|
1
|
Wang Z, Xie C, Chen X. Diagnostic and therapeutic role of non-coding RNAs regulating programmed cell death in melanoma. Front Oncol 2024; 14:1476684. [PMID: 39777348 PMCID: PMC11703721 DOI: 10.3389/fonc.2024.1476684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025] Open
Abstract
lncRNAs (long non-coding RNAs) are heterogeneous RNA molecules that modulate various cellular processes, such as proliferation, differentiation, migration, invasion, and apoptosis, via different mechanisms. An increasing amount of research indicates that abnormal expression of lncRNA influences the development of drug resistance as well as the genesis and advancement of cancer, including melanoma. Furthermore, they are attractive biomarkers for non-invasive cancer diagnostics due to their strongly modulated expression and improved tissue and disease specificity. This review offers a succinct overview of the present understanding concerning the potential diagnostic biomarker potential of lncRNAs in melanoma. Cell death occurs frequently during growth and throughout life and is an active, organized, and genetically determined process. It is essential for the regulation of homeostasis. Controlled cell death and non-programmed cell death are both forms of cell death. The most prevalent forms of regulatory cell death are pyroptosis, ferroptosis, autophagy, necroptosis, necrosis, and apoptosis. Ferroptosis, pyroptosis, and autophagy are less common forms of cell death compared to necrosis, apoptosis, and necroptosis. ncRNAs are regulatory RNA molecules that are not involved in encoding proteins. They primarily consist of circular RNAs (circ RNAs), lncRNAs, and microRNAs (miRNAs). Moreover, non-coding RNAs have the ability to modulate tumor cell autophagy, pyroptosis, and ferroptosis at the transcriptional or post-transcriptional stage, as well as function as oncogenes and tumor suppressor genes, which can have considerable effects on the incidence and growth of tumors. This review concentrated on the recent advancements in the research of the diagnostic and therapeutic functions of ncRNAs in the regulation of programmed cell death in melanoma.
Collapse
Affiliation(s)
- Zixu Wang
- Office for Doctoral Studies, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Cong Xie
- Office for Doctoral Studies, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Xiao Chen
- Office for Postgraduate Student Studies, Kunming Medical University, Kunming, China
| |
Collapse
|
|
2
|
Tsai CC, Wang CY, Chang HH, Chang PTS, Chang CH, Chu TY, Hsu PC, Kuo CY. Diagnostics and Therapy for Malignant Tumors. Biomedicines 2024; 12:2659. [PMID: 39767566 PMCID: PMC11726849 DOI: 10.3390/biomedicines12122659] [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: 10/31/2024] [Revised: 11/20/2024] [Accepted: 11/20/2024] [Indexed: 01/03/2025] Open
Abstract
Malignant tumors remain one of the most significant global health challenges and contribute to high mortality rates across various cancer types. The complex nature of these tumors requires multifaceted diagnostic and therapeutic approaches. This review explores current advancements in diagnostic methods, including molecular imaging, biomarkers, and liquid biopsies. It also delves into the evolution of therapeutic strategies, including surgery, chemotherapy, radiation therapy, and novel targeted therapies such as immunotherapy and gene therapy. Although significant progress has been made in the understanding of cancer biology, the future of oncology lies in the integration of precision medicine, improved diagnostic tools, and personalized therapeutic approaches that address tumor heterogeneity. This review aims to provide a comprehensive overview of the current state of cancer diagnostics and treatments while highlighting emerging trends and challenges that lie ahead.
Collapse
Affiliation(s)
- Chung-Che Tsai
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan; (C.-C.T.); (C.-H.C.); (T.Y.C.)
| | - Chun-Yu Wang
- Department of Dentistry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan;
| | - Hsu-Hung Chang
- Division of Nephrology, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei City 221, Taiwan;
| | | | - Chuan-Hsin Chang
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan; (C.-C.T.); (C.-H.C.); (T.Y.C.)
| | - Tin Yi Chu
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan; (C.-C.T.); (C.-H.C.); (T.Y.C.)
| | - Po-Chih Hsu
- Department of Dentistry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan;
- Institute of Oral Medicine and Materials, College of Medicine, Tzu Chi University, Hualien 970, Taiwan
| | - Chan-Yen Kuo
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan; (C.-C.T.); (C.-H.C.); (T.Y.C.)
| |
Collapse
|
|
3
|
Shetti D, Mallela VR, Ye W, Sharif M, Ambrozkiewicz F, Trailin A, Liška V, Hemminki K. Emerging role of circulating cell-free RNA as a non-invasive biomarker for hepatocellular carcinoma. Crit Rev Oncol Hematol 2024; 200:104391. [PMID: 38795877 DOI: 10.1016/j.critrevonc.2024.104391] [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: 03/14/2024] [Revised: 04/30/2024] [Accepted: 05/19/2024] [Indexed: 05/28/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a severe neoplastic disease associated with high morbidity and mortality rates. HCC is often detected at advanced stages leading to ineffective curative treatments. Recently, liquid biopsy has emerged as a non-invasive method to identify highly specific HCC biomarkers in bodily fluids such as blood, serum, urine, and saliva. Circulating cell-free nucleic acids (cfNAs), particularly cell-free DNA (cfDNA) and cell-free RNA (cfRNA), have become promising candidates for biomarkers in liquid biopsy applications. While cfDNA presented significant challenges, researchers have turned their attention to cfRNA, which can be efficiently identified through various methods and is considered a potential biomarker for cancer diagnosis and prognosis. This review primarily focuses on studies related to detecting various cfRNA in body fluids as biomarkers. The aim is to provide a summary of available information to assist researchers in their investigations and the development of new diagnostic and prognostic tools.
Collapse
Affiliation(s)
- Dattatrya Shetti
- Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, Pilsen 323 00, Czech Republic.
| | - Venkata Ramana Mallela
- Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, Pilsen 323 00, Czech Republic
| | - Wenjing Ye
- Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, Pilsen 323 00, Czech Republic
| | - Mahyar Sharif
- Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University,Alej Svobody 1665/76, Pilsen 323 00, Czech Republic
| | - Filip Ambrozkiewicz
- Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, Pilsen 323 00, Czech Republic
| | - Andriy Trailin
- Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, Pilsen 323 00, Czech Republic
| | - Václav Liška
- Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, Pilsen 323 00, Czech Republic; Department of Surgery, University Hospital in Pilsen and Faculty of Medicine in Pilsen, Charles University, Alej Svobody 80, Pilsen 323 00, Czech Republic
| | - Kari Hemminki
- Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, Pilsen 323 00, Czech Republic; Department of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, Germany
| |
Collapse
|
|
4
|
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.
Collapse
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
| |
Collapse
|
|
5
|
Yu P, Ye J, Zhao S, Cai Y. lncRNAs are potential prognostic markers in patients with nasopharyngeal carcinoma in China: A systematic review and meta‑analysis. Mol Clin Oncol 2024; 20:11. [PMID: 38213659 PMCID: PMC10777463 DOI: 10.3892/mco.2023.2709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 12/04/2023] [Indexed: 01/13/2024] Open
Abstract
The present study aimed to investigate the association between the expression profiles of long non-coding RNAs (lncRNAs) and the clinical characteristics or prognosis of patients with nasopharyngeal carcinoma (NPC). The findings presented in the present review may provide novel strategies for the prevention and treatment of NPC. For the analyses, medical databases, including PubMed, Web of Science and Cochrane library were searched using specific search terms, search strategies and screening strategies. Endnote X9 document management software was then employed to extract documents from January, 2010 to May, 2023. Data were extracted following the prescribed standards. Review Manager 5.4 and STATA 12.0 data analysis software were used for data analysis. A total of 490 publications were analyzed for inclusion. In total, 29 publications, composed of 24 studies with upregulated lncRNAs and 5 studies with downregulated lncRNAs, were included in the final analysis. The analysis revealed that the upregulation of lncRNAs was significantly associated with T stage, N stage and clinical stage, as well as with the overall survival (OS) and disease-free survival (DFS) of patients with NPC (P<0.05). However, there was no significant association between the upregulated lncRNAs and sex, M stage or relapse-free survival (RFS) (P>0.05). On the other hand, the suppression of lncRNA expression was significantly associated with N stage, M stage, clinical stage and the OS of patients with NPC (P<0.05), but not with T stage and RFS (P>0.05). Taken together, the present review demonstrates that the up- and downregulation of different lncRNAs was associated with an advanced clinical stage and a shorter OS of patients with NPC. Therefore, lncRNAs may serve as potential prognostic factors in NPC.
Collapse
Affiliation(s)
- Peng Yu
- School of Clinical Medicine, Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region 541199, P.R. China
| | - Jiemei Ye
- Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi Zhuang Autonomous Region 543002, P.R. China
| | - Shujian Zhao
- Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi Zhuang Autonomous Region 543002, P.R. China
| | - Yonglin Cai
- Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi Zhuang Autonomous Region 543002, P.R. China
- Department of Preventive Medicine, Wuzhou Cancer Center, Wuzhou, Guangxi Zhuang Autonomous Region 543002, P.R. China
| |
Collapse
|
|
6
|
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.
Collapse
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
Collapse
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.)
| |
Collapse
|
|
7
|
Masoud A, Mohamadynejad P. Identification of lncRNA PCAT19 as potential novel biomarker for colorectal cancer. Gene 2024; 891:147828. [PMID: 37748628 DOI: 10.1016/j.gene.2023.147828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Revised: 09/15/2023] [Accepted: 09/22/2023] [Indexed: 09/27/2023]
Abstract
Long non-coding RNAs have been implicated in biological processes, and are dysregulated in types of cancer. Studies have shown that PCAT19 and CKMT2-AS1 lncRNAs promote tumor growth, invasion, and metastasis by regulating signaling pathways and modulating the gene expression. This study investigated the expression levels of lncRNAs PCAT19 and CKMT2-AS1 in colorectal tumors and normal tissues. First, Using GEPIA2 database, we compared the expression level of target lncRNAs between primary colon adenocarcinoma tumor and normal tissues. Then, the expression levels of lncRNAs PCAT19 and CKMT2-AS1 were detected in 35 colorectal tumors and paired adjacent tissues using qRT-PCR. A receiver operating characteristic (ROC) curve was used to evaluate the value of these lncRNAs as biomarkers. Statistical analysis based on GEPIA2 showed that both lncRNAs PCAT19 and CKMT2-AS1 were significantly decreased in colon adenocarcinoma compared to the normal group (P < 0.001). Experimental analysis showed that the expression level of lncRNA PCAT19 was decreased in colorectal tumors (p < 0.0001) compared to normal tissues. While the expression level of lncRNA CKMT2-AS1 did not change in tumor tissues, it decreased in non-metastatic tumors compared to normal tissues (p = 0.04). The significantly downregulation of lncRNA PCAT19 expression in both metastatic and non-metastatic colorectal tumors compared to normal tissue suggests that PCAT19 may play a role in the carcinogenesis and progression of colorectal cancer and may provide potential therapeutic targets for colorectal cancer. Based on the results of ROC curve analysis, lncRNA PCAT19 may also serves as a novel potential good biomarker in diagnosis colorectal cancer (AUC = 0.94, p < 0.0001) but no significant was found for lncRNA CKMT2-AS1 (p > 0.05).
Collapse
Affiliation(s)
- Atousa Masoud
- Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| | - Parisa Mohamadynejad
- Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
| |
Collapse
|
|
8
|
Tsoneva DK, Ivanov MN, Vinciguerra M. Liquid Liver Biopsy for Disease Diagnosis and Prognosis. J Clin Transl Hepatol 2023; 11:1520-1541. [PMID: 38161500 PMCID: PMC10752811 DOI: 10.14218/jcth.2023.00040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 05/24/2023] [Accepted: 06/07/2023] [Indexed: 01/03/2024] Open
Abstract
Liver diseases are a major burden worldwide, the scope of which is expected to further grow in the upcoming years. Clinically relevant liver dysfunction-related blood markers such as alanine aminotransferase and aspartate aminotransferase have limited accuracy. Nowadays, liver biopsy remains the gold standard for several liver-related pathologies, posing a risk of complication due to its invasive nature. Liquid biopsy is a minimally invasive approach, which has shown substantial potential in the diagnosis, prognosis, and monitoring of liver diseases by detecting disease-associated particles such as proteins and RNA molecules in biological fluids. Histones are the core components of the nucleosomes, regulating essential cellular processes, including gene expression and DNA repair. Following cell death or activation of immune cells, histones are released in the extracellular space and can be detected in circulation. Histones are stable in circulation, have a long half-life, and retain their post-translational modifications. Here, we provide an overview of the current research on histone-mediated liquid biopsy methods for liver diseases, with a focus on the most common detection methods.
Collapse
Affiliation(s)
- Desislava K. Tsoneva
- Department of Medical Genetics, Medical University of Varna, Varna, Bulgaria
- Department of Stem Cell Biology and Transplantology, Research Institute, Medical University of Varna, Varna, Bulgaria
| | - Martin N. Ivanov
- Department of Stem Cell Biology and Transplantology, Research Institute, Medical University of Varna, Varna, Bulgaria
- Department of Anatomy and Cell Biology, Research Institute, Medical University of Varna, Varna, Bulgaria
| | - Manlio Vinciguerra
- Department of Stem Cell Biology and Transplantology, Research Institute, Medical University of Varna, Varna, Bulgaria
- Faculty of Health, Liverpool John Moores University, Liverpool, United Kingdom
| |
Collapse
|
|
9
|
Hamdy SM, Ali MS, Abd El-Hmid RG, Abdelghaffar NK, Abdelaleem OO. Role of Long non Coding RNAs, NEAT1 and Lnc-DC Expression in Pediatric Immune Thrombocytopenic Purpura. Rep Biochem Mol Biol 2023; 11:635-643. [PMID: 37131890 PMCID: PMC10149135 DOI: 10.52547/rbmb.11.4.635] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 11/10/2022] [Indexed: 05/04/2023]
Abstract
Background Pediatric immune thrombocytopenic purpura (ITP) is an autoimmune disease; whose etiology is unknown. lncRNAs are regulators of numerous actions, which participate in the development of autoimmune diseases. We evaluated the expression ofNEAT1 and Lnc-RNA in dendritic cell (Lnc-DC) in pediatric ITP. Methods Sixty ITP patients and 60 healthy subjects were enrolled in the present study; Real-time PCR was performed to assess the expression levels of NEAT1 and Lnc-DC in sera of children with ITP as well as healthy children. Results Both lncRNAs, NEAT1 and Lnc-DC were significantly upregulated in ITP patients in comparison to controls (p <0.0001 and P= 0.001 respectively). Furthermore, significant upregulation of the expression levels of NEAT1 and Lnc-DC were observed in the non-chronic compared with chronic ITP patients. Also, there was significant negative correlation between each of NEAT1 and Lnc-DC and platelet counts before treatment (r= -0.38; P= 0.003 and r= -0.461; P< 0.0001, respectively). Conclusions serum lncRNAs, NEAT1 and Lnc-DC could be used as potential biomarkers in differentiating childhood ITP patients and healthy controls in addition to differentiating non-chronic from chronic ITP which may provide a theoretical basis for the mechanism and treatment of immune thrombocytopenia.
Collapse
Affiliation(s)
- Soha Mohamed Hamdy
- Departments of Chemistry, Faculty of Science, Fayoum University, Fayoum, Egypt.
| | - Marwa Saad Ali
- Departments of Chemistry, Faculty of Science, Fayoum University, Fayoum, Egypt.
| | | | | | - Omayma Owees Abdelaleem
- Departments of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Fayoum University, Egypt.
- Corresponding author: Omayma Owees Abdelaleem; Tel: +01 049491030; E-mail:
| |
Collapse
|
|
10
|
Long Non-Coding RNAs Expressed in the Peanut Allergy for Understanding the Pathophysiology of Peanut Allergy Rat Model. Foods 2022; 11:foods11233760. [PMID: 36496569 PMCID: PMC9740276 DOI: 10.3390/foods11233760] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/11/2022] [Accepted: 11/18/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Peanut allergy (PA) has become a clinical and public health problem, which is mainly regulated by genetics, immune responses, and environmental factors. Diagnosis and treatment for PA have always remained huge challenges due to its multiple triggers. Studies have shown that long non-coding RNAs (lncRNAs) play a critical role in the development of allergic diseases. METHOD AND RESULTS In the current study, we examined the plasma lncRNA expression profiles of peanut allergy Brown Norway rats and healthy controls and 496 differently expressed lncRNAs were identified, including 411 up-regulated genes and 85 down-regulated genes. We screened 8 lncRNAs based on the candidate principle and the candidates were verified in individual samples by quantitative real-time PCR. Then, the four lncRNA-based diagnostic model was established by least absolute shrinkage and selection operator (LASSO) and logistic regression, which was proved by area under the receiver operating characteristic curve (AUC). CONCLUSIONS In summary, we assessed the correlation between lncRNA expression levels and the diagnosis of peanut allergy, which may perform a vital role in guiding the management of peanut allergy.
Collapse
|
|
11
|
Wang T, Zhou Z, Wang X, You L, Li W, Zheng C, Zhang J, Wang L, Kong X, Gao Y, Sun X. Comprehensive analysis of nine m7G-related lncRNAs as prognosis factors in tumor immune microenvironment of hepatocellular carcinoma and experimental validation. Front Genet 2022; 13:929035. [PMID: 36081998 PMCID: PMC9445240 DOI: 10.3389/fgene.2022.929035] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 07/18/2022] [Indexed: 12/24/2022] Open
Abstract
Background: Hepatocellular carcinoma (HCC) remains the most prevalent gastrointestinal malignancy worldwide, with robust drug resistance to therapy. N7-methylguanosine (m7G) mRNA modification has been significantly related to massive human diseases. Considering the effect of m7G-modified long non-coding RNAs (lncRNAs) in HCC progression is unknown, the study aims at investigating a prognostic signature to improve clinical outcomes for patients with HCC.Methods: Two independent databases (TCGA and ICGC) were used to analyze RNAseq data of HCC patients. First, co-expression analysis was applied to obtain the m7G-related lncRNAs. Moreover, consensus clustering analysis was employed to divide HCC patients into clusters. Then, using least absolute shrinkage and selection operator-Cox regression analysis, the m7G-related lncRNA prognostic signature (m7G-LPS) was first tested in the training set and then confirmed in both the testing and ICGC sets. The expression levels of the nine lncRNAs were further confirmed via real-time PCR in cell lines, principal component analysis, and receiver operating characteristic curve. The m7G-LPS could divide HCC patients into two different risk groups with the optimal risk score. Then, Kaplan–Meier curves, tumor mutation burden (TMB), therapeutic effects of chemotherapy agents, and expressions of immune checkpoints were performed to further enhance the availability of immunotherapeutic treatments for HCC patients.Results: A total of 1465 lncRNAs associated with the m7G genes were finally selected from the TCGA database, and through the univariate Cox regression, the expression levels of 22 m7G-related lncRNAs were concerning HCC patients’ overall survival (OS). Then, the whole patients were grouped into two subgroups, and the OS in Cluster 1 was longer than that of patients in Cluster 2. Furthermore, nine prognostic m7G-related lncRNAs were identified to conduct the m7G-LPS, which were further verified. A prognostic nomogram combined age, gender, HCC grade, stage, and m7G-LPS showed strong reliability and accuracy in predicting OS in HCC patients. Finally, immune checkpoint expression, TMB, and several chemotherapy agents were remarkably associated with risk scores. More importantly, the OS of the TMB-high patients was the worst among the four groups.Conclusion: The prognostic model we established was validated by abundant algorithms, which provided a new perspective on HCC tumorigenesis and thus improved individualized treatments for patients.
Collapse
Affiliation(s)
- Tao Wang
- Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhijia Zhou
- Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xuan Wang
- Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Liping You
- Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wenxuan Li
- Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Chao Zheng
- Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jinghao Zhang
- Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lingtai Wang
- Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaoni Kong
- Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- *Correspondence: Xiaoni Kong, ; Yueqiu Gao, ; Xuehua Sun,
| | - Yueqiu Gao
- Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- *Correspondence: Xiaoni Kong, ; Yueqiu Gao, ; Xuehua Sun,
| | - Xuehua Sun
- Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- *Correspondence: Xiaoni Kong, ; Yueqiu Gao, ; Xuehua Sun,
| |
Collapse
|
|
12
|
Ahmad E, Ali A, Nimisha, Kumar Sharma A, Apurva, Kumar A, Dar GM, Sumayya Abdul Sattar R, Verma R, Mahajan B, Singh Saluja S. Molecular markers in cancer. Clin Chim Acta 2022; 532:95-114. [DOI: https:/doi.org/10.1016/j.cca.2022.05.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/28/2023]
|
|
13
|
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).
Collapse
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.
| |
Collapse
|
|
14
|
Ahmad E, Ali A, Nimisha, Kumar Sharma A, Apurva, Kumar A, Mehdi G, Sumayya Abdul Sattar R, Verma R, Mahajan B, Singh Saluja S. Molecular markers in cancer. Clin Chim Acta 2022; 532:95-114. [DOI: 10.1016/j.cca.2022.05.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 05/31/2022] [Accepted: 05/31/2022] [Indexed: 12/01/2022]
|
|
15
|
Braghini MR, Lo Re O, Romito I, Fernandez-Barrena MG, Barbaro B, Pomella S, Rota R, Vinciguerra M, Avila MA, Alisi A. Epigenetic remodelling in human hepatocellular carcinoma. J Exp Clin Cancer Res 2022; 41:107. [PMID: 35331312 PMCID: PMC8943959 DOI: 10.1186/s13046-022-02297-2] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 02/19/2022] [Indexed: 04/13/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, being the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related death. As other heterogeneous solid tumours, HCC results from a unique synergistic combination of genetic alterations mixed with epigenetic modifications.In HCC the patterns and frequencies of somatic variations change depending on the nearby chromatin. On the other hand, epigenetic alterations often induce genomic instability prone to mutations. Epigenetics refers to heritable states of gene expression without alteration to the DNA sequence itself and, unlike genetic changes, the epigenetic modifications are reversible and affect gene expression more extensively than genetic changes. Thus, studies of epigenetic regulation and the involved molecular machinery are greatly contributing to the understanding of the mechanisms that underline HCC onset and heterogeneity. Moreover, this knowledge may help to identify biomarkers for HCC diagnosis and prognosis, as well as future new targets for more efficacious therapeutic approaches.In this comprehensive review we will discuss the state-of-the-art knowledge about the epigenetic landscape in hepatocarcinogenesis, including evidence on the diagnostic and prognostic role of non-coding RNAs, modifications occurring at the chromatin level, and their role in the era of precision medicine.Apart from other better-known risk factors that predispose to the development of HCC, characterization of the epigenetic remodelling that occurs during hepatocarcinogenesis could open the way to the identification of personalized biomarkers. It may also enable a more accurate diagnosis and stratification of patients, and the discovery of new targets for more efficient therapeutic approaches.
Collapse
Affiliation(s)
- Maria Rita Braghini
- Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital, IRCCS, Viale S. Paolo, 15, 00146, Rome, Italy
| | - Oriana Lo Re
- Department of Translational Stem Cell Biology, Research Institute of the Medical University of Varna, Varna, Bulgaria
| | - Ilaria Romito
- Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital, IRCCS, Viale S. Paolo, 15, 00146, Rome, Italy
| | - Maite G Fernandez-Barrena
- Hepatology Program, CIMA, University of Navarra, Pamplona, Spain
- Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
| | - Barbara Barbaro
- Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital, IRCCS, Viale S. Paolo, 15, 00146, Rome, Italy
| | - Silvia Pomella
- Department of Paediatric Haematology/Oncology and Cellular and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Rossella Rota
- Department of Paediatric Haematology/Oncology and Cellular and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Manlio Vinciguerra
- Department of Translational Stem Cell Biology, Research Institute of the Medical University of Varna, Varna, Bulgaria
| | - Matias A Avila
- Hepatology Program, CIMA, University of Navarra, Pamplona, Spain
- Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
| | - Anna Alisi
- Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital, IRCCS, Viale S. Paolo, 15, 00146, Rome, Italy.
| |
Collapse
|
|
16
|
Li D, Fan X, Li Y, Yang J, Lin H. The paradoxical functions of long noncoding RNAs in hepatocellular carcinoma: Implications in therapeutic opportunities and precision medicine. Genes Dis 2022; 9:358-369. [PMID: 35224152 PMCID: PMC8843871 DOI: 10.1016/j.gendis.2020.11.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 10/22/2020] [Accepted: 11/24/2020] [Indexed: 11/20/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is among the most aggressive and lethal diseases with poor prognosis, worldwide. However, the mechanisms underlying HCC have not been comprehensively elucidated. With the recent application of high-throughput sequencing techniques, a diverse catalogue of differentially expressed long non-coding RNAs (lncRNA) in cancer have been shown to participate in HCC. Rather than being "transcriptional noise," they are emerging as important regulators of many biological processes, including chromatin remodelling, transcription, alternative splicing, translational and post-translational modification. Moreover, lncRNAs have dual effects in the development and progression of HCC, including oncogenic and tumour-suppressive roles. Collectively, recently data point to lncRNAs as novel diagnostic and prognostic biomarkers with satisfactory sensitivity and specificity, as well as being therapeutic targets for HCC patients. In this review, we highlight recent progress of the molecular patterns of lncRNAs and discuss their potential clinical application in human HCC.
Collapse
Affiliation(s)
- Duguang Li
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
- Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
| | - Xiaoxiao Fan
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
- Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
| | - Yirun Li
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
- Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
| | - Jing Yang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
- Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
| | - Hui Lin
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
- Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
| |
Collapse
|
|
17
|
Wang W, Deng Z, Jin Z, Wu G, Wang J, Zhu H, Xu B, Wen Z, Guo Y. Bioinformatics analysis and experimental verification of five metabolism-related lncRNAs as prognostic models for hepatocellular carcinoma. Medicine (Baltimore) 2022; 101:e28694. [PMID: 35089224 PMCID: PMC8797488 DOI: 10.1097/md.0000000000028694] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 01/04/2022] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND The number of patients with hepatocellular carcinoma (HCC) is showing a growing trend all over the world. The metabolic microenvironment has been shown to play a key role in the pathogenesis of HCC in recent studies. The expression of metabolites and metabolic processes in tumor cells can be regulated by gene regulation mediated by long non-coding RNAs (lncRNAs), the abnormal expression of which is closely related to tumor occurrence and metastasis. However, the fundamental mechanism of applying metabolism-related lncRNAs to predicting HCC is still unclear. METHODS With the complete RNA sequence data and clinical data obtained from The Cancer Genome Atlas database and metabolism-related genes downloaded from the Kyoto Encyclopedia of Genes and Genomes database, with false discovery rate < 0.001, log fold change > 1.5 selected as the screening criteria for lncRNA, the relationship between the expression level of metabolism-related LncRNAs (MRLs) and the overall survival rate was determined by the Univariate Cox regression analyses with the establishment of the metabolic prognosis model by the application of Multivariate Cox regression analyses, revealing the different biological processes and signaling pathways in both high-risk groups and low-risk groups by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and gene set enrichment analysis, leading the expression of lncRNA to be assessed by the reverse transcription-polymerase chain reaction results. RESULTS The overall survival rate of HCC patients is significantly correlated with signature of 5-MRLs. The prognosis characteristics of lncRNA reveal the relatively high death rate of patients in the high-risk groups, with the predicted signals by functional and pathway enrichment analysis related to biosynthesis, metabolic process, and metabolic pathway, with the prognostic characteristics of 5-MRLs by the combined analysis showing that it is an independent factor of HCC superior to the traditional clinical indicators in predicting the prognosis. A trend of high-expression was shown in MRLs in tumors by reverse transcription-polymerase chain reaction. CONCLUSION The new 5-MRLs as potential biomarkers provide more powerful prognostic information for HCC patients. In the future clinical treatment of HCC, it will provide doctors with more methods.
Collapse
Affiliation(s)
- Wei Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zhenfeng Deng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zongrui Jin
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Guolin Wu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jilong Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Hai Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Banghao Xu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zhang Wen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Ya Guo
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| |
Collapse
|
|
18
|
Han Z, Li K, Wu J, Wang K, Qiu C, Ye H, Cui C, Song C, Wang K, Shi J, Wang P, Zhang J. Diagnostic value of RNA for hepatocellular carcinoma: a network meta-analysis. Biomark Med 2021; 15:1755-1767. [PMID: 34783583 DOI: 10.2217/bmm-2021-0327] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 09/03/2021] [Indexed: 02/07/2023] Open
Abstract
Aim: The aim of this study was to evaluate the capacity of RNA in the diagnosis of hepatocellular carcinoma (HCC). Methods: A systematic review was conducted from PubMed, Cochrane Library, EMBASE and Web of Science databases via well-designed retrieval strategy. Subsequently, the network meta-analysis was performed by the STATA software. Results: Through statistical analysis, the three hypotheses of the network meta-analysis were established. In view of these hypotheses, the diagnostic efficacy of the three markers in HCC (HCC vs healthy people) may be consistent, and the cumulative ranking results showed such a trend: circular RNA >long noncoding RNA >microRNA. Conclusion: Circular RNA may be most effective for diagnosing HCC across the three types of RNA.
Collapse
Affiliation(s)
- Zhuo Han
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Keming Li
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Jinyu Wu
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Keyan Wang
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
- Henan Institute of Medical & Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou, 450052, China
| | - Cuipeng Qiu
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Hua Ye
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Chi Cui
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
- Henan Institute of Medical & Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou, 450052, China
| | - Chunhua Song
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Kaijuan Wang
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Jianxiang Shi
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
- Henan Institute of Medical & Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou, 450052, China
| | - Peng Wang
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Jianying Zhang
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
- Henan Institute of Medical & Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou, 450052, China
| |
Collapse
|
|
19
|
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.
Collapse
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
| |
Collapse
|
|
20
|
Identification of Long Noncoding RNAs lnc-DC in Plasma as a New Biomarker for Primary Sjögren's Syndrome. J Immunol Res 2021; 2020:9236234. [PMID: 33123604 PMCID: PMC7585659 DOI: 10.1155/2020/9236234] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 08/12/2020] [Accepted: 09/28/2020] [Indexed: 12/12/2022] Open
Abstract
Objective To evaluate the plasma levels of lnc-DC in primary Sjögren's syndrome (pSS) patients and investigate the potential associations between lnc-DC and disease activity. Methods In this study, we recruited 358 enrollments, including 127 pSS patients without immune thrombocytopenia (ITP), 22 pSS patients with ITP, 50 systemic lupus erythematosus (SLE) patients, and 50 patients with rheumatoid arthritis (RA) and 109 healthy individuals, from Xuzhou Central Hospital. The expression of anti-SSA and anti-SSB was detected by enzyme-linked immunosorbent assay (ELISA). Spearman rank correlation test was used to analyze the relationship between lnc-DC and pSS activity. pSS activity was measured by anti-SSA, anti-SSB antibody, erythrocyte sedimentation rate (ESR), and β2-microglobulin levels. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance of plasma lnc-DC for pSS. Results Compared with healthy controls, SLE and RA patients, the lnc-DC expression levels were significantly elevated in pSS patients (P < 0.001), especially in pSS patients with ITP (P < 0.001). As expected, we also found that the lnc-DC expression positively correlated with anti-SSA (R2 = 0.290, P < 0.001), anti-SSB (R2 = 0.172, P < 0.001), ESR level (R2 = 0.076, P = 0.002), and β2-microglobulin level (R2 = 0.070, P = 0.003) in pSS patients. ROC curves showed that plasma lnc-DC in pSS patients had an AUC 0.80 with a sensitivity of 0.75 and specificity of 0.85 at the optimum cutoff 1.06 in discriminating SLE and RA patients. In addition, the combination of lnc-DC and anti-SSA/SSB (AUC: 0.84, sensitivity: 0.79, specificity: 0.90) improved significantly the diagnostic ability of pSS patients from SLE and RA patients. In the efficacy monitoring study, levels of plasma lnc-DC were dramatically decreased after treatment (P < 0.001). Conclusion These findings highlight that plasma lnc-DC as a novel biomarker for the diagnosis of pSS and can be used to evaluate the therapeutic efficacy of pSS underwent interventional therapy.
Collapse
|
|
21
|
Long Noncoding RNA LINC01006 Facilitates Cell Proliferation, Migration, and Epithelial-Mesenchymal Transition in Lung Adenocarcinoma via Targeting the MicroRNA 129-2-3p/CTNNB1 Axis and Activating Wnt/β-Catenin Signaling Pathway. Mol Cell Biol 2021; 41:e0038020. [PMID: 33753463 DOI: 10.1128/mcb.00380-20] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Lung adenocarcinoma (LUAD) is a common type of malignancy of lung cancers. Long intergenic noncoding RNAs (lincRNAs) have emerged as crucial regulators of various cancers, including LUAD. LINC01006 is a newly discovered long noncoding RNA (lncRNA) whose function in LUAD remains to be explored. This study is to explore the role of LINC01006 in LUAD. Quantitative real-time PCR (RT-qPCR) analysis and Western blotting were used to determine the expression levels and protein levels, respectively. Functional assays and animal experiments investigated the role of LINC01006 both in vivo and in vitro. Moreover, TOP/FOP assay was performed to detect the activation of the Wnt/β-catenin signaling pathway. The interaction between LINC01006 and microRNA 29-2-3-p (miR-29-2-3-p)/catenin beta 1 (CTNNB1) was explored by RNA binding protein immunoprecipitation (RIP), RNA pulldown, luciferase reporter assays, and rescue experiments. According to the results, LINC01006 was highly expressed in LUAD tissues and cell lines. LINC01006 knockdown significantly suppressed cell proliferative, migratory, and epithelial-mesenchymal transition (EMT) capacities and tumor development. Moreover, LINC01006 enhanced CTNNB1 via sequestering miR-129-2-3p and activated the Wnt/β-catenin pathway in LUAD. Overall, LINC01006 promotes LUAD development via activating the Wnt/β-catenin pathway, implying that LINC01006 might be a promising biomarker for LUAD treatment.
Collapse
|
|
22
|
Dong XH, Dai D, Yang ZD, Yu XO, Li H, Kang H. S100 calcium binding protein A6 and associated long noncoding ribonucleic acids as biomarkers in the diagnosis and staging of primary biliary cholangitis. World J Gastroenterol 2021; 27:1973-1992. [PMID: 34007134 PMCID: PMC8108032 DOI: 10.3748/wjg.v27.i17.1973] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 01/23/2021] [Accepted: 03/10/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Primary biliary cholangitis (PBC) is a chronic and slowly progressing cholestatic disease, which causes damage to the small intrahepatic bile duct by immuno-regulation, and may lead to cholestasis, liver fibrosis, cirrhosis and, eventually, liver failure.
AIM To explore the potential diagnosis and staging value of plasma S100 calcium binding protein A6 (S100A6) messenger ribonucleic acid (mRNA), LINC00312, LINC00472, and LINC01257 in primary biliary cholangitis.
METHODS A total of 145 PBC patients and 110 healthy controls (HCs) were enrolled. Among them, 80 PBC patients and 60 HCs were used as the training set, and 65 PBC patients and 50 HCs were used as the validation set. The relative expression levels of plasma S100A6 mRNA, long noncoding ribonucleic acids LINC00312, LINC00472 and LINC01257 were analyzed using quantitative reverse transcription-polymerase chain reaction. The bile duct ligation (BDL) mouse model was used to simulate PBC. Then double immunofluorescence was conducted to verify the overexpression of S100A6 protein in intrahepatic bile duct cells of BDL mice. Human intrahepatic biliary epithelial cells were treated with glycochenodeoxycholate to simulate the cholestatic environment of intrahepatic biliary epithelial cells in PBC.
RESULTS The expression of S100A6 protein in intrahepatic bile duct cells was up-regulated in the BDL mouse model compared with sham mice. The relative expression levels of plasma S100A6 mRNA, log10 LINC00472 and LINC01257 were up-regulated while LINC00312 was down-regulated in plasma of PBC patients compared with HCs (3.01 ± 1.04 vs 2.09 ± 0.87, P < 0.0001; 2.46 ± 1.03 vs 1.77 ± 0.84, P < 0.0001; 3.49 ± 1.64 vs 2.37 ± 0.96, P < 0.0001; 1.70 ± 0.33 vs 2.07 ± 0.53, P < 0.0001, respectively). The relative expression levels of S100A6 mRNA, LINC00472 and LINC01257 were up-regulated and LINC00312 was down-regulated in human intrahepatic biliary epithelial cells treated with glycochenodeoxycholate compared with control (2.97 ± 0.43 vs 1.09 ± 0.08, P = 0.0018; 2.70 ± 0.26 vs 1.10 ± 0.10, P = 0.0006; 2.23 ± 0.21 vs 1.10 ± 0.10, P = 0.0011; 1.20 ± 0.04 vs 3.03 ± 0.15, P < 0.0001, respectively). The mean expression of S100A6 in the advanced stage (III and IV) of PBC was up-regulated compared to that in HCs and the early stage (II) (3.38 ± 0.71 vs 2.09 ± 0.87, P < 0.0001; 3.38 ± 0.71 vs 2.57 ± 1.21, P = 0.0003, respectively); and in the early stage (II), it was higher than that in HCs (2.57 ± 1.21 vs 2.09 ± 0.87, P = 0.03). The mean expression of LINC00312 in the advanced stage was lower than that in the early stage and HCs (1.39 ± 0.29 vs 1.56 ± 0.33, P = 0.01; 1.39 ± 0.29 vs 2.07 ± 0.53, P < 0.0001, respectively); in addition, the mean expression of LINC00312 in the early stage was lower than that in HCs (1.56 ± 0.33 vs 2.07 ± 0.53, P < 0.0001). The mean expression of log10 LINC00472 in the advanced stage was higher than those in the early stage and HCs (2.99 ± 0.87 vs 1.81 ± 0.83, P < 0.0001; 2.99 ± 0.87 vs 1.77 ± 0.84, P < 0.0001, respectively). The mean expression of LINC01257 in both the early stage and advanced stage were up-regulated compared with HCs (3.88 ± 1.55 vs 2.37 ± 0.96, P < 0.0001; 3.57 ± 1.79 vs 2.37 ± 0.96, P < 0.0001, respectively). The areas under the curves (AUC) for S100A6, LINC00312, log10 LINC00472 and LINC01257 in PBC diagnosis were 0.759, 0.7292, 0.6942 and 0.7158, respectively. Furthermore, the AUC for these four genes in PBC staging were 0.666, 0.661, 0.839 and 0.5549, respectively. The expression levels of S100A6 mRNA, log10 LINC00472, and LINC01257 in plasma of PBC patients were decreased (2.35 ± 1.02 vs 3.06 ± 1.04, P = 0.0018; 1.99 ± 0.83 vs 2.33 ± 0.96, P = 0.036; 2.84 ± 0.92 vs 3.69 ± 1.54, P = 0.0006), and the expression level of LINC00312 was increased (1.95 ± 0.35 vs 1.73 ± 0.32, P = 0.0007) after treatment compared with before treatment using the paired t-test. Relative expression of S100A6 mRNA was positively correlated with log10 LINC00472 (r = 0.683, P < 0.0001); serum level of collagen type IV was positively correlated with the relative expression of log10 LINC00472 (r = 0.482, P < 0.0001); relative expression of S100A6 mRNA was positively correlated with the serum level of collagen type IV (r = 0.732, P < 0.0001). The AUC for the four biomarkers obtained in the validation set were close to the training set.
CONCLUSION These four genes may potentially act as novel biomarkers for the diagnosis of PBC. Moreover, LINC00472 acts as a potential biomarker for staging in PBC.
Collapse
Affiliation(s)
- Xi-Hua Dong
- Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Di Dai
- Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Zhi-Dong Yang
- Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Xiao-Ou Yu
- Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Hua Li
- Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Hui Kang
- Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| |
Collapse
|
|
23
|
Ghafouri-Fard S, Gholipour M, Hussen BM, Taheri M. The Impact of Long Non-Coding RNAs in the Pathogenesis of Hepatocellular Carcinoma. Front Oncol 2021; 11:649107. [PMID: 33968749 PMCID: PMC8097102 DOI: 10.3389/fonc.2021.649107] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 03/22/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is among the utmost deadly human malignancies. This type of cancer has been associated with several environmental, viral, and lifestyle risk factors. Among the epigenetic factors which contribute in the pathogenesis of HCC is dysregulation of long non-coding RNAs (lncRNAs). These transcripts modulate expression of several tumor suppressor genes and oncogenes and alter the activity of cancer-related signaling axes. Several lncRNAs such as NEAT1, MALAT1, ANRIL, and SNHG1 have been up-regulated in HCC samples. On the other hand, a number of so-called tumor suppressor lncRNAs namely CASS2 and MEG3 are down-regulated in HCC. The interaction between lncRNAs and miRNAs regulate expression of a number of mRNA coding genes which are involved in the pathogenesis of HCC. H19/miR-15b/CDC42, H19/miR-326/TWIST1, NEAT1/miR-485/STAT3, MALAT1/miR-124-3p/Slug, MALAT1/miR-195/EGFR, MALAT1/miR-22/SNAI1, and ANRIL/miR-144/PBX3 axes are among functional axes in the pathobiology of HCC. Some genetic polymorphisms within non-coding regions of the genome have been associated with risk of HCC in certain populations. In the current paper, we describe the recent finding about the impact of lncRNAs in HCC.
Collapse
Affiliation(s)
- Soudeh Ghafouri-Fard
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahdi Gholipour
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bashdar Mahmud Hussen
- Pharmacognosy Department, College of Pharmacy, Hawler Medical University, Erbil, Iraq
| | - Mohammad Taheri
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
24
|
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.
Collapse
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
| |
Collapse
|
|
25
|
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.
Collapse
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.)
| |
Collapse
|
|
26
|
Chao Y, Jin J, Wang L, Jin X, Yang L, Zhang B. Transcriptome Analysis of lncRNA-mRNA Interactions in Chronic Atrophic Gastritis. Front Genet 2021; 11:612951. [PMID: 33505433 PMCID: PMC7831747 DOI: 10.3389/fgene.2020.612951] [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: 10/02/2020] [Accepted: 12/03/2020] [Indexed: 12/21/2022] Open
Abstract
The aim of this study was to identify prognosis-related differentially expressed lncRNAs and mRNAs in chronic atrophic gastritis (CAG). By analysis of high-throughput whole-transcriptome sequencing data, the levels of lncRNAs and mRNAs between CAG and chronic non-atrophic gastritis were compared pairwisely. In total, 97,282 lncRNA transcripts and 20,307 mRNA transcripts were acquired, including 50 upregulated and 66 downregulated lncRNAs and 377 upregulated and 763 downregulated mRNAs in CAG (p < 0.05, fold change ≥ 2). Moreover, the interactions of the differentially expressed genes in CAG were investigated by gene ontology enrichment analysis, showing that the enriched genes are involved in many biological processes, such as MAP kinase activity, heat generation, and protein modification processes. Through the construction of co-expression networks of the differentially expressed genes in CAG, three critical lncRNAs nodes were identified as potential key factors in CAG. Eight mRNAs common in both the co-expression network and the protein-protein interaction network were selected via Venn analysis, including DGKA, EIF6, HKDC1, DHRS11, 1, KRT15, TESPA1, and CDHR2. Finally, the expression levels of five differentially expressed lncRNAs in CAG were confirmed by quantitative real-time polymerase chain reaction. In conclusion, this study presents novel promising biomarkers for the diagnosis of CAG.
Collapse
Affiliation(s)
- Yang Chao
- Department of Gastroendoscopy, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Jingpeng Jin
- Department of Gastroendoscopy, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Liqiang Wang
- Department of Gastroendoscopy, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xiya Jin
- Department of Gastroendoscopy, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Lei Yang
- Department of Gastroendoscopy, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Bin Zhang
- Department of Gastroendoscopy, China-Japan Union Hospital of Jilin University, Changchun, China
| |
Collapse
|
|
27
|
Circulating non-coding RNA cluster predicted the tumorigenesis and development of colorectal carcinoma. Aging (Albany NY) 2020; 12:23047-23066. [PMID: 33234723 PMCID: PMC7746361 DOI: 10.18632/aging.104055] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 08/27/2020] [Indexed: 12/24/2022]
Abstract
Carcinoembryonic antigen (CEA) is the most significant plasma biomarker in colorectal cancer (CRC), which is mainly used to diagnose and monitor the recurrence of CRC. However, due to the low sensitivity of CEA, it is more recommended for postoperative surveillance rather than early diagnosis. It is necessary to find efficient biomarkers for CRC. In this study, the expression of plasma non-coding RNAs was confirmed in three independent cohorts with total 1201 participants. First, 12 non-coding RNAs were screened from 9 plasma samples by using microarray. The expression of selected non-coding RNAs was further validated by multiphase detection and risk score analysis. We found that miR-20b-5p, miR-329-3p, miR-374b-5p, miR-503-5p, XLOC_001120 and ENSG00000243766.2 were significantly elevated in CRC plasma, and the AUC in training and validation set was 0.996 and 0.954, respectively. Moreover, miR-20b-5p, miR-329-3p and miR-503-5p were found elevated in plasma from larger tumors (5 cm as the cutoff) in CRC patients, and the merged AUC in training and validation set was 0.896 and 0.881. In conclusion, a panel of 6 non-coding RNAs showed their important clinical value for the early diagnosis of CRC. Among, miR-20b-5p, miR-329-3p and miR-503-5p might be the potential markers for evaluating larger tumor size of CRC.
Collapse
|
|
28
|
Zhao J, Zeng XB, Zhang HY, Xiang JW, Liu YS. Long non-coding RNA FOXD2-AS1 promotes cell proliferation, metastasis and EMT in glioma by sponging miR-506-5p. Open Med (Wars) 2020; 15:921-931. [PMID: 33336050 PMCID: PMC7711959 DOI: 10.1515/med-2020-0175] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 05/09/2020] [Accepted: 05/11/2020] [Indexed: 12/13/2022] Open
Abstract
Long non-coding RNA forkhead box D2 adjacent opposite strand RNA 1 (FOXD2-AS1) has emerged as a potential oncogene in several tumors. However, its biological function and potential regulatory mechanism in glioma have not been fully investigated to date. In the present study, RT-qPCR was conducted to detect the levels of FOXD2-AS1 and microRNA (miR)-506-5p, and western blot assays were performed to measure the expression of CDK2, cyclinE1, P21, matrix metalloproteinase (MMP)7, MMP9, N-cadherin, E-cadherin and vimentin in glioma cells. A luciferase reporter assay was performed to verify the direct targeting of miR-506-5p by FOXD2-AS1. Subsequently, cell viability was analyzed using the CCK-8 assay. Cell migration and invasion were analyzed using Transwell and wound healing assays, respectively. The results demonstrated that FOXD2-AS1 was significantly overexpressed in glioma cells, particularly in U251 cells. Knockdown of FOXD2-AS1 in glioma cells significantly inhibited cell proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) and regulated the expression of CDK2, cyclinE1, P21, MMP7 and MMP9. Next, a possible mechanism for these results was explored, and it was observed that FOXD2-AS1 binds to and negatively regulates miR-506-5p, which is known to be a tumor-suppressor gene in certain human cancer types. Furthermore, overexpression of miR-506-5p significantly inhibited cell proliferation, migration, invasion and EMT, and these effects could be reversed by transfecting FOXD2-AS1 into the cells. In conclusion, our data suggested that FOXD2-AS1 contributed to glioma proliferation, metastasis and EMT via competitively binding to miR-506-5p. FOXD2-AS1 may be a promising target for therapy in patients with glioma.
Collapse
Affiliation(s)
- Juan Zhao
- Department of Clinical Laboratory, East Hospital of Sichuan People's Hospital, Sichuan Academy of Medical Sciences, No. 585 Honghe North Road, Chengdu, Sichuan, 610101, China
| | - Xue-Bin Zeng
- Department of Outpatient, East Hospital of Sichuan People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, 610101, China
| | - Hong-Yan Zhang
- Department of Clinical Laboratory, East Hospital of Sichuan People's Hospital, Sichuan Academy of Medical Sciences, No. 585 Honghe North Road, Chengdu, Sichuan, 610101, China
| | - Jie-Wei Xiang
- Department of Clinical Laboratory, East Hospital of Sichuan People's Hospital, Sichuan Academy of Medical Sciences, No. 585 Honghe North Road, Chengdu, Sichuan, 610101, China
| | - Yu-Song Liu
- Department of Clinical Laboratory, East Hospital of Sichuan People's Hospital, Sichuan Academy of Medical Sciences, No. 585 Honghe North Road, Chengdu, Sichuan, 610101, China
| |
Collapse
|
|
29
|
Kim SS, Baek GO, Ahn HR, Sung S, Seo CW, Cho HJ, Nam SW, Cheong JY, Eun JW. Serum small extracellular vesicle-derived LINC00853 as a novel diagnostic marker for early hepatocellular carcinoma. Mol Oncol 2020; 14:2646-2659. [PMID: 32525601 PMCID: PMC7530776 DOI: 10.1002/1878-0261.12745] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 05/25/2020] [Accepted: 06/04/2020] [Indexed: 02/06/2023] Open
Abstract
This study aimed to identify novel long noncoding RNA (lncRNA) biomarkers for hepatocellular carcinoma (HCC) using publicly available tissue genomic datasets and validate their diagnostic utility for early-stage HCC. Differentially expressed lncRNAs between 371 HCC and 50 nontumor tissues were obtained from The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA_LIHC) project. Subsequently, the expression of the serum- and extracellular vesicle (EV)-derived lncRNA was assessed in 10 patients with HCC and 10 healthy controls using RT-qPCR. The candidate lncRNAs were validated in 90 HCC and 92 non-HCC (29 healthy control, 28 chronic hepatitis, 35 liver cirrhosis) patients. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated for the candidate lncRNAs and the current HCC biomarker, alpha-fetoprotein (AFP). SFTA1P, HOTTIP, HAGLROS, LINC01419, HAGLR, CRNDE, and LINC00853 were markedly upregulated in HCC in TCGA_LIHC dataset. Among them, LINC00853 has not been reported in relation to HCC before. In patients with HCC, only expression of small EV-derived LINC00853 (EV-LINC00853) was increased. EV-LINC00853 showed excellent discriminatory ability in the diagnosis of all-stage HCC (AUC = 0.934, 95% confidence interval = 0.887-0.966). Moreover, using a 14-fold increase and 20 ng·mL-1 as cutoffs for EV-LINC00853 expression and AFP level, respectively, EV-LINC00853 was found to have a sensitivity of 93.75% and specificity of 89.77%, while AFP showed only 9.38% sensitivity and 72.73% specificity for the diagnosis of early-stage HCC (mUICC stage I). EV-LINC00853 had a positivity of 97% and 67% in AFP-negative and AFP-positive early HCC, respectively. Serum EV-derived LINC00853 may be a novel potential diagnostic biomarker for early HCC, especially for AFP-negative HCC.
Collapse
Affiliation(s)
- Soon Sun Kim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Geum Ok Baek
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Hye Ri Ahn
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.,Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea
| | - Suna Sung
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.,Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea
| | - Chul Won Seo
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.,Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea
| | - Hyo Jung Cho
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Suk Woo Nam
- Functional RNomics Research Center, The Catholic University of Korea, Seoul, South Korea.,Department of Biomedicine & Health Sciences, Graduate School of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Jae Youn Cheong
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Jung Woo Eun
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| |
Collapse
|
|
30
|
Luo T, Gao Y, Zhangyuan G, Xu X, Xue C, Jin L, Zhang W, Zhu C, Sun B, Qin X. lncRNA PCBP1-AS1 Aggravates the Progression of Hepatocellular Carcinoma via Regulating PCBP1/PRL-3/AKT Pathway. Cancer Manag Res 2020; 12:5395-5408. [PMID: 32753957 PMCID: PMC7352448 DOI: 10.2147/cmar.s249657] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 06/10/2020] [Indexed: 12/30/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) is a very belligerent primary liver tumor with high metastatic potential. Aberrant expression of lncRNAs drives tumorous invasion and metastasis. Whether lncRNAs engage mechanisms of liver cancer metastasis remains largely unexplored. Patients and Methods We collected HCC tissues from the tumors and their adjacent normal samples in the Chinese population and analyzed the levels of lncRNAs by microarray analysis. The gain- and loss-of-function analysis demonstrated that PCBP1-AS1 accelerated tumorous growth and metastasis in vivo and in vitro. Moreover, we used RNA-pulldown assay to show that PCBP1-AS1 physically interacted with polyC-RNA-binding protein 1 (PCBP1); meanwhile, PCBP1-AS1 was indeed detected in RIP with the PCBP1 antibody. Mechanistically, we first explored the relationship between PCBP1‐AS1 and PCBP1 in HCC cell lines. Results Here we show that PCBP1-AS1, identified by microarray analysis on pre- and post-operative HCC plasma specimens, was highly expressed in human HCC, clinically verified as a prometastatic factor and markedly associated with poor prognosis in patients with hepatocellular carcinoma. PCBP1‐AS1 was negatively related with PCBP1 at the messenger RNA and protein expression levels. PCBP1-AS1 triggered PRL-3 and AKT in HCC tumor cells. Additionally, the double knockout of PCBP1 and PCBP1-AS1 abolished the PCBP1-AS1-induced PRL-3-AKT signalling pathway activation. Conclusion The upregulation of PCBP1-AS1 enhances proliferation and metastasis in HCC, thus regulating the PCBP1-PRL-3-AKT signalling pathway.
Collapse
Affiliation(s)
- Tianping Luo
- Department of Hepatobiliary Surgery, The Affiliated Changzhou NO. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213164, People's Republic of China
| | - Yuan Gao
- Department of Hepatobiliary Surgery, The Affiliated Changzhou NO. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213164, People's Republic of China
| | - Guangyan Zhangyuan
- Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, People's Republic of China
| | - Xiaoliang Xu
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province 210008, People's Republic of China
| | - Cailin Xue
- Department of Hepatobiliary Surgery, The Affiliated Changzhou NO. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213164, People's Republic of China
| | - Lei Jin
- Department of Hepatobiliary Surgery, The Affiliated Changzhou NO. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213164, People's Republic of China
| | - Wenjie Zhang
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province 210008, People's Republic of China
| | - Chunfu Zhu
- Department of Hepatobiliary Surgery, The Affiliated Changzhou NO. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213164, People's Republic of China
| | - Beicheng Sun
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province 210008, People's Republic of China
| | - Xihu Qin
- Department of Hepatobiliary Surgery, The Affiliated Changzhou NO. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213164, People's Republic of China
| |
Collapse
|
|
31
|
Russano M, Napolitano A, Ribelli G, Iuliani M, Simonetti S, Citarella F, Pantano F, Dell'Aquila E, Anesi C, Silvestris N, Argentiero A, Solimando AG, Vincenzi B, Tonini G, Santini D. Liquid biopsy and tumor heterogeneity in metastatic solid tumors: the potentiality of blood samples. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2020; 39:95. [PMID: 32460897 PMCID: PMC7254767 DOI: 10.1186/s13046-020-01601-2] [Citation(s) in RCA: 155] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 05/20/2020] [Indexed: 12/14/2022]
Abstract
In a large number of cancer types, treatment selection depends on the presence of specific tumor biomarkers. Due to the dynamic nature of cancer, very often these predictive biomarkers are not uniformly present in all cancer cells. Tumor heterogeneity represents indeed one of the main causes of therapeutic failure, and its decoding remains a major ongoing challenge in the field. Liquid biopsy is the sampling and analysis of non-solid biological tissue often through rapid and non-invasive methods, which allows the assessment in real-time of the evolving landscape of cancer. Samples can be obtained from blood and most other bodily fluids. A blood-based liquid biopsy can capture circulating tumor cells and leukocytes, as well as circulating tumor-derived nucleic acids. In this review, we discuss the current and possibly future applications of blood-based liquid biopsy in oncology, its advantages and its limitations in clinical practice. We specifically focused on its role as a tool to capture tumor heterogeneity in metastatic cancer patients.
Collapse
Affiliation(s)
- Marco Russano
- Department of Medical Oncology, Campus Bio-Medico University of Rome, Álvaro del Portillo, 21, 00128, Rome, Italy
| | - Andrea Napolitano
- Department of Medical Oncology, Campus Bio-Medico University of Rome, Álvaro del Portillo, 21, 00128, Rome, Italy
| | - Giulia Ribelli
- Department of Medical Oncology, Campus Bio-Medico University of Rome, Álvaro del Portillo, 21, 00128, Rome, Italy.
| | - Michele Iuliani
- Department of Medical Oncology, Campus Bio-Medico University of Rome, Álvaro del Portillo, 21, 00128, Rome, Italy
| | - Sonia Simonetti
- Department of Medical Oncology, Campus Bio-Medico University of Rome, Álvaro del Portillo, 21, 00128, Rome, Italy
| | - Fabrizio Citarella
- Department of Medical Oncology, Campus Bio-Medico University of Rome, Álvaro del Portillo, 21, 00128, Rome, Italy
| | - Francesco Pantano
- Department of Medical Oncology, Campus Bio-Medico University of Rome, Álvaro del Portillo, 21, 00128, Rome, Italy
| | - Emanuela Dell'Aquila
- Department of Medical Oncology, Campus Bio-Medico University of Rome, Álvaro del Portillo, 21, 00128, Rome, Italy
| | - Cecilia Anesi
- Department of Medical Oncology, Campus Bio-Medico University of Rome, Álvaro del Portillo, 21, 00128, Rome, Italy
| | - Nicola Silvestris
- Medical Oncology Unit, IRCCS-Istituto Tumori "Giovanni Paolo II" of Bari, 70124, Bari, Italy.,Department of Biomedical Sciences and Human Oncology, University of Bari 'Aldo Moro', 70124, Bari, Italy
| | - Antonella Argentiero
- Medical Oncology Unit, IRCCS-Istituto Tumori "Giovanni Paolo II" of Bari, 70124, Bari, Italy
| | - Antonio Giovanni Solimando
- Medical Oncology Unit, IRCCS-Istituto Tumori "Giovanni Paolo II" of Bari, 70124, Bari, Italy.,Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine 'G. Baccelli', University of Bari Medical School, 70124, Bari, Italy
| | - Bruno Vincenzi
- Department of Medical Oncology, Campus Bio-Medico University of Rome, Álvaro del Portillo, 21, 00128, Rome, Italy
| | - Giuseppe Tonini
- Department of Medical Oncology, Campus Bio-Medico University of Rome, Álvaro del Portillo, 21, 00128, Rome, Italy
| | - Daniele Santini
- Department of Medical Oncology, Campus Bio-Medico University of Rome, Álvaro del Portillo, 21, 00128, Rome, Italy
| |
Collapse
|
|
32
|
Yuan L, Guo F, Wang L, Zou Q. Prediction of tumor metastasis from sequencing data in the era of genome sequencing. Brief Funct Genomics 2020; 18:412-418. [PMID: 31204784 DOI: 10.1093/bfgp/elz010] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 02/22/2019] [Accepted: 04/26/2019] [Indexed: 02/01/2023] Open
Abstract
Tumor metastasis is the key reason for the high mortality rate of tumor. Growing number of scholars have begun to pay attention to the research on tumor metastasis and have achieved satisfactory results in this field. The advent of the era of sequencing has enabled us to study cancer metastasis at the molecular level, which is essential for understanding the molecular mechanism of metastasis, identifying diagnostic markers and therapeutic targets and guiding clinical decision-making. We reviewed the metastasis-related studies using sequencing data, covering detection of metastasis origin sites, determination of metastasis potential and identification of distal metastasis sites. These findings include the discovery of relevant markers and the presentation of prediction tools. Finally, we discussed the challenge of studying metastasis considering the difficulty of obtaining metastatic cancer data, the complexity of tumor heterogeneity and the uncertainty of sample labels.
Collapse
Affiliation(s)
- Linlin Yuan
- College of Intelligence and Computing, Tianjin University, Tianjin, China
| | - Fei Guo
- College of Intelligence and Computing, Tianjin University, Tianjin, China
| | - Lei Wang
- College of Computer Engineering & Applied Mathematics, Changsha University, Changsha, China
| | - Quan Zou
- Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, China.,Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, China
| |
Collapse
|
|
33
|
Classical and Deep Learning Paradigms for Detection and Validation of Key Genes of Risky Outcomes of HCV. ALGORITHMS 2020. [DOI: 10.3390/a13030073] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Hepatitis C virus (HCV) is one of the most dangerous viruses worldwide. It is the foremost cause of the hepatic cirrhosis, and hepatocellular carcinoma, HCC. Detecting new key genes that play a role in the growth of HCC in HCV patients using machine learning techniques paves the way for producing accurate antivirals. In this work, there are two phases: detecting the up/downregulated genes using classical univariate and multivariate feature selection methods, and validating the retrieved list of genes using Insilico classifiers. However, the classification algorithms in the medical domain frequently suffer from a deficiency of training cases. Therefore, a deep neural network approach is proposed here to validate the significance of the retrieved genes in classifying the HCV-infected samples from the disinfected ones. The validation model is based on the artificial generation of new examples from the retrieved genes’ expressions using sparse autoencoders. Subsequently, the generated genes’ expressions data are used to train conventional classifiers. Our results in the first phase yielded a better retrieval of significant genes using Principal Component Analysis (PCA), a multivariate approach. The retrieved list of genes using PCA had a higher number of HCC biomarkers compared to the ones retrieved from the univariate methods. In the second phase, the classification accuracy can reveal the relevance of the extracted key genes in classifying the HCV-infected and disinfected samples.
Collapse
|
|
34
|
Unfried JP, Fortes P. LncRNAs in HCV Infection and HCV-Related Liver Disease. Int J Mol Sci 2020; 21:ijms21062255. [PMID: 32214045 PMCID: PMC7139329 DOI: 10.3390/ijms21062255] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 03/19/2020] [Accepted: 03/20/2020] [Indexed: 12/14/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) are transcripts with poor coding capacity that may interact with proteins, DNA, or other RNAs to perform structural and regulatory functions. The lncRNA transcriptome changes significantly in most diseases, including cancer and viral infections. In this review, we summarize the functional implications of lncRNA-deregulation after infection with hepatitis C virus (HCV). HCV leads to chronic infection in many patients that may progress to liver cirrhosis and hepatocellular carcinoma (HCC). Most lncRNAs deregulated in infected cells that have been described function to potentiate or block the antiviral response and, therefore, they have a great impact on HCV viral replication. In addition, several lncRNAs upregulated by the infection contribute to viral release. Finally, many lncRNAs have been described as deregulated in HCV-related HCC that function to enhance cell survival, proliferation, and tumor progression by different mechanisms. Interestingly, some HCV-related HCC lncRNAs can be detected in bodily fluids, and there is great hope that they could be used as biomarkers to predict cancer initiation, progression, tumor burden, response to treatment, resistance to therapy, or tumor recurrence. Finally, there is high confidence that lncRNAs could also be used to improve the suboptimal long-term outcomes of current HCC treatment options.
Collapse
Affiliation(s)
| | - P. Fortes
- Correspondence: ; Tel.: +34-948194700
| |
Collapse
|
|
35
|
LncRNA GAS5-AS1 inhibits glioma proliferation, migration, and invasion via miR-106b-5p/TUSC2 axis. Hum Cell 2020; 33:416-426. [PMID: 32072565 DOI: 10.1007/s13577-020-00331-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 02/10/2020] [Indexed: 01/13/2023]
Abstract
Glioma is one of the most common malignant tumors and shows a high metastasis rate and poor prognosis. Abnormal expression of long non-coding RNAs (lncRNAs) contributes to various human tumors including gliomas. This study aimed to investigate the regulatory role of the antisense RNA of growth arrest special 5 (GAS5-AS1), a novel lncRNA, in gliomas. Expression of GAS5-AS1 and microRNA-106b-5p (miR-106b-5p) in glioma tissues and cells was detected by quantitative reverse transcription PCR, northern blotting, or fluorescent in situ hybridization. Cell proliferation, migration, and invasion were analyzed by CCK-8 and Transwell assays. BALB/c nude mice were used to establish a glioma xenograft animal model by subcutaneous injection of U251 cells transfected with small interfering RNA targeting GAS5-AS1. A dual-luciferase reporter assay was conducted to confirm the targeting relationship between GAS5-AS1 and miR-106b-5p. GAS5-AS1 expression was downregulated in glioma tissues and cells, and upregulation of GAS5-AS1 expression inhibited glioma cell proliferation, migration, and invasion. GAS5-AS1 expression was correlated with the glioma tumor grade. In nude mice, upregulation of GAS5-AS1 markedly suppressed glioma tumor growth. GAS5-AS1 overexpression significantly increased the miR-106b-5p level in glioma cells, and GAS5-AS1 expression was negatively related to miR-106b-5p expression in glioma tissues. Overexpression of miR-106b-5p reversed the inhibitory effects of GAS5-AS1 upregulation on glioma cell proliferation and metastasis, while restoration of TUSC2 rescued the proliferation and invasion of glioma cells transfected with miR-106b-5p mimics. In summary, lncRNA GAS5-AS1 inhibited glioma proliferation, migration, and invasion by sponging miR-106b-5p and regulating the expression of TUSC2. Our results suggest GAS5-AS1 as a novel target for the treatment and prognosis prediction of gliomas.
Collapse
|
|
36
|
Zha Z, Han Q, Liu W, Huo S. lncRNA GAS8-AS1 downregulates lncRNA UCA1 to inhibit osteosarcoma cell migration and invasion. J Orthop Surg Res 2020; 15:38. [PMID: 32013985 PMCID: PMC6998179 DOI: 10.1186/s13018-020-1550-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Accepted: 01/09/2020] [Indexed: 11/18/2022] Open
Abstract
Background Osteosarcoma (OS) is the most common type of primary bone tumor that mainly affects adolescents and young adults. The present study explored the role of lncRNA GAS8-AS1 in OS. Methods A total of 48 OS patients were selected from the 82 OS patients admitted by Luoyang Orthopedic Hospital of Henan Province between May 2010 and May 2013. Transient cell transfections, Transwell cell migration and invasion assay, RT-qPCR, and patient follow-up were carried out during the research. Results The results showed that GAS8-AS1 was downregulated, while UCA1 was upregulate in cancer tissues in comparison to adjacent non-cancer tissues of OS patients. GAS8-AS1 was not affected by clinical stage. Follow-up study showed that downregulated GAS8-AS1 in cancer tissues was closely correlated with poor survival. GAS8-AS1 and UCA1 were inversely correlated in cancer tissues. Overexpression of UCA1 failed to affect the expression of GAS8-AS1, while overexpression of GAS8-AS1 led to downregulated expression of UCA1 in OS cells, while the molecular mediators between these two lncRNAs are unknown. Overexpression of GAS8-AS1 did not affect OS cell proliferation but significantly inhibited cancer cell migration and invasion. Overexpression of UCA1 promoted the migration and invasion of OS cells and attenuated the effects of overexpressing GAS8-AS1. Conclusions Therefore, GAS8-AS1 may inhibit OS cell migration and invasion by downregulating oncogenic UCA1.
Collapse
Affiliation(s)
- Zhuqing Zha
- Department of Orthopedics, Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province, No.100 Yongping Road, Zhengzhou City, Henan Province, 450016, People's Republic of China
| | - Qingmin Han
- Department of Orthopedics, Guangzhou University of Chinese Medicine Third Affiliated Hospital, Guangzhou City, Guangdong Province, 510375, People's Republic of China
| | - Wenjing Liu
- Department of Orthopedics, Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province, No.100 Yongping Road, Zhengzhou City, Henan Province, 450016, People's Republic of China
| | - Shaochuan Huo
- Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, No. 6001, North Ring Road, Futian District, Shenzhen City, Guangdong Province, 518048, People's Republic of China.
| |
Collapse
|
|
37
|
Wang W, Wei C. Advances in the early diagnosis of hepatocellular carcinoma. Genes Dis 2020; 7:308-319. [PMID: 32884985 PMCID: PMC7452544 DOI: 10.1016/j.gendis.2020.01.014] [Citation(s) in RCA: 278] [Impact Index Per Article: 55.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 01/10/2020] [Accepted: 01/20/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers globally. In contrast to the declining death rates observed for all other common cancers such as breast, lung, and prostate cancers, the death rates for HCC continue to increase by ~2–3% per year because HCC is frequently diagnosed late and there is no curative therapy for an advanced HCC. The early diagnosis of HCC is truly a big challenge. Over the past years, the early diagnosis of HCC has relied on surveillance with ultrasonography (US) and serological assessments of alpha-fetoprotein (AFP). However, the specificity and sensitivity of US/AFP is not satisfactory enough to detect early onset HCC. Recent technological advancements offer hope for early HCC diagnosis. Herein, we review the progress made in HCC diagnostics, with a focus on emerging imaging techniques and biomarkers for early disease diagnosis.
Collapse
Affiliation(s)
- Weiyi Wang
- Xiamen Amplly Bio-engineering Co., Ltd, Xiamen, PR China
| | - Chao Wei
- Xiamen Amplly Bio-engineering Co., Ltd, Xiamen, PR China
| |
Collapse
|
|
38
|
Li X, Li C, Zhang L, Wu M, Cao K, Jiang F, Chen D, Li N, Li W. The significance of exosomes in the development and treatment of hepatocellular carcinoma. Mol Cancer 2020; 19:1. [PMID: 31901224 PMCID: PMC6942270 DOI: 10.1186/s12943-019-1085-0] [Citation(s) in RCA: 388] [Impact Index Per Article: 77.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 10/04/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most commonmalignancy. Exsome plays a significant role in the elucidation of signal transduction pathways between hepatoma cells, angiogenesis and early diagnosis of HCC. Exosomes are small vesicular structures that mediate interaction between different types of cells, and contain a variety of components (including DNA, RNA, and proteins). Numerous studies have shown that these substances in exosomes are involved in growth, metastasis and angiogenesis in liver cancer, and then inhibited the growth of liver cancer by blocking the signaling pathway of liver cancer cells. In addition, the exosomal substances could also be used as markers for screening early liver cancer. In this review, we summarized to reveal the significance of exosomes in the occurrence, development, diagnosis and treatment of HCC, which in turn might help us to further elucidate the mechanism of exosomes in HCC, and promote the use of exosomes in the clinical diagnosis and treatment of HCC.
Collapse
Affiliation(s)
- Xin Li
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Chuanyun Li
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Liping Zhang
- Department of Maternity, Yanan University Affiliated Hospital, Yanan, China
| | - Min Wu
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Ke Cao
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Feifei Jiang
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Dexi Chen
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai,Fengtai District, Beijing, 100069, China
| | - Ning Li
- Beijing Youan Hospital, Capital Medical University, Beijing, China. .,Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai,Fengtai District, Beijing, 100069, China.
| | - Weihua Li
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai,Fengtai District, Beijing, 100069, China.
| |
Collapse
|
|
39
|
Blocking lncRNA MIR155HG/miR-155-5p/-3p inhibits proliferation, invasion and migration of clear cell renal cell carcinoma. Pathol Res Pract 2019; 216:152803. [PMID: 31889587 DOI: 10.1016/j.prp.2019.152803] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 12/12/2019] [Accepted: 12/23/2019] [Indexed: 01/07/2023]
Abstract
This study aimed to investigate the effect of blocking the MIR155HG/miR-155-5p/-3p axis on proliferation, invasion and migration of clear cell renal cell carcinoma. RT-qPCR was used to detect the expression of MIR155HG, miR-155-5p, miR-155-3p in clear cell renal cell carcinoma cell lines. To study the effects of blocking LncRNA MIR155HG and interfering with miR-155-5p and miR-155-3p on the biological function. The g proliferation of tumor was detected by CCK-8, and the cell invasion and migration abilities were detected by wound healing and transwell experiments. Western blot analyzed protein levels of KI67, PCNA, MMP2 and MMP9. Furthermore, TargetScan and miRDB were used to predict the co-target gene of miR-155-3p and miR-155-5p, and the functional analysis of co-target genes was performed using the DAVID. In the current research, the expression of MIR155HG was increased in ccRCC. Interference of MIR155HG inhibited the cellular functions of ccRCC cells, which was reversed by overexpression of miR-155-3p and miR-155-5p. In addition, MIR155HG interference repressed the expression of miR-155-5p and miR-155-3p in ccRCCs, while inhibition of miR-155-5p and miR-155-3p restrained the proliferation, invasion and migration of ccRCCs. Bioinformatics software analysis showed 13 co-targeting genes of miR-155-3p and miR-155-5p. Functional analysis presented that the target genes of miR-31-3p were involved in numerous of biochemical processes and pathways.Blocking lncRNA MIR155HG/miR-155-5p/-3p inhibits proliferation, invasion and migration of renal clear cell carcinoma, which provided a new method for early diagnosis and precise treatment of ccRCC.
Collapse
|
|
40
|
Luo J, Xiong Y, Fu PF, Li EC, Qu L, Fan X, Cai ZJ, Lin AF. Exosomal long non-coding RNAs: biological properties and therapeutic potential in cancer treatment. J Zhejiang Univ Sci B 2019; 20:488-495. [PMID: 31090274 DOI: 10.1631/jzus.b1900039] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Exosomes and long non-coding RNAs (lncRNAs) are emerging as important elements contributing to a more comprehensive understanding of cancer development and progression. The discovery of lncRNAs in exosomes further indicates their bona fide biological functional roles in cancer development and drug resistance. In this review, we describe the biogenesis of exosomes and summarize the function of exosomal lncRNAs in the field of cancer research. These findings strikingly advance current knowledge of exosomal lncRNAs and suggest that they may be promising diagnostic biomarkers and therapeutic targets for cancer.
Collapse
Affiliation(s)
- Jie Luo
- Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
| | - Yan Xiong
- Department of Orthopedic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Pei-Fen Fu
- The Breast Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - En-Chun Li
- Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
| | - Lei Qu
- MOE Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou 310058, China
| | - Xiao Fan
- MOE Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou 310058, China
| | - Zhi-Jian Cai
- Institute of Immunology, and Department of Orthopaedics, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China
| | - Ai-Fu Lin
- The Breast Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.,MOE Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou 310058, China
| |
Collapse
|
|
41
|
Association between polymorphism in CDKN2B-AS1 gene and its interaction with smoking on the risk of lung cancer in a Chinese population. Hum Genomics 2019; 13:58. [PMID: 31775885 PMCID: PMC6880550 DOI: 10.1186/s40246-019-0240-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2019] [Accepted: 10/01/2019] [Indexed: 01/06/2023] Open
Abstract
Background Long non-coding RNAs became the hot spots in the carcinogenesis of various tumors. This case-control study evaluated the association between the rs2151280 in lncRNA CDKN2B-AS1 and lung cancer risk. Methods This study included 507 lung cancer patients and 542 healthy individuals. Odds ratios and their 95% confidence intervals were calculated by unconditional logistic regression analysis to evaluate the association between the rs2151280 and lung cancer risk. Results Compared with individuals carrying TT genotype, individuals carrying CC genotype of rs2151280 had a decreased risk of lung cancer (OR = 0.640, 95%CI = 0.421–0.972, P = 0.036). In the recessive model, rs2151280 CC genotype was observed to reduce the risk of lung cancer (OR = 0.684). C allele was associated with non-small cell lung cancer risk (OR = 0.674). The rs2151280 was significantly associated with lung adenocarcinoma risk (CCvsTT: OR = 0.567, 95%CI = 0.333–0.965, P = 0.037; CCvsTC+TT: OR = 0.543, 95%CI 0.330–0.893, P = 0.016, respectively). However, there was no significant association between rs2151280 and lung squamous cell carcinoma risk in five models. The quantitative analysis suggested that there were no significant interactions of rs2151280 with smoking exposure to lung cancer susceptibility. Conclusions This hospital-based case-control study suggested that CDKN2B-AS1 rs2151280 T>C was associated with the risk of lung cancer.
Collapse
|
|
42
|
Liu SY. Abnormal regulation of non-coding RNAs plays a role in development and progression of hepatocellular carcinoma. Shijie Huaren Xiaohua Zazhi 2019; 27:1107-1113. [DOI: 10.11569/wcjd.v27.i18.1107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis. Non-coding RNAs (ncRNAs) are RNAs transcribed from the genome but not translated into protein. In recent years, ncRNAs have been recognized to be key factors in tumorigenesis because of their ability to regulate multiple targets, cell proliferation, differentiation, apoptosis, and development. In this review, we discuss the pathological significance of ncRNAs (microRNAs, long-chain non-coding RNAs, and cyclic RNAs) in the development and progression of HCC. We also discuss the potential role of ncRNAs in the diagnosis and treatment of HCC.
Collapse
Affiliation(s)
- Shu-Ye Liu
- Clinical Laboratory, Tianjin Third Central Hospital, Tianjin 300170, China
| |
Collapse
|
|
43
|
Zhao Y, Kong CQ, Ye JZ, Bai T, Luo T, Wang D, Chen M, Wang HF, Wang XB, Liu JJ, Chen J, Luo HL, Li LQ. Upregulation of Long Non-Coding RNA ENST00000429227.1 Is Correlated with Poor Prognosis in Human Hepatocellular Carcinoma. Med Sci Monit 2019; 25:6539-6546. [PMID: 31472071 PMCID: PMC6738009 DOI: 10.12659/msm.916551] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs) have been shown to play an important regulatory role in many tumors. This study was designed to investigate the expression of lncRNA ENST00000429227.1 in hepatocellular carcinoma (HCC) and to determine whether the expression of lncRNA ENST00000429227.1 affects the prognosis of HCC. MATERIAL AND METHODS lncRNA ENST00000429227.1 showing differences in expression between M1 and M2 was screened by microarray expression measurements. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of lncRNA ENST00000429227.1 in 161 HCC patients. The chi-square test was used to evaluate the relationship between the expression of ENST00000429227.1 and clinicopathological parameters. A survival curve was drawn and analyzed by Kaplan-Meier method. Cox regression was used for univariate and multivariate analysis to determine whether lncRNA ENST00000429227.1 is an independent factor of the occurrence and prognosis of HCC. RESULTS A total of 3703 differentially expressed lncRNAs were obtained, of which 1777 were upregulated and 1926 were downregulated, with multiple change >1.5. The expression of lncRNA ENST00000429227.1 was upregulated in M2 cells. The expression of lncRNA ENST00000429227.1 in HCC tissues was higher than that in adjacent normal tissues (p<0.05), which was correlated with pathological parameters such as surgical margin (p=0.042), AFP (p=0.022) and Barcelona Clinic Liver Cancer (BCLC) stage (p=0.008). Survival analysis showed that high expression of lncRNA ENST00000429227.1 was associated with a decrease in overall survival (OS) rate of HCC patients. Cox regression analysis showed that high expression of ENST00000429227.1 may be an independent risk factor affecting the prognosis of HCC patients. CONCLUSIONS The results suggest that upregulation of ENST00000429227.1 is associated with poor prognosis of HCC patients, and may be a new biomarker for the diagnosis of HCC.
Collapse
Affiliation(s)
- Yuan Zhao
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Cun-Qing Kong
- Imaging Center, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Jia-Zhou Ye
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Tao Bai
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Tao Luo
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Duo Wang
- Department of Ultrasound, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Miao Chen
- Department of Ultrasound, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Hui-Feng Wang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Xiao-Bo Wang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Jun-Jie Liu
- Department of Ultrasound, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Jie Chen
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Hong-Lin Luo
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| |
Collapse
|
|
44
|
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.
Collapse
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.
| |
Collapse
|
|
45
|
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.
Collapse
Affiliation(s)
- Lavinia Alice Balaceanu
- Department of Internal Medicine, Carol Davila University of Medicine and Pharmacy, Sf. Ioan Clinical Emergency Hospital, Bucharest 42122, Romania
| |
Collapse
|
|
46
|
Zhang Z, Qiao J, Zhang D, Zhu W, Zhu J, Leng X, Li S. Noncoding RNAs Act as Tumor-Derived Molecular Components in Inducing Premetastatic Niche Formation. BIOMED RESEARCH INTERNATIONAL 2019; 2019:9258075. [PMID: 31309120 PMCID: PMC6594336 DOI: 10.1155/2019/9258075] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 05/04/2019] [Accepted: 05/27/2019] [Indexed: 12/14/2022]
Abstract
Cancer metastasis has been demonstrated as it is the culmination of a cascade of priming steps. Increasing evidence has shown that tumor-derived molecular components (TDMCs) are known as extra cellular vesicle and nonvesicle factors and serve as versatile intercellular communication vehicles which can mediate signaling in the tumor microenvironment while creating the premetastatic niche. Noncoding RNAs (ncRNAs) as one of the TDMCs have been proved in participating in the formation of the premetastatic niche. Understanding the premetastatic niche formation mechanisms through TDMCs, especially ncRNAs may open a new avenue for cancer metastasis therapeutic strategies. In this review, recent findings regarding ncRNAs function were summarized, and then the interaction with the premetastatic niche formation was studied, which highlight the potential of using ncRNAs for cancer diagnosis and therapeutic effect.
Collapse
Affiliation(s)
- Zhedong Zhang
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, 100044, China
| | - Jiao Qiao
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong, 250021, China
| | - Dafang Zhang
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, 100044, China
| | - Weihua Zhu
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, 100044, China
| | - Jiye Zhu
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, 100044, China
| | - Xisheng Leng
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, 100044, China
| | - Shu Li
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, 100044, China
| |
Collapse
|
|
47
|
Differential Plasma Expression Profiles of Long Non-Coding RNAs Reveal Potential Biomarkers for Systemic Lupus Erythematosus. Biomolecules 2019; 9:biom9060206. [PMID: 31141998 PMCID: PMC6627908 DOI: 10.3390/biom9060206] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2019] [Revised: 05/05/2019] [Accepted: 05/20/2019] [Indexed: 12/17/2022] Open
Abstract
Identify long non-coding RNAs (lncRNAs) that might serve as biomarkers for systemic lupus erythematosus (SLE) and explore the biological functions of the identified lncRNAs. In the screening phase, we examined the lncRNA expression profile of plasma samples from 24 patients with SLE and 12 healthy controls (HCs) using lncRNA microarray with pooled samples. The candidate lncRNAs were verified in individual samples by quantitative real-time (qRT)-PCR. In the independent validation stage, the identified lncRNAs were evaluated in 240 patients with SLE and 120 HCs. The identified lncRNAs were assessed further in an external validation stage including patients with rheumatoid arthritis (RA) and primary Sjögren’s syndrome (pSS). In addition, we constructed correlated expression networks including coding–non-coding co-expression and competing endogenous RNAs (ceRNAs). Plasma levels of linc0597, lnc0640, and lnc5150 were elevated in SLE patients compared with those of HCs, whereas levels of GAS5 and lnc7074 were decreased. Five lncRNAs were identified as potential SLE biomarkers with an area under the receiver operating characteristic curve (AUC) ranging from 0.604 to 0.833 in the independent validation phase. This panel of five lncRNAs had high diagnostic accuracy for SLE (AUC = 0.966) and distinguished SLE from RA and pSS (AUC = 0.683 and 0.910, respectively). Co-expression analysis showed that GAS5, lnc0640, and lnc5150 may participate in the SLE pathogenesis through the MAPK pathway. The ceRNA network indicated that GAS5, lnc0640, lnc3643, lnc6655, and lnc7074 bind competitively with microRNAs regulating the expression of target genes. Aberrant expression and related pathways suggest the important role of lncRNAs in SLE pathogenesis. In addition, the panel of five lncRNAs (GAS5, lnc7074, linc0597, lnc0640, and lnc5150) in plasma could be used as SLE biomarkers.
Collapse
|
|
48
|
LncRNAs with miRNAs in regulation of gastric, liver, and colorectal cancers: updates in recent years. Appl Microbiol Biotechnol 2019; 103:4649-4677. [PMID: 31062053 DOI: 10.1007/s00253-019-09837-5] [Citation(s) in RCA: 95] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 04/07/2019] [Accepted: 04/08/2019] [Indexed: 12/15/2022]
Abstract
Long noncoding RNA (lncRNA) is a kind of RNAi molecule composed of hundreds to thousands of nucleotides. There are several major types of functional lncRNAs which participate in some important cellular pathways. LncRNA-RNA interaction controls mRNA translation and degradation or serves as a microRNA (miRNA) sponge for silencing. LncRNA-protein interaction regulates protein activity in transcriptional activation and silencing. LncRNA guide, decoy, and scaffold regulate transcription regulators of enhancer or repressor region of the coding genes for alteration of expression. LncRNA plays a role in cellular responses including the following activities: regulation of chromatin structural modification and gene expression for epigenetic and cell function control, promotion of hematopoiesis and maturation of immunity, cell programming in stem cell and somatic cell development, modulation of pathogen infection, switching glycolysis and lipid metabolism, and initiation of autoimmune diseases. LncRNA, together with miRNA, are considered the critical elements in cancer development. It has been demonstrated that tumorigenesis could be driven by homeostatic imbalance of lncRNA/miRNA/cancer regulatory factors resulting in biochemical and physiological alterations inside the cells. Cancer-driven lncRNAs with other cellular RNAs, epigenetic modulators, or protein effectors may change gene expression level and affect the viability, immortality, and motility of the cells that facilitate cancer cell cycle rearrangement, angiogenesis, proliferation, and metastasis. Molecular medicine will be the future trend for development. LncRNA/miRNA could be one of the potential candidates in this category. Continuous studies in lncRNA functional discrepancy between cancer cells and normal cells and regional and rational genetic differences of lncRNA profiles are critical for clinical research which is beneficial for clinical practice.
Collapse
|
|
49
|
Sarfi M, Abbastabar M, Khalili E. Long noncoding RNAs biomarker-based cancer assessment. J Cell Physiol 2019; 234:16971-16986. [PMID: 30835829 DOI: 10.1002/jcp.28417] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 02/04/2019] [Accepted: 02/14/2019] [Indexed: 12/18/2022]
Abstract
Cancer diagnosis have mainly relied on the incorporation of molecular biomarkers as part of routine diagnostic tool. The molecular alteration ranges from those involving DNA, RNA, noncoding RNAs (microRNAs and long noncoding RNAs [lncRNAs]) and proteins. lncRNAs are recently discovered noncoding endogenous RNAs that critically regulates the development, invasion, and metastasis of cancer cells. They are dysregulated in different types of malignancies and have the potential to serve as diagnostic markers for cancer. The expression of noncoding RNAs is altered following many diseases, and besides, some of them can be secreted from the cells into the circulation following the apoptotic and necrotic cell death. These secreted noncoding RNAs are known as cell free RNA. These RNAs can be secreted from the cell through the apoptotic body, extracellular vesicles including microvesicle and exosome, and bind to proteins. Since, lncRNAs display high organ and cell specificity, can be found in the blood, urine, tumor tissue, or other tissues or bodily fluids of some patients with cancer, this review summarizes the most significant and up-to-date findings of research on lncRNAs involvement in different cancers, focusing on the potential of cancer-related lncRNAs as biomarkers for diagnosis, prognosis, and therapy.
Collapse
Affiliation(s)
- Mohammad Sarfi
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Students Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Abbastabar
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Students Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ehsan Khalili
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
50
|
Chatterjee M, Sengupta S. Emerging roles of long non-coding RNAs in cancer. J Biosci 2019; 44:22. [PMID: 30837373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Cancer is a physiological condition that has both the endogenous and exogenous influences on its progression. It originates from unusual cell growth, where the cells undergo massive genetic alterations, bypass the signaling machinery and compromise its genetic cohesion. Literature has well narrated the DNA damage studies including driver mutations that interfere with the treatment strategies. However, with evolving medical excellence, recent day studies are trying to unveil the contribution of RNAs in the progression of tumor malignancies. A number of non-coding RNAs have been identified as an active component in cancer genomics. This article aims to review the role of long non-coding RNAs in the spectra of cancers and its prognostic value as the biomarkers in molecular targeting with clinical utility and therapeutic beneficence.
Collapse
Affiliation(s)
- Manjima Chatterjee
- School of BioSciences and Technology, VIT University, Vellore 632 014, India
| | | |
Collapse
|