. There are several classes of non-coding RNAs, some more well-studied than others. Much research has focused on the mRNA response to infection against alphaviruses, but analysis of non-coding RNA responses has been more limited until recently. This review covers what is known regarding host cell non-coding RNA responses in alphavirus infections and highlights gaps in the knowledge that future research should address.
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Jafari-Raddani F, Davoodi-Moghaddam Z, Yousefi AM, Ghaffari SH, Bashash D. An overview of long noncoding RNAs: Biology, functions, therapeutics, analysis methods, and bioinformatics tools. Cell Biochem Funct 2022; 40:800-825. [PMID: 36111699 DOI: 10.1002/cbf.3748] [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: 08/16/2022] [Revised: 09/05/2022] [Accepted: 09/06/2022] [Indexed: 12/15/2022]
Abstract
Long noncoding RNAs (lncRNAs) are a diverse class of RNAs whose functions are widespread in all branches of life and have been the focus of attention in the last decade. While a huge number of lncRNAs have been identified, there is still much work to be done and plenty to be learned. In the current review, we begin with the biogenesis and function of lncRNAs as they are involved in the different cellular processes from regulating the architecture of chromosomes to controlling translation and post-translation modifications. Questions on how overexpression, mutations, or deficiency of lncRNAs can affect the cellular status and result in the pathogenesis of various human diseases are responded to. Besides, we allocate an overview of several studies, concerning the application of lncRNAs either as diagnostic and prognostic biomarkers or novel therapeutics. We also introduce the currently available techniques to explore details of lncRNAs such as their function, cellular localization, and structure. In the last section, as exponentially growing data in this area need to be gathered and organized in comprehensive databases, we have a particular focus on presenting general and specialized databases. Taken together, with this review, we aim to provide the latest information on different aspects of lncRNAs to highlight their importance in physiopathologic states and take a step towards helping future studies.
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Affiliation(s)
- Farideh Jafari-Raddani
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zeinab Davoodi-Moghaddam
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir-Mohammad Yousefi
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed H Ghaffari
- Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Davood Bashash
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Chen T. Circulating Non-Coding RNAs as Potential Diagnostic Biomarkers in Hepatocellular Carcinoma. J Hepatocell Carcinoma 2022; 9:1029-1040. [PMID: 36132427 PMCID: PMC9484560 DOI: 10.2147/jhc.s380237] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 09/06/2022] [Indexed: 11/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is currently the second leading cause of cancer-related deaths worldwide, with high morbidity and mortality. The clinical diagnosis of HCC mainly depends on imaging technology, such as ultrasound and computed tomography, and serum biomarkers, such as alpha-fetoprotein (AFP). However, HCC is still hard to diagnose at an early stage due to the low sensitivity of the above mentioned traditional methods. Typically, HCC is diagnosed at an advanced stage when limited treatment options are available. It is urgent to identify effective biomarkers for the early diagnosis of HCC. Increasing evidence uncovered ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), could be used in HCC diagnosis. The aim of this review is to summarize our understanding of circulating miRNAs, lncRNAs and circRNAs as fluid-based non-invasive biomarkers, and aiming at providing new insights into the diagnosis of HCC.
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Affiliation(s)
- Tingsong Chen
- The Second Department of Oncology, the Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
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9
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Yan LR, Liu AR, Jiang LY, Wang BG. Non-coding RNA and hepatitis B virus-related hepatocellular carcinoma: A bibliometric analysis and systematic review. Front Med (Lausanne) 2022; 9:995943. [PMID: 36203765 PMCID: PMC9530602 DOI: 10.3389/fmed.2022.995943] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Accepted: 08/23/2022] [Indexed: 11/18/2022] Open
Abstract
Objectives A bibliometric analysis for non-coding RNA and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) was performed to describe international research status and visualize the research scope and emerging trends over the last two decades on this topic. Materials and methods Research data of non-coding RNA and HBV-related HCC were retrieved and extracted from the Web of Science Core Collection (WoSCC) database from 1 January 2003 to 13 June 2022 and then analyzed by means of bibliometric methods. A total of 1,036 articles published in this field were assessed for specific characteristics, including the year of publication, journal, author, institution, country/region, references, and keywords. VOSviewer was employed to perform co-authorship, co-occurrence, and co-citation analyses accompanied by constructing a visual network. Results Overall, 1,036 reports on non-coding RNA and HBV-related HCC from 2003 to 2022 were retrieved from WoSCC. The publication has gradually increased during the last two decades with 324 journals involved. Most research records (748 publications and 23,184 citations) were concentrated in China. A co-occurrence cluster analysis for the top 100 keywords was performed and four clusters were generated: (1) non-coding RNA as a molecular marker for the diagnosis and prognosis of HBV-related HCC; (2) dysregulation of non-coding RNA by hepatitis B virus X protein (HBx); (3) non-coding RNA affecting the biological behaviors of HBV-related HCC; and (4) epidemiological study for the effects of non-coding RNA on the risk of HBV-related HCC. Conclusion The publications and citations involved in non-coding RNA and HBV-related HCC have increased over the last two decades associated with many countries, institutions, and authors. Our study revealed current development trends, global cooperation models, basic knowledge, research hotspots, and emerging frontiers in this field.
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Affiliation(s)
- Li-rong Yan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang, China
| | - Ao-ran Liu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang, China
| | - Li-yue Jiang
- Tangdu Hospital of the Fourth Military Medical University, Xi’an, China
| | - Ben-gang Wang
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang, China
- Department of Hepatobiliary Surgery, Institute of General Surgery, The First Hospital of China Medical University, Shenyang, China
- *Correspondence: Ben-gang Wang,
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10
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Li HC, Yang CH, Lo SY. Long noncoding RNAs in hepatitis B virus replication and oncogenesis. World J Gastroenterol 2022; 28:2823-2842. [PMID: 35978877 PMCID: PMC9280728 DOI: 10.3748/wjg.v28.i25.2823] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 04/16/2022] [Accepted: 05/22/2022] [Indexed: 02/06/2023] Open
Abstract
Several diverse long noncoding RNAs (lncRNAs) have been identified to be involved in hepatitis B virus (HBV) replication and oncogenesis, especially those dysregulated in HBV-related hepatocellular carcinoma (HCC). Most of these dysregulated lncRNAs are modulated by the HBV X protein. The regulatory mechanisms of some lncRNAs in HBV replication and oncogenesis have been characterized. Genetic polymorphisms of several lncRNAs affecting HBV replication or oncogenesis have also been studied. The prognosis of HCC remains poor. It is important to identify novel tumor markers for early diagnosis and find more therapeutic targets for effective treatments of HCC. Some dysregulated lncRNAs in HBV-related HCC may become biomarkers for early diagnosis and/or the therapeutic targets of HCC. This mini-review summarizes these findings briefly, focusing on recent developments.
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Affiliation(s)
- Hui-Chun Li
- Department of Biochemistry, Tzu Chi University, Hualien 97004, Taiwan
| | - Chee-Hing Yang
- Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien 97004, Taiwan
| | - Shih-Yen Lo
- Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien 97004, Taiwan
- Department of Laboratory Medicine, Buddhist Tzu Chi General Hospital, Hualien 97004, Taiwan
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11
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Mo C, Wu J, Sui J, Deng Y, Li M, Cao Z, Hu Z, Huang J, Li S. Long non-coding RNA LINC01793 as a potential diagnostic biomarker of hepatitis B virus-related hepatocellular carcinoma. Clin Biochem 2022; 108:56-62. [PMID: 35760369 DOI: 10.1016/j.clinbiochem.2022.06.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 05/18/2022] [Accepted: 06/22/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND There is growing evidence that long non-coding RNAs (lncRNAs) play important roles in the progression of hepatocellular carcinoma (HCC) and may serve as diagnostic markers. This study investigates the diagnostic efficiency of the long intergenic non-protein-coding RNA 1793 (LINC01793) in hepatitis B virus (HBV)-related HCC. METHODS Bioinformatics methods were used to screen the aberrantly expressed lncRNAs in HCC tissues based on The Cancer Genome Atlas (TCGA). Quantitative reverse transcription polymerase chain reaction was performed to assess the expression of the candidate lncRNAs in tissues, cells and whole blood samples of patients with HBV-related HCC, liver cirrhosis (LC), chronic hepatitis (CHB), and healthy controls. Then, the correlations between LINC01793 and clinical characteristics were analyzed. Finally，the diagnostic value of LINC01793 was explored based on the receiver operating characteristic curve. RESULTS LINC01793 was remarkably upregulated in the HCC tissues and cells. It was highly expressed in the whole blood of the HBV-related HCC patients, unlike in that of the healthy controls and of the CHB and LC patients. Subsequent analysis revealed that high LINC01793 was related to the Barcelona Clinic Liver Cancer (P = 0.007), tumor invasion (P = 0.042), the number of tumors (P = 0.031) and serum level of alanine aminotransferase(p = 0.022). The areas under the curve of LINC01793, for distinguishing HCC from healthy controls, CHB and LC patients, were 0.824, 0.767 and 0.756, respectively. In addition, the combination of LINC01793 with alpha fetoprotein (AFP) had a stronger diagnostic value than LINC01793 or AFP alone in AFP-negative HCC patients. CONCLUSION High expression of LINC01793 is correlated with adverse clinical characteristics and can serve as a non-invasive biomarker of HCC.
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Affiliation(s)
- Cuiju Mo
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Junrong Wu
- Department of Laboratory Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Jingzhe Sui
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Yan Deng
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Meng Li
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Zhao Cao
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Zuojian Hu
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Junhui Huang
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Shan Li
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China.
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12
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Badowski C, He B, Garmire LX. Blood-derived lncRNAs as biomarkers for cancer diagnosis: the Good, the Bad and the Beauty. NPJ Precis Oncol 2022; 6:40. [PMID: 35729321 PMCID: PMC9213432 DOI: 10.1038/s41698-022-00283-7] [Citation(s) in RCA: 86] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 05/13/2022] [Indexed: 11/24/2022] Open
Abstract
Cancer ranks as one of the deadliest diseases worldwide. The high mortality rate associated with cancer is partially due to the lack of reliable early detection methods and/or inaccurate diagnostic tools such as certain protein biomarkers. Cell-free nucleic acids (cfNA) such as circulating long noncoding RNAs (lncRNAs) have been proposed as a new class of potential biomarkers for cancer diagnosis. The reported correlation between the presence of tumors and abnormal levels of lncRNAs in the blood of cancer patients has notably triggered a worldwide interest among clinicians and oncologists who have been actively investigating their potentials as reliable cancer biomarkers. In this report, we review the progress achieved ("the Good") and challenges encountered ("the Bad") in the development of circulating lncRNAs as potential biomarkers for early cancer diagnosis. We report and discuss the diagnostic performance of more than 50 different circulating lncRNAs and emphasize their numerous potential clinical applications ("the Beauty") including therapeutic targets and agents, on top of diagnostic and prognostic capabilities. This review also summarizes the best methods of investigation and provides useful guidelines for clinicians and scientists who desire conducting their own clinical studies on circulating lncRNAs in cancer patients via RT-qPCR or Next Generation Sequencing (NGS).
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Affiliation(s)
- Cedric Badowski
- University of Hawaii Cancer Center, Epidemiology, 701 Ilalo Street, Honolulu, HI, 96813, USA.
| | - Bing He
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48105, USA
| | - Lana X Garmire
- University of Hawaii Cancer Center, Epidemiology, 701 Ilalo Street, Honolulu, HI, 96813, USA.
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48105, USA.
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13
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Samudh N, Shrilall C, Arbuthnot P, Bloom K, Ely A. Diversity of Dysregulated Long Non-Coding RNAs in HBV-Related Hepatocellular Carcinoma. Front Immunol 2022; 13:834650. [PMID: 35154157 PMCID: PMC8831247 DOI: 10.3389/fimmu.2022.834650] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 01/10/2022] [Indexed: 12/13/2022] Open
Abstract
Infection with the hepatitis B virus (HBV) continues to pose a major threat to public health as approximately 292 million people worldwide are currently living with the chronic form of the disease, for which treatment is non-curative. Chronic HBV infections often progress to hepatocellular carcinoma (HCC) which is one of the world’s leading causes of cancer-related deaths. Although the process of hepatocarcinogenesis is multifaceted and has yet to be fully elucidated, several studies have implicated numerous long non-coding RNAs (lncRNAs) as contributors to the development of HCC. These host-derived lncRNAs, which are often dysregulated as a consequence of viral infection, have been shown to function as signals, decoys, guides, or scaffolds, to modulate gene expression at epigenetic, transcriptional, post-transcriptional and even post-translational levels. These lncRNAs mainly function to promote HBV replication and oncogene expression or downregulate tumor suppressors. Very few lncRNAs are known to suppress tumorigenesis and these are often downregulated in HCC. In this review, we describe the mechanisms by which lncRNA dysregulation in HBV-related HCC promotes tumorigenesis and cancer progression.
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Affiliation(s)
- Nazia Samudh
- Wits/South African Medical Research Council (SAMRC) Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Creanne Shrilall
- Wits/South African Medical Research Council (SAMRC) Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Patrick Arbuthnot
- Wits/South African Medical Research Council (SAMRC) Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Kristie Bloom
- Wits/South African Medical Research Council (SAMRC) Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Abdullah Ely
- Wits/South African Medical Research Council (SAMRC) Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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14
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Wang X, Kang M, Liu C, Lin T, Han X, Jiang X. Current State and Progress of Research on the Role of lncRNA in HBV-Related Liver Cancer. Front Cell Infect Microbiol 2021; 11:714895. [PMID: 34869051 PMCID: PMC8636595 DOI: 10.3389/fcimb.2021.714895] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 11/01/2021] [Indexed: 01/04/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a malignant tumor with the highest mortality rate in the world, and hepatitis B virus (HBV) plays an important role in its development. Long noncoding RNA (lncRNA) is highly related to the inactivation of tumor suppressor genes and the activation of oncogenes in HCC. Researchers have used high-throughput sequencing technology to identify many noncoding transcripts related to the development of HCC and have studied the interaction between these transcripts and DNA, RNA, or protein to determine the relevant mechanism in the development of HCC. In general, the research on lncRNA represents a new field of cancer research, and the imbalance in lncRNA plays an pivotal role in the occurrence of liver cancer. In this review, we summarize some of the dysfunctional lncRNAs in human HCC associated with HBV infection. Their regulatory pathways, functions, and potential molecular mechanisms in the occurrence and development of HCC are discussed.
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Affiliation(s)
- Xueke Wang
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, China
| | - Meisong Kang
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, China
| | - Chun Liu
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, China
| | - Ting Lin
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, China
| | - Xiao Han
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, China
| | - Xiwen Jiang
- DAAN Gene Co., Ltd. of Sun Yat-sen University, Guangzhou, China
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15
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Huang JY, Wang SY, Lin Y, Yi HC, Niu JJ. The Diagnostic Performance of lncRNAs from Blood Specimens in Patients with Hepatocellular Carcinoma: A Meta-Analysis. Lab Med 2021; 52:64-73. [PMID: 32700735 DOI: 10.1093/labmed/lmaa050] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE Long noncoding RNAs (lncRNAs) are widely involved in the carcinogenesis and development of cancers. We conducted a meta-analysis to evaluate the diagnostic performance of lncRNAs in hepatocellular carcinoma (HCC). METHODS After the inclusion and exclusion process, relevant information was extracted. Heterogeneity between studies was evaluated, and data synthesis was conducted by employing a bivariate random-effects model. RESULTS In total, 20 eligible studies were enrolled. The pooled sensitivity and specificity were 0.86 (95% confidence interval [CI], 0.80-0.90) and 0.88 (95% CI, 0.82-0.92), respectively. The pooled positive likelihood ratio, pooled negative likelihood ratio, and pooled diagnostic odds ratio were 7.1 (95% CI, 4.9-10.2), 0.16 (95% CI, 0.11-0.23), and 44 (95% CI, 25-79), respectively. The results of the linear regression method and visual inspection of the Deeks funnel plot did not indicate significant publication bias. CONCLUSION Our meta-analysis suggested that lncRNAs have high diagnostic performance for HCC and have the potential for clinical application.
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Affiliation(s)
- Jing-Yi Huang
- Clinical Laboratory, Xiamen Branch of Zhongshan Hospital, Fudan University, Xiamen, Fujian Province, China
| | - Si-Yu Wang
- Center of Clinical Laboratory, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, China
| | - Yong Lin
- Center of Clinical Laboratory, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, China
| | - Huo-Chun Yi
- Center of Clinical Laboratory, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, China
| | - Jian-Jun Niu
- Center of Clinical Laboratory, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, China
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16
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Alfano V, Zeisel MB, Levrero M, Guerrieri F. The lncRNAs in HBV-Related HCCs: Targeting Chromatin Dynamics and Beyond. Cancers (Basel) 2021; 13:3115. [PMID: 34206504 PMCID: PMC8268133 DOI: 10.3390/cancers13133115] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/18/2021] [Accepted: 06/19/2021] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) represents the fourth leading and fastest rising cause of cancer death (841,000 new cases and 782,000 deaths annually), and hepatitis B (HBV), with 250 million people chronically infected at risk of developing HCC, accounts for >50% of the cases worldwide. Long non-coding RNAs (lncRNAs), untranslated transcripts longer than 200 nucleotides, are implicated in gene regulation at the transcriptional and post-transcriptional levels, exerting their activities both in the nuclear and cytoplasmic compartments. Thanks to high-throughput sequencing techniques, several lncRNAs have been shown to favor the establishment of chronic HBV infection, to change the host transcriptome to establish a pro-carcinogenic environment, and to directly participate in HCC development and progression. In this review, we summarize current knowledge on the role of lncRNAs in HBV infection and HBV-related liver carcinogenesis and discuss the potential of lncRNAs as predictive or diagnostic biomarkers.
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Affiliation(s)
- Vincenzo Alfano
- Cancer Research Center of Lyon (CRCL), UMR Inserm 1052 CNRS 5286 Mixte CLB, Université de Lyon 1 (UCBL1), 69003 Lyon, France; (V.A.); (M.B.Z.)
| | - Mirjam B. Zeisel
- Cancer Research Center of Lyon (CRCL), UMR Inserm 1052 CNRS 5286 Mixte CLB, Université de Lyon 1 (UCBL1), 69003 Lyon, France; (V.A.); (M.B.Z.)
| | - Massimo Levrero
- Cancer Research Center of Lyon (CRCL), UMR Inserm 1052 CNRS 5286 Mixte CLB, Université de Lyon 1 (UCBL1), 69003 Lyon, France; (V.A.); (M.B.Z.)
- Hospices Civils de Lyon, Hôpital Croix Rousse, Service d’Hépato-Gastroentérologie, 69004 Lyon, France
- Department of Medicine SCIAC, University of Rome La Sapienza, 00161 Rome, Italy
| | - Francesca Guerrieri
- Cancer Research Center of Lyon (CRCL), UMR Inserm 1052 CNRS 5286 Mixte CLB, Université de Lyon 1 (UCBL1), 69003 Lyon, France; (V.A.); (M.B.Z.)
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17
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Song T, Li L, Wu S, Liu Y, Guo C, Wang W, Dai L, Zhang T, Wu H, Su B. Peripheral Blood Genetic Biomarkers for the Early Diagnosis of Hepatocellular Carcinoma. Front Oncol 2021; 11:583714. [PMID: 33777736 PMCID: PMC7991745 DOI: 10.3389/fonc.2021.583714] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 02/18/2021] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has high mortality. Biomarkers related to HCC, such as alpha-fetoprotein, and imaging technology, such as ultrasound and computed tomography, have been used to screen and monitor HCC, but HCC is still difficult to diagnose effectively in the early stage due to the low sensitivity of the above mentioned traditional methods. There is an urgent need for noninvasive biomarkers to facilitate the screening and early diagnosis of HCC. With the advancement of next-generation sequencing, genetic biomarkers are becoming the core of cancer diagnosis. Genetic biomarkers such as peripheral blood circulating tumor DNA, microRNAs, long noncoding RNAs, circular RNAs, and exosomes have become the focus of early HCC diagnostics. HCC genetic biomarkers have been implemented in clinical practice. In this review, we describe the available literature on peripheral blood genetic biomarkers in the diagnosis of early HCC.
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Affiliation(s)
- Ting Song
- Department of Infectious Diseases and Medical Immunology, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory for HIV/AIDS Research, Beijing, China.,Department of Hepatology, The Sixth People's Hospital of Qingdao, Qingdao, China
| | - Li Li
- Department of Infectious Diseases and Medical Immunology, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory for HIV/AIDS Research, Beijing, China
| | - Shaobo Wu
- Center of Transfusion-Transmitted Infectious Diseases, Institute of Blood Transfusion, Chinese Academy of Medical Sciences (CAMS), Chengdu, China
| | - Yan Liu
- Department of Infectious Diseases and Medical Immunology, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory for HIV/AIDS Research, Beijing, China
| | - Caiping Guo
- Department of Infectious Diseases and Medical Immunology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Wen Wang
- Department of Infectious Diseases and Medical Immunology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Lili Dai
- Department of Infectious Diseases and Medical Immunology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Tong Zhang
- Department of Infectious Diseases and Medical Immunology, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory for HIV/AIDS Research, Beijing, China
| | - Hao Wu
- Department of Infectious Diseases and Medical Immunology, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory for HIV/AIDS Research, Beijing, China
| | - Bin Su
- Department of Infectious Diseases and Medical Immunology, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory for HIV/AIDS Research, Beijing, China
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18
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Zhou X, Yuan Q, Zhang C, Dai Z, Du C, Wang H, Li X, Yang S, Zhao A. Inhibition of Japanese encephalitis virus proliferation by long non-coding RNA SUSAJ1 in PK-15 cells. Virol J 2021; 18:29. [PMID: 33509198 PMCID: PMC7841041 DOI: 10.1186/s12985-021-01492-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 01/07/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Japanese encephalitis virus is a mosquito-borne neurotropic flavivirus that causes acute viral encephalitis in humans. Pigs are crucial amplifier host of JEV. Recently, increasing evidence has shown that long non-coding RNAs (lncRNAs) play important roles in virus infection. METHODS JEV proliferation was evaluated after overexpression or knockdown of lncRNA-SUSAJ1 using western blotting and reverse-transcription polymerase chain reaction (RT-PCR). C-C chemokine receptor type 1 (CCR1) was found to regulate the expression of lncRNA-SUSAJ1 by inhibitors screen. The expression of lncRNA-SUSAJ1 was detected using RT-PCR after overexpression or knockdown of transcription factor SP1. In addition, the enrichments of transcription factor SP1 on the promoter of lncRNA-SUSAJ1 were analyzed by chromatin immunoprecipitation. RESULTS In this study, we demonstrated that swine lncRNA-SUSAJ1 could suppress JEV proliferation in PK-15 cells. We also found that CCR1 inhibited the expression of lncRNA-SUSAJ1 via the transcription factor SP1. In addition, knockdown of CCR1 could upregulated the expression of SP1 and lncRNA-SUSAJ1, resulting in resistance to JEV proliferation. CONCLUSIONS These findings illustrate the importance of lncRNAs in virus proliferation, and reveal how this virus regulates lncRNAs in host cells to promote its proliferation.
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Affiliation(s)
- Xiaolong Zhou
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China
| | - Qiongyu Yuan
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China
| | - Chen Zhang
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China
| | - Zhenglie Dai
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China
| | - Chengtao Du
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China
| | - Han Wang
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China
| | - Xiangchen Li
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China
| | - Songbai Yang
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China.
| | - Ayong Zhao
- Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology . College of Veterinary Medicine, Zhejiang Agriculture and Forest University, 666 Wusu Road, Hangzhou, 311300, China.
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19
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Sukowati CHC, Cabral LKD, Tiribelli C, Pascut D. Circulating Long and Circular Noncoding RNA as Non-Invasive Diagnostic Tools of Hepatocellular Carcinoma. Biomedicines 2021; 9:90. [PMID: 33477833 PMCID: PMC7832835 DOI: 10.3390/biomedicines9010090] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/14/2021] [Accepted: 01/16/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide, partially due to late diagnosis of the disease. Growing evidence in the field of biomarker discovery has shown the promising use of nucleic acid in the early detection of many cancers, including HCC. Here, we review data on how various long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) could be used as a diagnostic tool for HCC being differentially expressed in HCC compared to non-HCC patients. These non-coding RNAs (ncRNAs) showed high stability in the blood being present as free-circulating molecules or encapsulated into exosomes. This review reports some recent evidence on the use of lncRNAs and circRNAs as possible diagnostic biomarkers for HCC. Further, their pathophysiological mechanism in liver carcinogenesis was also described, elucidating the complex regulatory networks making these ncRNAs of particular relevance for the study of liver malignancy cancer.
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Affiliation(s)
- Caecilia H. C. Sukowati
- Fondazione Italiana Fegato ONLUS, AREA Science Park, Campus Basovizza, SS14, km 163.5, 34149 Trieste, Italy; (C.H.C.S.); (L.K.D.C.); (C.T.)
| | - Loraine Kay D. Cabral
- Fondazione Italiana Fegato ONLUS, AREA Science Park, Campus Basovizza, SS14, km 163.5, 34149 Trieste, Italy; (C.H.C.S.); (L.K.D.C.); (C.T.)
- Doctoral School in Molecular Biomedicine, University of Trieste, 34100 Trieste, Italy
| | - Claudio Tiribelli
- Fondazione Italiana Fegato ONLUS, AREA Science Park, Campus Basovizza, SS14, km 163.5, 34149 Trieste, Italy; (C.H.C.S.); (L.K.D.C.); (C.T.)
| | - Devis Pascut
- Fondazione Italiana Fegato ONLUS, AREA Science Park, Campus Basovizza, SS14, km 163.5, 34149 Trieste, Italy; (C.H.C.S.); (L.K.D.C.); (C.T.)
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20
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Fang X, Wang D, Pu K, Zhang Z, Wang H, Wang H, Zheng Y, Wang Y, Guan Q, Zhou Y. Diagnostic value of circulating lncRNAs as biomarkers of digestive system cancers: A systematic review and meta-analysis. Expert Rev Mol Diagn 2020; 20:1051-1062. [PMID: 33138648 DOI: 10.1080/14737159.2020.1822169] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Accepted: 09/08/2020] [Indexed: 12/23/2022]
Abstract
OBJECTIVE This meta-analysis aims to explore the diagnostic value and accuracy of circulating lncRNAs as biomarkers of digestive system tumors. METHODS PubMed, Embase, Cochrane Library, and Web of science were searched for relevant articles that were published before April 2019, and a meta-analysis was conducted. RESULTS 52 studies with 63 lncRNAs were discussed in the meta-analysis. The pooled sensitivity and specificity of diagnosis were 0.80 (95% CI: 0.79-0.81) and 0.76 (95% CI: 0.75-0.77), respectively. The pooled DOR (the diagnostic odds ratio) was 15.63 (95% CI: 12.77-19.12), and the overall AUC (the area under the curve) was 0.87. Besides, subgroup analyzes showed that the DOR and AUC of large sample sizes (>80), multiple lncRNAs, serum-based lncRNAs, and downregulation group were superior to those of small sample sizes (≤80), single lncRNA, plasma-based lncRNAs, and upregulation group, respectively. The current data also highlight that the diagnostic accuracy of circulating lncRNAs in the case of colorectal cancer was higher than gastric cancer, hepatocellular carcinoma, esophageal carcinoma, and pancreatic cancer. And there is no difference in the perspective of geographical regions. CONCLUSION The circulating lncRNAs have high diagnostic value and accuracy in digestive system cancers and may serve as potential biomarkers.
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Affiliation(s)
- Xidong Fang
- The First Clinical Medical College, Lanzhou University , Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University , Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University , Lanzhou, China
| | - Dongke Wang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Ke Pu
- The First Clinical Medical College, Lanzhou University , Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University , Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University , Lanzhou, China
| | - Zhaoyu Zhang
- Department of Physiology and Pathophysiology, Peking University Health Science Center , Beijing, China
| | - Huiying Wang
- Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University , Changsha, Hunan, China
- National Clinical Research Center for Metabolic Diseases , Changsha, Hunan, China
| | - Haojia Wang
- The First Clinical Medical College, Lanzhou University , Lanzhou, China
| | - Ya Zheng
- The First Clinical Medical College, Lanzhou University , Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University , Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University , Lanzhou, China
| | - Yuping Wang
- The First Clinical Medical College, Lanzhou University , Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University , Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University , Lanzhou, China
| | - Quanlin Guan
- The First Clinical Medical College, Lanzhou University , Lanzhou, China
- Department of Oncology Surgery, The First Hospital of Lanzhou University , Lanzhou, China
| | - Yongning Zhou
- The First Clinical Medical College, Lanzhou University , Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University , Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University , Lanzhou, China
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21
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Cao P, Jin Q, Feng L, Li H, Qin G, Zhou G. Emerging roles and potential clinical applications of noncoding RNAs in hepatocellular carcinoma. Semin Cancer Biol 2020; 75:136-152. [PMID: 32931952 DOI: 10.1016/j.semcancer.2020.09.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 08/24/2020] [Accepted: 09/01/2020] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma(HCC) is one of the most common forms of cancer, and accounts for a high proportion of cancer-associated deaths. Growing evidences have demonstrated that non- protein-coding regions of the genome could give rise to transcripts, termed noncoding RNA (ncRNA), that form novel functional layers of the cellular activity. ncRNAs are implicated in different molecular mechanisms and functions at transcriptional, translational and post-translational levels. An increasing number of studies have demonstrated a complex array of molecular and cellular functions of ncRNAs in different stages of the HCC tumorigenesis, either in an oncogenic or tumor-suppressive manner. As a result, several pre-clinical studies have highlighted the great potentials of ncRNAs as novel biomarkers for cancer diagnosis or therapeutics in targeting HCC progression. In this review, we briefly described the characteristics of several representative ncRNAs and summarized the latest findings of their roles and mechanisms in the development of HCC, in order to better understand the cancer biology and their potential clinical applications in this malignancy.
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Affiliation(s)
- Pengbo Cao
- State Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Institute of Radiation Medicine, Beijing, China
| | - Qian Jin
- State Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Institute of Radiation Medicine, Beijing, China
| | - Lan Feng
- State Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Institute of Radiation Medicine, Beijing, China
| | - Haibei Li
- Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin Institute of Environmental & Operational Medicine, Tianjin City, China
| | - Geng Qin
- State Key Laboratory of Rare Earth Resources Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun City, China
| | - Gangqiao Zhou
- State Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Institute of Radiation Medicine, Beijing, China; Collaborative Innovation Center for Personalized Cancer Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing City, China; Medical College, Guizhou University, Guiyang City, China.
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Zhang H, Chen X, Zhang J, Wang X, Chen H, Liu L, Liu S. Long non‑coding RNAs in HBV‑related hepatocellular carcinoma (Review). Int J Oncol 2019; 56:18-32. [PMID: 31746420 DOI: 10.3892/ijo.2019.4909] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Accepted: 09/02/2019] [Indexed: 12/25/2022] Open
Abstract
Hepatitis B virus (HBV)‑related hepatocellular carcinoma (HCC) is a global health problem that accounts for more than half of total liver cancer cases in developing countries. Despite the growing number of researches conducted, the molecular mechanism underlying the development of HCC remains elusive. Long non‑coding RNAs (lncRNAs), which are non‑coding RNAs >200 nt in length that were previously considered to be transcriptional noise, have been found to be dysregulated in HBV‑related HCC with the help of high‑throughput omics techniques. Subsequent investigations revealed that aberrant expression of lncRNAs may affect the risk of HBV‑related HCC through diverse mechanisms, including epigenetic silencing of transcriptional activation, alternative splicing, molecular sponging, modulating protein stability, and by serving as precursors of miRNAs. Although the sensitivity and specificity of lncRNAs must be further validated, a number of circulating lncRNAs have been identified as useful biomarkers for HBV‑related HCC. In addition to these findings, recent studies also unveiled that certain genetic polymorphisms in lncRNAs may affect the occurrence and prognosis of HBV‑related HCC. The aim of the present review was to provide an overview of the mechanisms underlying the involvement of lncRNAs in HBV‑related HCC. Subsequently, lncRNAs found to be dysregulated in HBV‑related HCC were focused on and current findings on circulating lncRNAs and their genetic polymorphisms were discussed.
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Affiliation(s)
- Hao Zhang
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Sichuan 610000, P.R. China
| | - Xuebing Chen
- Department of Infectious Diseases, People's Hospital of Deyang City, Deyang, Sichuan 618000, P.R. China
| | - Jian Zhang
- Department of Pathology, People's Hospital of Deyang City, Deyang, Sichuan 618000, P.R. China
| | - Xianwei Wang
- Department of Pathology, People's Hospital of Deyang City, Deyang, Sichuan 618000, P.R. China
| | - Huijuan Chen
- Department of Pathology, People's Hospital of Deyang City, Deyang, Sichuan 618000, P.R. China
| | - Lin Liu
- Department of Pathology, People's Hospital of Deyang City, Deyang, Sichuan 618000, P.R. China
| | - Shanling Liu
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Sichuan 610000, P.R. China
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23
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Wang JJ, Huang YQ, Song W, Li YF, Wang H, Wang WJ, Huang M. Comprehensive analysis of the lncRNA‑associated competing endogenous RNA network in breast cancer. Oncol Rep 2019; 42:2572-2582. [PMID: 31638237 PMCID: PMC6826329 DOI: 10.3892/or.2019.7374] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2018] [Accepted: 09/19/2019] [Indexed: 12/14/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) have been confirmed to be potential prognostic markers in a variety of cancers and to interact with microRNAs (miRNAs) as competing endogenous RNAs (ceRNAs) to regulate target gene expression. However, the role of lncRNA‑mediated ceRNAs in breast cancer (BC) remains unclear. In the present study, a ceRNA network was generated to explore their role in BC. The expression profiles of mRNAs, miRNAs and lncRNAs in 1,109 BC tissues and 113 normal breast tissues were obtained from The Cancer Genome Atlas database (TCGA). A total of 3,198 differentially expressed (DE) mRNAs, 150 differentially DEmiRNAs and 1,043 DElncRNAs were identified between BC and normal tissues. A lncRNA‑miRNA‑mRNA network associated with BC was successfully constructed based on the combined data obtained from RNA databases, and comprised 97 lncRNA nodes, 24 miRNA nodes and 74 mRNA nodes. The biological functions of the 74 DEmRNAs were further investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results demonstrated that the DEmRNAs were significantly enriched in two GO biological process categories; the main biological process enriched term was 'positive regulation of GTPase activity'. By KEGG analysis, four key enriched pathways were obtained, including the 'MAPK signaling pathway', the 'Ras signaling pathway', 'prostate cancer', and the 'FoxO signaling pathway'. Kaplan‑Meier survival analysis revealed that six DElncRNAs (INC AC112721.1, LINC00536, MIR7‑3HG, ADAMTS9‑AS1, AL356479.1 and LINC00466), nine DEmRNAs (KPNA2, RACGAP1, SHCBP1, ZNF367, NTRK2, ORS1, PTGS2, RASGRP1 and SFRP1) and two DEmiRNAs (hsa‑miR‑301b and hsa‑miR‑204) had significant effects on overall survival in BC. The present results demonstrated the aberrant expression of INC AC112721.1, AL356479.1, LINC00466 and MIR7‑3HG in BC, indicating their potential prognostic role in patients with BC.
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Affiliation(s)
- Jing-Jing Wang
- Department of Oncology, Taizhou Hospital of Traditional Chinese Medicine, Taizhou, Jiangsu 225300, P.R. China
| | - Yue-Qing Huang
- Department of General Practice, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215001, P.R. China
| | - Wei Song
- Department of Intervention and Vascular Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215001, P.R. China
| | - Yi-Fan Li
- Department of Oncology, Binzhou People's Hospital, Binzhou, Shandong 256600, P.R. China
| | - Han Wang
- Department of Oncology, Jining Cancer Hospital, Jining, Shandong 272000, P.R. China
| | - Wen-Jie Wang
- Department of Radio‑Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215001, P.R. China
| | - Min Huang
- Department of General Practice, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215001, P.R. China
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Pardini B, Sabo AA, Birolo G, Calin GA. Noncoding RNAs in Extracellular Fluids as Cancer Biomarkers: The New Frontier of Liquid Biopsies. Cancers (Basel) 2019; 11:E1170. [PMID: 31416190 PMCID: PMC6721601 DOI: 10.3390/cancers11081170] [Citation(s) in RCA: 136] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 08/04/2019] [Accepted: 08/10/2019] [Indexed: 02/06/2023] Open
Abstract
The last two decades of cancer research have been devoted in two directions: (1) understanding the mechanism of carcinogenesis for an effective treatment, and (2) improving cancer prevention and screening for early detection of the disease. This last aspect has been developed, especially for certain types of cancers, thanks also to the introduction of new concepts such as liquid biopsies and precision medicine. In this context, there is a growing interest in the application of alternative and noninvasive methodologies to search for cancer biomarkers. The new frontiers of the research lead to a search for RNA molecules circulating in body fluids. Searching for biomarkers in extracellular body fluids represents a better option for patients because they are easier to access, less painful, and potentially more economical. Moreover, the possibility for these types of samples to be taken repeatedly, allows a better monitoring of the disease progression or treatment efficacy for a better intervention and dynamic treatment of the patient, which is the fundamental basis of personalized medicine. RNA molecules, freely circulating in body fluids or packed in microvesicles, have all the characteristics of the ideal biomarkers owing to their high stability under storage and handling conditions and being able to be sampled several times for monitoring. Moreover, as demonstrated for many cancers, their plasma/serum levels mirror those in the primary tumor. There are a large variety of RNA species noncoding for proteins that could be used as cancer biomarkers in liquid biopsies. Among them, the most studied are microRNAs, but recently the attention of the researcher has been also directed towards Piwi-interacting RNAs, circular RNAs, and other small noncoding RNAs. Another class of RNA species, the long noncoding RNAs, is larger than microRNAs and represents a very versatile and promising group of molecules which, apart from their use as biomarkers, have also a possible therapeutic role. In this review, we will give an overview of the most common noncoding RNA species detectable in extracellular fluids and will provide an update concerning the situation of the research on these molecules as cancer biomarkers.
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Affiliation(s)
- Barbara Pardini
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy.
- Unit of Molecular Epidemiology and Exposome, Italian Institute for Genomic Medicine (IIGM), 10126 Turin, Italy.
| | - Alexandru Anton Sabo
- Department of Pediatrics, Marie Curie Emergency Clinical Hospital for Children, 077120 Bucharest, Romania
| | - Giovanni Birolo
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy
- Unit of Molecular Epidemiology and Exposome, Italian Institute for Genomic Medicine (IIGM), 10126 Turin, Italy
| | - George Adrian Calin
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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Liu H, Zhao P, Jin X, Zhao Y, Chen Y, Yan T, Wang J, Wu L, Sun Y. A 9‑lncRNA risk score system for predicting the prognosis of patients with hepatitis B virus‑positive hepatocellular carcinoma. Mol Med Rep 2019; 20:573-583. [PMID: 31115573 PMCID: PMC6579967 DOI: 10.3892/mmr.2019.10262] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Accepted: 12/28/2018] [Indexed: 12/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and can be induced by hepatitis B virus (HBV) infection. The aim of the present study was to screen prognosis‑associated long noncoding RNAs (lncRNAs) and construct a risk score system for the disease. The RNA‑sequencing data of patients with HCC (including 100 HCC samples and 26 normal samples) were extracted from The Cancer Genome Atlas (TCGA) database. In addition, GSE55092, GSE19665 and GSE10186 datasets were downloaded from the Gene Expression Omnibus database. Combined with weighted gene co‑expression network analysis, the identification and functional annotation of stable modules was performed. Using the MetaDE package, the consensus differentially expressed RNAs (DE‑RNAs) were analyzed. To construct a risk score system, prognosis‑associated lncRNAs and the optimal lncRNA combination were separately analyzed by survival and penalized packages. Finally, pathway enrichment analysis for the nodes in an lncRNA‑mRNA network was conducted via Gene Set Enrichment Analysis. A total of four stable modules and 3,051 consensus DE‑RNAs were identified. The stable modules were significantly associated with the histological grades of HCC, tumor, node and metastasis stage, pathological stage, recurrence and exposure to radiation therapy. A 9‑lncRNA optimal combination [DiGeorge syndrome critical region gene 9, glucosidase, β, acid 3 (GBA3), HLA complex group 4, N‑acetyltransferase 8B, neighbor of breast cancer 1 gene 2, prostate androgen‑regulated transcript 1, ret finger protein like 1 antisense RNA 1, solute carrier family 22 member 18 antisense and T‑cell leukemia/lymphoma 6] was selected from the 14 prognosis‑associated lncRNAs, and was further supported by the validation dataset, GSE10186. The lncRNA‑mRNA co‑expression network revealed lncRNA GBA3 as a positive regulator of phosphoenolpyruvate carboxykinase 2, an important enzyme in the metabolic pathway of gluconeogenesis. A risk score system was established based on the optimal 9 lncRNAs, which may be valuable for predicting the prognosis of patients with HBV‑positive HCC and improving understanding of mechanisms associated with the pathogenesis of this disease. On the contrary, a larger, independent cohort of patients is required to further validate the risk‑score system.
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Affiliation(s)
- Honghong Liu
- International Center for Liver Disease Treatment, 302 Hospital of The People's Liberation Army, Beijing 100039, P.R. China
| | - Ping Zhao
- International Center for Liver Disease Treatment, 302 Hospital of The People's Liberation Army, Beijing 100039, P.R. China
| | - Xueyuan Jin
- International Center for Liver Disease Treatment, 302 Hospital of The People's Liberation Army, Beijing 100039, P.R. China
| | - Yanling Zhao
- Department of Pharmacy, 302 Hospital of The People's Liberation Army, Beijing 100039, P.R. China
| | - Yongqian Chen
- International Center for Liver Disease Treatment, 302 Hospital of The People's Liberation Army, Beijing 100039, P.R. China
| | - Tao Yan
- International Center for Liver Disease Treatment, 302 Hospital of The People's Liberation Army, Beijing 100039, P.R. China
| | - Jianjun Wang
- International Center for Liver Disease Treatment, 302 Hospital of The People's Liberation Army, Beijing 100039, P.R. China
| | - Liang Wu
- International Center for Liver Disease Treatment, 302 Hospital of The People's Liberation Army, Beijing 100039, P.R. China
| | - Yongqiang Sun
- Integrative Medical Center, 302 Hospital of The People's Liberation Army, Beijing 100039, P.R. China
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Balaceanu LA. Biomarkers vs imaging in the early detection of hepatocellular carcinoma and prognosis. World J Clin Cases 2019; 7:1367-1382. [PMID: 31363465 PMCID: PMC6656675 DOI: 10.12998/wjcc.v7.i12.1367] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 04/07/2019] [Accepted: 05/03/2019] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the 5th most frequently diagnosed cancer in the world, according to the World Health Organization. The incidence of HCC is between 3/100000 and 78.1/100000, with a high incidence reported in areas with viral hepatitis B and hepatitis C, thus affecting Asia and Africa predominantly. Several international clinical guidelines address HCC diagnosis and are structured according to the geographical area involved. All of these clinical guidelines, however, share a foundation of diagnosis by ultrasound surveillance and contrast imaging techniques, particularly computed tomography, magnetic resonance imaging, and sometimes contrast-enhanced ultrasound. The primary objective of this review was to systematically summarize the recent published studies on the clinical utility of serum biomarkers in the early diagnosis of HCC and for the prognosis of this disease.
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Affiliation(s)
- Lavinia Alice Balaceanu
- Department of Internal Medicine, Carol Davila University of Medicine and Pharmacy, Sf. Ioan Clinical Emergency Hospital, Bucharest 42122, Romania
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27
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Song W, Wang J, Liu H, Zhu C, Xu F, Qian L, Shen Z, Zhu J, Yin S, Qin J, Chen L, Wu D, Nashan B, Shan G, Xiao W, Zhou Y. Effects of LncRNA Lnc-LIF-AS on cell proliferation, migration and invasion in a human cervical cancer cell line. Cytokine 2019; 120:165-175. [PMID: 31085454 DOI: 10.1016/j.cyto.2019.05.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 05/02/2019] [Accepted: 05/05/2019] [Indexed: 12/11/2022]
Abstract
This study explored the effect of LncRNA Lnc-LIF-AS on cell proliferation, migration and invasion in the human cervical cancer (HCC) cell line SiHa. SiHa cells had the lowest expression of Lnc-LIF-AS in the 4 human cervical cancer cell lines (SiHa, ME-180, C-33A and HeLa) and were transfected and divided into the SiHa/con (transfected with pMIGRI) cell group, SiHa/Lnc-LIF-AS (transfected with pMIGRI-Lnc-LIF-AS) cell group, and SiHa/Lnc-LIF-AS-DN (transfected with pMIGRI-Lnc-LIF-AS-DN, in which the sequences overlapping with LIF mRNA was deleted) cell group. Overexpression of Lnc-LIF-AS could promote the proliferation, colony formation, invasion and migration in SiHa and ME-180 cells. And the low expression of Lnc-LIF-AS suppress the proliferation, colony formation invasion and migration in HeLa cells when the Lnc-LIF-AS expression has been suppressed. In the SiHa/Lnc-LIF-AS cells group, the cell cycle was mainly halted in the S phase and overexpression of Lnc-LIF-AS had no effect on the apoptosis of SiHa cells. Overexpression of Lnc-LIF-AS could promote the secretion of LIF in SiHa cells, and the supernatant from SiHa/Lnc-LIF-AS cells could promote cell proliferation in the SiHa/con cells. The STAT3 inhibitor could inhibit cell proliferation in the SiHa/Lnc-LIF-AS cells. The expression level of Lnc-LIF-AS in cervical cancer tissues was higher than that in normal tissues and the expression level of Lnc-LIF-AS was positively correlated with the level of LIF. In the SiHa/con and SiHa/Lnc-LIF-AS-DN cell groups, there were no significant differences in cell proliferation, cell migration and cell invasion. The overexpression of Lnc-LIF-AS can promote cell proliferation, migration and invasion in cervical cancer cells, and the core function domain of this lncRNA was located in the overlapping a 3'-UTR base sequence of LIF mRNA.
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Affiliation(s)
- Weiguo Song
- Department of Obstetrics and Gynecology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, China
| | - Juan Wang
- Department of Obstetrics and Gynecology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, China
| | - Hanyuan Liu
- Department of Obstetrics and Gynecology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, China
| | - Chenchen Zhu
- Department of Obstetrics and Gynecology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, China
| | - Fei Xu
- Department of Obstetrics and Gynecology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, China
| | - Lili Qian
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science & Technology of China, Anhui Provincial Hospital, Hefei, Anhui Province 230001, China
| | - Zhen Shen
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science & Technology of China, Anhui Provincial Hospital, Hefei, Anhui Province 230001, China
| | - Jing Zhu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science & Technology of China, Anhui Provincial Hospital, Hefei, Anhui Province 230001, China
| | - Shuai Yin
- Organ Transplantation Center, The First Affiliated Hospital of University of Science & Technology of China, Anhui Provincial Hospital, Hefei 230001, China
| | - Jiwei Qin
- Organ Transplantation Center, The First Affiliated Hospital of University of Science & Technology of China, Anhui Provincial Hospital, Hefei 230001, China
| | - Liang Chen
- Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
| | - Dabao Wu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science & Technology of China, Anhui Provincial Hospital, Hefei, Anhui Province 230001, China
| | - Björn Nashan
- Organ Transplantation Center, The First Affiliated Hospital of University of Science & Technology of China, Anhui Provincial Hospital, Hefei 230001, China
| | - Ge Shan
- Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
| | - Weihua Xiao
- Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
| | - Ying Zhou
- Department of Obstetrics and Gynecology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, China.
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Motawi TMK, El-Maraghy SA, Sabry D, Mehana NA. The expression of long non coding RNA genes is associated with expression with polymorphisms of HULC rs7763881 and MALAT1 rs619586 in hepatocellular carcinoma and HBV Egyptian patients. J Cell Biochem 2019; 120:14645-14656. [PMID: 31009106 DOI: 10.1002/jcb.28726] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 01/21/2019] [Accepted: 01/24/2019] [Indexed: 01/22/2023]
Abstract
Long noncoding RNAs (lncRNAs), highly upregulated liver cancer (HULC), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), lncRNA-AF085935, and lncRNA-uc003wbd have been implicated in hepatocellular carcinoma (HCC). Single-nucleotide polymorphism (SNP) in HULC and MALAT1 are associated with HCC susceptibility. However, association between these SNPs and lncRNA-AF085935 and lncRNA-uc003wbd expression and their potential clinical value in differentiating HCC from both hepatitis B virus (HBV)-infected Egyptian patients and the healthy specimens have not been explored yet. In the present study, SNPs rs7763881 in HULC and rs619586 in MALAT1 were genotyped in 70 HBV-positive HCC, 70 HBV patients, and 70 healthy controls in Egyptian population and the level of serum lncRNA-AF085935 and lncRNA-uc003wbd of all the subjects was assayed by quantitative real-time polymerase chain reaction. HULC rs7763881 AC/CC genotype was significantly associated with decreased HCC risk. Similarly, AG/GG of MALAT1 rs619586 was associated with decreased HCC risk with a borderline significance. Serum lncRNA-AF085935 and lncRNA-uc003wbd levels were upregulated in HBV-positive HCC and HBV patients vs controls and discriminated these groups by receiver operating characteristic analysis. Patients carrying AC/CC genotype of rs7763881 and AG/GG of rs619586 had lower serum lncRNA-AF085935 and lncRNA-uc003wbd levels compared with AA genotype. In conclusion, genetic variants of lncRNA HULC and lncRNA MALAT1 are associated with the decreased susceptibility to HCC in HBV-persistent carriers and are correlated with serum lncRNA-AF085935 and lncRNAuc003wbd levels, two potential noninvasive diagnostic biomarkers for HCC.
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Affiliation(s)
- Tarek M K Motawi
- Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Shohda A El-Maraghy
- Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Dina Sabry
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Noha A Mehana
- Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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Heo MJ, Yun J, Kim SG. Role of non-coding RNAs in liver disease progression to hepatocellular carcinoma. Arch Pharm Res 2019; 42:48-62. [PMID: 30610616 DOI: 10.1007/s12272-018-01104-x] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Accepted: 12/23/2018] [Indexed: 12/17/2022]
Abstract
Hepatocellular carcinoma (HCC) is a tumor with poor prognosis and frequently aggressive. The development of HCC is associated with fibrosis and cirrhosis, which mainly results from nonalcoholic fatty liver disease, excessive alcohol consumption, and viral infections. Non-coding RNAs (ncRNAs) are RNAs transcribed from the genome, but are not translated into proteins. Recently, ncRNAs emerged as key contributors to tumor development and progression because of their abilities to regulate various targets and modulate cell proliferation, differentiation, apoptosis, and development. In this review, we summarize the frequently activated pathways in HCC and discuss the pathological implications of ncRNAs in the context of human liver disease progression, in particular HCC development and progression. This review aims to summarize the role of ncRNA dysregulation in the diseases and discuss the diagnostic and therapeutic potentials of ncRNAs.
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Affiliation(s)
- Mi Jeong Heo
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanakro, Seoul, 08826, South Korea
| | - Jessica Yun
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanakro, Seoul, 08826, South Korea
| | - Sang Geon Kim
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanakro, Seoul, 08826, South Korea.
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Diagnostic Value of lncRNAs as Biomarker in Hepatocellular Carcinoma: An Updated Meta-Analysis. Can J Gastroenterol Hepatol 2018; 2018:8410195. [PMID: 30410873 PMCID: PMC6205093 DOI: 10.1155/2018/8410195] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2018] [Revised: 07/29/2018] [Accepted: 09/14/2018] [Indexed: 02/08/2023] Open
Abstract
Some long noncoding RNAs (lncRNAs) display aberrantly high or low expression in hepatocellular carcinoma (HCC) and have the potential to serve as diagnostic biomarkers. Here, we accomplished a meta-analysis based on current studies to assess the diagnostic value of lncRNAs in HCC. Eligible literatures were systematically selected from PubMed, Web of Science, and Embase (up to January 20, 2018) according to defined inclusion and exclusion criteria. QUADAS scale was applied to the quality assessment of the included studies. Statistical analysis was performed through bivariate random-effects models based on R software. Publication bias was evaluated by funnel plot and Begg's and Egger's tests. 16 articles containing 2,268 cancer patients and 2,574 controls were selected for the final meta-analysis. Random effect model was used for the meta-analysis due to significant between-study heterogeneity. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were 0.87(0.838-0.897), 0.829(0.794-0.86), 23.085(20.575-25.901), 4.533(4.239-4.847), and 0.176(0.166-0.186), respectively. Summary receiver operating characteristic curve (SROC) was conducted to estimate the diagnostic accuracy of lncRNAs in HCC with the area under curve (AUC) of 0.915. Subgroups analysis showed that lncRNA profiling, sample size, specimen types, and ethnicity might be the sources of heterogeneity. No publication bias existed according to funnel plot symmetry and Begg's (P = 0.187) and Egger's (P = 0.477) tests. In conclusion, lncRNAs can serve as potential diagnostic biomarkers of HCC with high sensitivity and specificity. In addition, lncRNAs panel from serum and plasma has a relatively high diagnostic value for HCC patients from Asia.
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31
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Hu X, Jiang J, Xu Q, Ni C, Yang L, Huang D. A Systematic Review of Long Noncoding RNAs in Hepatocellular Carcinoma: Molecular Mechanism and Clinical Implications. BIOMED RESEARCH INTERNATIONAL 2018; 2018:8126208. [PMID: 30105249 PMCID: PMC6076971 DOI: 10.1155/2018/8126208] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Accepted: 04/10/2018] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) has the second highest mortality rate worldwide among all cancers. Previous studies have revealed the significant involvement of long noncoding RNAs (lncRNAs) in numerous human cancers including HCC. Both oncogenic and tumor repressive lncRNAs have been identified and implicated in the complex process of hepatocarcinogenesis. They can be further explored as prospective diagnostic, prognostic, and therapeutic markers for HCC. An in-depth understanding of lncRNAs' mechanism in HCC is therefore required to fully explore their potential role. In the current review, we will concentrate on the underlying function, molecular mechanisms, and potential clinical implications of lncRNA in HCC.
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Affiliation(s)
- Xiaoge Hu
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
| | - Jiahong Jiang
- Department of Second Clinical Medical College, Zhejiang Chinese Medicine University, Hangzhou, Zhejiang 310053, China
| | - Qiuran Xu
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
| | - Chao Ni
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
- Department of General Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
| | - Liu Yang
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
| | - Dongsheng Huang
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
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The expression and role of lncRNA AX800134 in hepatitis B virus-related hepatocellular carcinoma. Virus Genes 2018; 54:475-483. [DOI: 10.1007/s11262-018-1564-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Accepted: 04/27/2018] [Indexed: 02/07/2023]
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Cătană CS, Pichler M, Giannelli G, Mader RM, Berindan-Neagoe I. Non-coding RNAs, the Trojan horse in two-way communication between tumor and stroma in colorectal and hepatocellular carcinoma. Oncotarget 2018; 8:29519-29534. [PMID: 28392501 PMCID: PMC5438748 DOI: 10.18632/oncotarget.15706] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Accepted: 01/24/2017] [Indexed: 12/29/2022] Open
Abstract
In a continuous and mutual exchange of information, cancer cells are invariably exposed to microenvironment transformation. This continuous alteration of the genetic, molecular and cellular peritumoral stroma background has become as critical as the management of primary tumor progression events in cancer cells. The communication between stroma and tumor cells within the extracellular matrix is one of the triggers in colon and liver carcinogenesis. All non- codingRNAs including long non-coding RNAs, microRNAs and ultraconserved genes play a critical role in almost all cancers and are responsible for the modulation of the tumor microenvironment in several malignant processes such as initiation, progression and dissemination. This review details the involvement of non codingRNAs in the evolution of human colorectal carcinoma and hepatocellular carcinoma in relationship with the microenvironment. Recent research has shown that a considerable number of dysregulated non- codingRNAs could be valuable diagnostic and prognostic biomarkers in cancer. Therefore, more in-depth knowledge of the role non- codingRNAs play in stroma-tumor communication and of the complex regulatory mechanisms between ultraconserved genes and microRNAs supports the validation of future effective therapeutic targets in patients suffering from hepatocellular and colorectal carcinoma, two distinctive entities which share quite a lot common non-coding RNAs.
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Affiliation(s)
- Cristina- Sorina Cătană
- Department of Medical Biochemistry, ""Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Martin Pichler
- Department of Internal Medicine, Division of Oncology, Medical University of Graz, Graz, Austria
| | - Gianluigi Giannelli
- Department of Internal Medicine, Immunology and Infectious Diseases, Section of Internal Medicine, University of Bari Medical School, Bari, Italy
| | - Robert M Mader
- Department of Medicine I, Comprehensive Cancer Center of the Medical University of Vienna, Austria
| | - Ioana Berindan-Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Institute of Doctoral Studies, ""Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.,Department of Experimental Pathology, "Ion Chiricuta" Institute of Oncology, Cluj-Napoca, Romania.,Medfuture Research Center for Advanced Medicine, Cluj-Napoca, Romania
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Liu H, Li J, Koirala P, Ding X, Chen B, Wang Y, Wang Z, Wang C, Zhang X, Mo YY. Long non-coding RNAs as prognostic markers in human breast cancer. Oncotarget 2018; 7:20584-96. [PMID: 26942882 PMCID: PMC4991477 DOI: 10.18632/oncotarget.7828] [Citation(s) in RCA: 122] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2016] [Accepted: 02/18/2016] [Indexed: 02/02/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) have been recently shown to play an important role in gene regulation and normal cellular functions, and disease processes. However, despite the overwhelming number of lncRNAs identified to date, little is known about their role in cancer for vast majority of them. The present study aims to determine whether lncRNAs can serve as prognostic markers in human breast cancer. We interrogated the breast invasive carcinoma dataset of the Cancer Genome Atlas (TCGA) at the cBioPortal consisting of ~ 1,000 cases. Among 2,730 lncRNAs analyzed, 577 lncRNAs had alterations ranging from 1% to 32% frequency, which include mutations, alterations of copy number and RNA expression. We found that deregulation of 11 lncRNAs, primarily due to copy number alteration, is associated with poor overall survival. At RNA expression level, upregulation of 4 lncRNAs (LINC00657, LINC00346, LINC00654 and HCG11) was associated with poor overall survival. A third signature consists of 9 lncRNAs (LINC00705, LINC00310, LINC00704, LINC00574, FAM74A3, UMODL1-AS1, ARRDC1-AS1, HAR1A, and LINC00323) and their upregulation can predict recurrence. Finally, we selected LINC00657 to determine their role in breast cancer, and found that LINC00657 knockout significantly suppresses tumor cell growth and proliferation, suggesting that it plays an oncogenic role. Together, these results highlight the clinical significance of lncRNAs, and thus, these lncRNAs may serve as prognostic markers for breast cancer.
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Affiliation(s)
- Hairong Liu
- Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.,Department of Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China
| | - Juan Li
- Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.,Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shangdong Province, China
| | - Pratirodh Koirala
- Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.,Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS, USA
| | - Xianfeng Ding
- Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.,College of Life Science, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China
| | - Binghai Chen
- Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.,Department of Urology, Affiliated Hospital of Jiangsu University, Jiangsu, Zhenjiang, China
| | - Yiheng Wang
- School of Computing, University of Southern Mississippi, Hattiesburg, MS, USA
| | - Zheng Wang
- School of Computing, University of Southern Mississippi, Hattiesburg, MS, USA
| | - Chuanxin Wang
- Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shangdong Province, China
| | - Xu Zhang
- Center of Biostatistics and Bioinformatics, Department of Preventive Medicine, University of Mississippi Medical Center, Jackson, MS, USA
| | - Yin-Yuan Mo
- Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.,Department of Pharmacology/Toxicology, University of Mississippi Medical Center, Jackson, MS, USA
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35
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Zheng H, Li P, Kwok JG, Korrapati A, Li WT, Qu Y, Wang XQ, Kisseleva T, Wang-Rodriguez J, Ongkeko WM. Alcohol and hepatitis virus-dysregulated lncRNAs as potential biomarkers for hepatocellular carcinoma. Oncotarget 2017; 9:224-235. [PMID: 29416609 PMCID: PMC5787460 DOI: 10.18632/oncotarget.22921] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2017] [Accepted: 11/09/2017] [Indexed: 12/28/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths because of frequent late detection and poor therapeutic outcomes, necessitating the need to identify effective biomarkers for early diagnosis and new therapeutic targets for effective treatment. Long noncoding RNAs (lncRNAs) have emerged as promising molecular markers for diagnosis and treatment. Through analysis of patient samples from The Cancer Genome Atlas database, we identified putative lncRNAs dysregulated in HCC and by its risk factors, hepatitis infection and alcohol consumption. We identified 184 lncRNAs dysregulated in HCC tumors versus paired normal samples, 53 lncRNAs dysregulated in alcohol-drinking patients with hepatitis B, and 5, 456 lncRNAs dysregulated in patients with hepatitis infection. A panel of these candidate lncRNAs’ expressions correlated significantly with patient survival, clinical variables, and known genomic alteration in HCC. Two most significantly dysregulated lncRNAs in our computational analysis, lnc-CFP-1:1 and lnc-CD164L2-1:1, were validated in vitro to be dysregulated by alcohol. Our findings suggest that lncRNAs dysregulated by different etiologies of HCC serve as potential disease markers and can be further investigated to develop personalized prevention, diagnosis, and treatment strategies.
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Affiliation(s)
- Hao Zheng
- Department of Surgery, University of California, San Diego, La Jolla, California, USA
| | - Pinxue Li
- Department of Surgery, University of California, San Diego, La Jolla, California, USA
| | - James G Kwok
- Department of Surgery, University of California, San Diego, La Jolla, California, USA
| | - Avinaash Korrapati
- Department of Surgery, University of California, San Diego, La Jolla, California, USA
| | - Wei Tse Li
- Department of Surgery, University of California, San Diego, La Jolla, California, USA
| | - Yuanhao Qu
- Department of Surgery, University of California, San Diego, La Jolla, California, USA
| | - Xiao Qi Wang
- Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Tatiana Kisseleva
- Department of Surgery, University of California, San Diego, La Jolla, California, USA
| | - Jessica Wang-Rodriguez
- Veterans Administration Medical Center and Department of Pathology, University of California, San Diego, La Jolla, California, USA
| | - Weg M Ongkeko
- Department of Surgery, University of California, San Diego, La Jolla, California, USA
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Long noncoding RNAs in the initiation, progression, and metastasis of hepatocellular carcinoma. Noncoding RNA Res 2017; 2:129-136. [PMID: 30159431 PMCID: PMC6084840 DOI: 10.1016/j.ncrna.2017.11.001] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Revised: 11/27/2017] [Accepted: 11/27/2017] [Indexed: 12/19/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Despite awareness of risk factors for the development of HCC and advances in the diagnosis and clinical management of the disease, the molecular mechanisms underlying hepatocarcinogenesis remain poorly understood. Recent experimental studies provide strong evidence that long noncoding RNAs (lncRNAs), non-protein-coding transcripts with lengths >200 basepairs, contribute to the pathogenesis of numerous human diseases. Over the past decade, a role for lncRNAs in the initiation, progression, and metastasis of HCC has likewise emerged and developed into a highly active area of research. Although many lncRNAs appear to be dysregulated in HCC, extensive functional characterization has been performed on only a small proportion of these candidates to date. This review summarizes select lncRNAs that have been shown to wield functional relevance in the initiation, progression, or metastasis of HCC, focusing on the specific mechanisms by which lncRNA effects might be linked to clinical manifestations of the disease. In addition, an overview of circulating lncRNAs that have been identified as potential biomarkers for the diagnosis and prognosis of HCC is provided.
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Wang XJ, Jiang SC, Wei HX, Deng SQ, He C, Peng HJ. The Differential Expression and Possible Function of Long Noncoding RNAs in Liver Cells Infected by Dengue Virus. Am J Trop Med Hyg 2017; 97:1904-1912. [PMID: 29016307 DOI: 10.4269/ajtmh.17-0307] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The function of long noncoding RNAs (lncRNAs) in liver injury resulted by dengue virus (DENV) infection have not yet been explored. The differential expression profiles of lncRNAs (as well as mRNAs) in the L-02 liver cells infected by DENV1, DENV2, or uninfected were compared and analyzed after a high throughput RNA seq. The significantly up-regulated and down-regulated lncRNAs (or mRNAs) resulted by DENV infection were identified with a cutoff value at log2 (ratio) ≥ 1.5 and log2 (ratio) ≤ -1.5 (ratio = the reads of the lncRNAs or mRNAs from the infection groups divided by the reads from the control group). Several differentially expressed lncRNAs were verified with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Target gene analysis, pre-miRNA prediction, and the lncRNA-mRNA co-expression network construction were performed to predict the function of the differentially expressed lncRNAs. The differentially expressed lncRNAs were associated with biosynthesis, DNA/RNA related processes, inhibition of estrogen signaling pathway, sterol biosynthetic process, protein dimerization activity, vesicular fraction in DENV1 infection group; and with protein secretion, methyltransferase process, host cell cytoskeleton reorganization and the small GTPase Ras superfamily, inhibition of cell proliferation, induction of apoptosis in DENV2 infection. LncRNAs might be novel diagnostic markers and targets for further researches on dengue infection and liver injury resulted by dengue virus.
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Affiliation(s)
- Xiao-Jun Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Medical University, Dongguan, Guangdong, People's Republic of China.,Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Shi-Chen Jiang
- Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Hai-Xia Wei
- Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Sheng-Qun Deng
- Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Cheng He
- Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Hong-Juan Peng
- Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, and Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China
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Long Noncoding RNAs Act as Novel Biomarkers for Hepatocellular Carcinoma: Progress and Prospects. BIOMED RESEARCH INTERNATIONAL 2017; 2017:6049480. [PMID: 28835896 PMCID: PMC5557260 DOI: 10.1155/2017/6049480] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Revised: 06/20/2017] [Accepted: 07/04/2017] [Indexed: 12/15/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and confers a poor prognosis. Novel diagnostic or prognostic biomarkers and effective therapeutic targets for HCCs are urgently needed. Currently, dozens of long noncoding RNAs (lncRNAs) have been identified as playing critical roles in cancer development and progression. Advanced studies have shown that several well-known lncRNAs are dysregulated in HCC tissue as compared to adjacent noncancerous tissue. Furthermore, highly stable cell-free circulating nucleic acids (cfCNAs), including lncRNAs, aberrantly expressed in the plasma of HCC patients, have been detected. In this review, we focus on the most extensively investigated lncRNAs in HCC and discuss the potential of HCC-related lncRNAs as novel biomarkers for early diagnosis and prognosis.
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Bhan A, Soleimani M, Mandal SS. Long Noncoding RNA and Cancer: A New Paradigm. Cancer Res 2017; 77:3965-3981. [PMID: 28701486 PMCID: PMC8330958 DOI: 10.1158/0008-5472.can-16-2634] [Citation(s) in RCA: 2130] [Impact Index Per Article: 266.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Revised: 04/05/2017] [Accepted: 05/04/2017] [Indexed: 12/11/2022]
Abstract
In addition to mutations or aberrant expression in the protein-coding genes, mutations and misregulation of noncoding RNAs, in particular long noncoding RNAs (lncRNA), appear to play major roles in cancer. Genome-wide association studies of tumor samples have identified a large number of lncRNAs associated with various types of cancer. Alterations in lncRNA expression and their mutations promote tumorigenesis and metastasis. LncRNAs may exhibit tumor-suppressive and -promoting (oncogenic) functions. Because of their genome-wide expression patterns in a variety of tissues and their tissue-specific expression characteristics, lncRNAs hold strong promise as novel biomarkers and therapeutic targets for cancer. In this article, we have reviewed the emerging functions and association of lncRNAs in different types of cancer and discussed their potential implications in cancer diagnosis and therapy. Cancer Res; 77(15); 3965-81. ©2017 AACR.
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Affiliation(s)
- Arunoday Bhan
- Gene Regulation and Epigenetics Research Lab, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, Texas
| | - Milad Soleimani
- Gene Regulation and Epigenetics Research Lab, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, Texas
| | - Subhrangsu S Mandal
- Gene Regulation and Epigenetics Research Lab, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, Texas.
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Zheng C, Hao H, Chen L, Shao J. Long noncoding RNAs as novel serum biomarkers for the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis. Clin Transl Oncol 2017; 19:961-968. [PMID: 28188488 DOI: 10.1007/s12094-017-1626-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Accepted: 01/28/2017] [Indexed: 12/16/2022]
Abstract
PURPOSE Long noncoding RNAs (lncRNAs) are outstanding as novel cancer biomarkers with great prospects. Herein, we focused on summarizing the overall diagnostic evaluation of lncRNAs for hepatocellular carcinoma (HCC). METHODS Relevant literature was collected from the online databases. The Quality Assessment for Studies of Diagnostic Accuracy checklist was used to assess the quality of included studies. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were plotted using random-effects models. Summary receiver operating characteristic curve and the area under the curve (AUC) were used to estimate the overall test performance. Statistical analysis was performed by STATA 14.0 and Meta-DiSc 1.4 software. RESULTS Ten studies with a total of 820 HCC patients and 785 healthy controls were included. For overall lncRNAs, the pooled sensitivity, specificity, and DOR to predict HCC patients were 80% [95% confidence interval (CI) 77-82%], 79% (95% CI 76-81%), and 27.66 (95% CI 14.26-53.63), respectively, corresponding to an AUC of 0.91. CONCLUSIONS LncRNAs were a high diagnostic value for HCC and its expression could potentially be used as auxiliary biomarker in confirming HCC.
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Affiliation(s)
- C Zheng
- Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, 330000, China
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, 330000, China
| | - H Hao
- Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, 330000, China
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, 330000, China
| | - L Chen
- Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, 330000, China
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, 330000, China
| | - J Shao
- Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, 330000, China.
- Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, 330000, China.
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Deng Q, Chen S, Fu C, Jiang J, Zou M, Tan Y, Wang X, Xia F, Feng K, Ma K, Bie P. Long noncoding RNA expression profiles in sub-lethal heat-treated hepatoma carcinoma cells. World J Surg Oncol 2017; 15:136. [PMID: 28732507 PMCID: PMC5521104 DOI: 10.1186/s12957-017-1194-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Accepted: 06/22/2017] [Indexed: 02/06/2023] Open
Abstract
Background Sub-lethal heat treatment characterizes a transition zone of radiofrequency ablation (RFA) which explains hepatocellular carcinoma (HCC) residual cancer occurrence in this area after RFA treatment. The biochemistry of residual cancer cell recurrence is poorly understood, but long noncoding RNAs (lncRNAs) may have aberrant expression that is associated with diverse cancers. Thus, we measured lncRNA gene expression in sub-lethally heat-treated HCC cells using microarray. Method Differentially expressed lncRNA and mRNA were measured with an Agilent Human lncRNA + mRNA Array V4.0 (4 × 180 K format) containing 41,000 lncRNAs and 34,000 mRNAs. Bioinformatics analysis was used to assess differentially expressed lncRNA and mRNA. Seven lncRNA and seven mRNA were validated by qRT-PCR analysis in HCC cells. Results Genome-wide lncRNA and mRNA expression data in sub-lethal heat-treated SMMC-7721 HCC cells 558 lncRNA and 250 mRNA were significantly up-regulated and 224 lncRNA and 1031 mRNA down-regulated compared to normal cultured SMMC-7721 cells. We demonstrated for the first time that ENST00000570843.1, ENST00000567668.1, ENST00000582249.1, ENST00000450304.1, TCONS_00015544, ENST00000602478.1, TCONS_00001266 and ARC, IL12RB1, HSPA6 were upregulated, whereas STAT3, PRPSAP1, MCU, URB2 were down-regulated in sub-lethally heat-treated HCC cells. Conclusions lncRNA expression data in sub-lethally heat-treated HCC cells will provide important insights about lncRNAs’ contribution to HCC recurrence after RFA treatment. Electronic supplementary material The online version of this article (doi:10.1186/s12957-017-1194-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Qingsong Deng
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Shihan Chen
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Chunchuan Fu
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Jiayun Jiang
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Mengda Zou
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Yunhua Tan
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Xiaofei Wang
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Feng Xia
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Kai Feng
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
| | - Kuansheng Ma
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
| | - Ping Bie
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
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Hao QQ, Chen GY, Zhang JH, Sheng JH, Gao Y. Diagnostic value of long noncoding RNAs for hepatocellular carcinoma: A PRISMA-compliant meta-analysis. Medicine (Baltimore) 2017; 96:e7496. [PMID: 28700498 PMCID: PMC5515770 DOI: 10.1097/md.0000000000007496] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Increasing evidences have shown that long noncoding RNAs (lncRNAs) are involved in cancer diagnosis and prognosis. However, the overall diagnostic accuracy of lncRNAs for hepatocellular carcinoma (HCC) remains unclear. Herein, we perform a meta-analysis to assess diagnostic value of lncRNAs for HCC. METHODS The online PubMed, Cochrane, Web of Science, and Embase database were searched for eligible studies published until October 5, 2016. Study quality was evaluated with the Quality Assessment for Studies of Diagnostic Accuracy (QUADAS). All statistical analyses were conducted with Stata 12.0 and Meta-Disc 1.4. RESULTS We included 19 studies from 10 articles with 1454 patients with HCC and 1300 controls. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and AUC for lncRNAs in the diagnosis of HCC were 0.83 (95% confidence interval [CI]: 0.76-0.88), 0.80 (95% CI: 0.73-0.86), 4.2 (95% CI: 3.00-5.80), 0.21 (95% CI: 0.15-0.31), 20 (95% CI: 11-34), and 0.88 (95% CI: 0.85-0.91), respectively. Additionally, the diagnostic value of lncRNAs varied based on sex ratio of cases and characteristics of methods (specimen type and reference gen). CONCLUSION This meta-analysis suggests lncRNAs show a moderate diagnostic accuracy for HCC. However, prospective studies are required to confirm its diagnostic value.
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Saitta C, Raffa G, Alibrandi A, Brancatelli S, Lombardo D, Tripodi G, Raimondo G, Pollicino T. PIVKA-II is a useful tool for diagnostic characterization of ultrasound-detected liver nodules in cirrhotic patients. Medicine (Baltimore) 2017; 96:e7266. [PMID: 28658121 PMCID: PMC5500043 DOI: 10.1097/md.0000000000007266] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Protein induced by vitamin K absence-II (PIVKA-II) is a potential screening marker for hepatocellular carcinoma (HCC). Limited data are available about its utility in discriminating neoplastic from regenerative nodules at ultrasonography (US) evaluation in cirrhotic patients. Aim of this study was to investigate the diagnostic utility of PIVKA-II in cases showing liver nodules of uncertain diagnosis at US.Ninety cirrhotics with US evidence of liver nodule(s) were enrolled. All patients underwent blood sampling within 1 week of US and were thereafter followed up. HCC was confirmed in 40/90 cases, and in all cases it was in a very early/early stage. All sera were tested for PIVKA-II and alpha-fetoprotein (AFP) at the end of follow-up. PIVKA-II at a cut off of 60 mAU/mL was significantly associated with HCC at both univariate and multivariate analysis (P = .016 and P = .032, respectively). AFP at a cut off of 6.5 ng/mL was not associated with HCC at univariate analysis (P = .246). ROC curves showed that PIVKA-II had 60% sensitivity, 88% specificity, 80% positive predictive value (PPV), and 73% negative predictive value (NPV), whereas AFP had 67% sensitivity, 68% specificity, 63% PPV, and 72% NPV. AUROC curves showed that the combination of both biomarkers increased the diagnostic accuracy for HCC (AUC 0.76; sensitivity 70%, specificity 94%, PPV 91%, and NPV 79%).In conclusion, PIVKA-II is a useful tool for the diagnostic definition of US-detected liver nodules in cirrhotic patients, and it provides high diagnostic accuracy for HCC when combined with AFP.
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Affiliation(s)
- Carlo Saitta
- Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina
| | - Giuseppina Raffa
- Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina
- Department of Clinical and Experimental Medicine
| | | | - Santa Brancatelli
- Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina
- Department of Clinical and Experimental Medicine
| | | | | | - Giovanni Raimondo
- Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina
- Department of Clinical and Experimental Medicine
| | - Teresa Pollicino
- Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina
- Department of Human Pathology, University of Messina, Messina, Italy
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Liu W, Ding C. Roles of LncRNAs in Viral Infections. Front Cell Infect Microbiol 2017; 7:205. [PMID: 28603696 PMCID: PMC5445353 DOI: 10.3389/fcimb.2017.00205] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Accepted: 05/08/2017] [Indexed: 12/12/2022] Open
Abstract
Many proteins and signaling pathways participate in anti-viral host responses. Long non-coding RNAs (lncRNAs), a subset of non-coding RNAs greater than 200 nucleotides in length, have been recently described as critical regulators in viral infections. Accumulating research indicates that lncRNAs are important in the development and progression of infectious diseases. LncRNAs are not only involved in anti-viral responses, but in many different virus-host interactions, some of which may be beneficial to the virus. Here we review the current knowledge regarding host and viral lncRNAs and their roles in viral infections. In addition, the potential of using lncRNAs as diagnostic biomarkers is discussed.
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Affiliation(s)
- Weiwei Liu
- Avian infectious Department, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural ScienceShanghai, China
| | - Chan Ding
- Avian infectious Department, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural ScienceShanghai, China
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Deng X, Zhao XF, Liang XQ, Chen R, Pan YF, Liang J. Linc00152 promotes cancer progression in hepatitis B virus-associated hepatocellular carcinoma. Biomed Pharmacother 2017; 90:100-108. [PMID: 28343069 DOI: 10.1016/j.biopha.2017.03.031] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2017] [Revised: 02/26/2017] [Accepted: 03/10/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The X protein (HBx) plays as a key role in hepatocarcinogenesis associated with hepatitis B virus (HBV) infections. The study aimed to figure out the role of Linc00152 in hepatocellular carcinoma (HCC) and the association between the expression levels of Linc00152 and HBx. METHODS QRT-PCR assays were applied to analyzed the expression levels of Linc00152 and HBx. Kaplan-Meier survival curve was performed to identify the association between LINC00152 and the over survival time (OS) in HCC patients. Cell growth and invasion ability was evaluated by CCK8 cell proliferation and transwell invasion assays. Western-blot analysis was detected the protein expression. RNA immunoprecipitation (RIP), RNA-pull down and chromatin Immunoprecipitation (ChIP) assays was also been carried out. RESULTS We demonstrated that LINC00152 expression in hepatocellular carcinoma (HCC) patients was significantly higher compared with adjacent non-tumour tissues and positively correlated with tumor size, HBV infection (HBsAg) and tumor number. Patient with hepatitis B virus (HBV) infection HCC was higher expression than that without HBV. Furthermore, the expression levels of Linc00152 were positively correlated with HBx expression in HCC tissues and higher Linc00152 expression levels were correlated with poor prognosis of HCC patients. In vitro, Linc00152 was up-regulated in Huh-7 and SM7721 cells after overexpression of HBx and down-regulated after silencing HBx. Furthermore, silencing Linc00152 suppressed the cell proliferation and invasion. Moreover, we found that Linc00152 inhibited the E-cadherin expression via interacting with EZH2 and promoted the Epithelial-mesenchymal transition (EMT) phenomenon in HCC cells. CONCLUSIONS These results suggested that HBx enhanced LINC00152 expression and inhibition of LINC00152 could provide a therapeutic target for HCC.
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Affiliation(s)
- Xin Deng
- Infectious Diseases Laboratory, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Xiao Fang Zhao
- Infectious Diseases Laboratory, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Xing Qiu Liang
- Infectious Diseases Laboratory, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Ran Chen
- Department of Gastroenterology, the first affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Yi Feng Pan
- Hepatobiliary Intestine Research Center, XiangYa School of Medicine, Central South University, Changsha, China
| | - Jian Liang
- Infectious Diseases Laboratory, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
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Shi L, Peng F, Tao Y, Fan X, Li N. Roles of long noncoding RNAs in hepatocellular carcinoma. Virus Res 2016; 223:131-9. [PMID: 27374059 DOI: 10.1016/j.virusres.2016.06.008] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 05/19/2016] [Accepted: 06/15/2016] [Indexed: 12/11/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high prevalence and lethality. Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection are the major risk factors for HCC. Long noncoding RNAs (lncRNAs) are involved in diverse biological processes, and aberrant lncRNA expression is relevant to many human diseases including HCC. Although many researches on HCC have been reported and lncRNAs roles in carcinogenesis have been highlighted recently, reports on roles of lncRNAs in HBV/HCV-induced HCC are limited. In this review, we concentrate on recent progress regarding the functional roles of lncRNAs in HCC and HBV/HCV-related HCC.
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Affiliation(s)
- Linxi Shi
- Department of Blood Transfusion, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan Province 410008, China
| | - Fang Peng
- Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China
| | - Yongguang Tao
- Cancer Research Institute, Central South University, 87 Xiangya Road, Changsha, Hunan 410078, China
| | - Xuegong Fan
- Hunan Key Laboratory of Viral Hepatitis,Xiangya Hospital, Central South University, Hunan Province, 87 Xiangya Road, Changsha 410008, China.
| | - Ning Li
- Department of Blood Transfusion, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan Province 410008, China.
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