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1
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Powrózek T, Otieno MO, Maffeo D, Frullanti E, Martinez-Useros J. Blood circulating miRNAs as pancreatic cancer biomarkers: An evidence from pooled analysis and bioinformatics study. Int J Biol Macromol 2025:142469. [PMID: 40180095 DOI: 10.1016/j.ijbiomac.2025.142469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 03/09/2025] [Accepted: 03/22/2025] [Indexed: 04/05/2025]
Abstract
Pancreatic cancer (PC) is one of the deadliest cancers, characterized by a poor prognosis. Currently, there are no screening programs for the early detection of PC, and existing diagnostic methods are primarily limited to high-risk individuals. Biomarkers such as CA19-9 have not significantly improved early diagnosis, making the identification of new potential biomarkers crucial for routine clinical practice. Among the candidate biomarkers, miRNAs have been most extensively studied due to their role in regulating gene expression (either as oncomiRs or tumor suppressor miRNAs) and their potential for minimally invasive analysis through liquid biopsy techniques. This review aims to summarize the current literature on blood-circulating miRNAs and their diagnostic value in PC detection, considering the context of CA19-9 and benign pancreatic diseases. The data from the collected studies were curated through both statistical and bioinformatics analyses to identify the most promising miRNAs with optimal diagnostic accuracy for PC detection and to assess their role in the molecular processes leading to tumor development.
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Affiliation(s)
- Tomasz Powrózek
- Department of Human Physiology, Medical University of Lublin, Lublin, Poland.
| | - Michael Ochieng' Otieno
- Translational Oncology Division, Oncohealth Institute, Fundacion Jiménez Díaz University Hospital, Madrid, Spain
| | - Debora Maffeo
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy; Cancer Genomics and Systems Biology Lab, Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Elisa Frullanti
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy; Cancer Genomics and Systems Biology Lab, Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Javier Martinez-Useros
- Translational Oncology Division, Oncohealth Institute, Fundacion Jiménez Díaz University Hospital, Madrid, Spain; Area of Physiology, Department of Basic Health Sciences, Faculty of Health Sciences, Rey Juan Carlos University, Madrid, Spain
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2
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Yang J, Lin N, Niu M, Yin B. Circulating tumor DNA mutation analysis: advances in its application for early diagnosis of hepatocellular carcinoma and therapeutic efficacy monitoring. Aging (Albany NY) 2024; 16:11460-11474. [PMID: 39033781 PMCID: PMC11315387 DOI: 10.18632/aging.205980] [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: 01/19/2024] [Accepted: 05/21/2024] [Indexed: 07/23/2024]
Abstract
In recent years, the detection and analysis of circulating tumor DNA (ctDNA) have emerged as a new focus in the field of cancer research, particularly in the early diagnosis of hepatocellular carcinoma (HCC) and monitoring of therapeutic efficacy. ctDNA, which refers to cell-free DNA fragments released into the bloodstream from tumor cells upon cell death or shedding, carries tumor-specific genetic and epigenetic alterations, thereby providing a non-invasive approach for cancer diagnosis and prognosis. The concentration of ctDNA in the blood is higher compared to that in healthy individuals or other liquid biopsies from early-stage cancers, which is closely associated with the early diagnosis and comprehensive sequencing studies of HCC. Recent studies have indicated that sequential ctDNA analysis in patients receiving primary or adjuvant therapy for HCC can detect treatment resistance and recurrence before visible morphological changes in the tumor, making it a valuable basis for rapid adjustment of treatment strategies. However, this technology is continuously being optimized and improved. Challenges such as enhancing the accuracy of ctDNA sequencing tests, reducing the burden of high-throughput sequencing on a large number of samples, and controlling variables in the assessment of the relationship between ctDNA concentration and tumor burden, need to be addressed. Overall, despite the existing challenges, the examination and analysis of ctDNA have opened up new avenues for early diagnosis and therapeutic efficacy monitoring in hepatocellular carcinoma, expanding the horizons of this field.
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Affiliation(s)
- Jing Yang
- Department of Clinical laboratory, Fourth People’s Hospital of Jinan, Jinan 250031, China
| | - Na Lin
- Department of Clinical laboratory, Fourth People’s Hospital of Jinan, Jinan 250031, China
| | - Miaomiao Niu
- Department of Clinical laboratory, Fourth People’s Hospital of Jinan, Jinan 250031, China
| | - Boshu Yin
- Department of Clinical laboratory, Fourth People’s Hospital of Jinan, Jinan 250031, China
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3
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Gorgani L, Mohammadi M, Najafpour Darzi G, Raoof JB. Metal-organic framework (MOF)-based biosensors for miRNA detection. Talanta 2024; 273:125854. [PMID: 38447342 DOI: 10.1016/j.talanta.2024.125854] [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: 08/22/2023] [Revised: 12/31/2023] [Accepted: 02/28/2024] [Indexed: 03/08/2024]
Abstract
MicroRNAs (miRNAs) play several crucial roles in the physiological and pathological processes of the human body. They are considered as important biomarkers for the diagnosis of various disorders. Thus, rapid, sensitive, selective, and affordable detection of miRNAs is of great importance. However, the small size, low abundance, and highly similar sequences of miRNAs impose major challenges to their accurate detection in biological samples. In recent years, metal-organic frameworks (MOFs) have been applied as promising sensing materials for the fabrication of different biosensors due to their distinctive characteristics, such as high porosity and surface area, tunable pores, outstanding adsorption affinities, and ease of functionalization. In this review, the applications of MOFs and MOF-derived materials in the fabrication of fluorescence, electrochemical, chemiluminescence, electrochemiluminescent, and photoelectrochemical biosensors for the detection of miRNAs and their detection principle and analytical performance are discussed. This paper attempts to provide readers with a comprehensive knowledge of the fabrication and sensing mechanisms of miRNA detection platforms.
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Affiliation(s)
- Leila Gorgani
- Biotechnology Research Laboratory, Faculty of Chemical Engineering, Babol Noshirvani University of Technology, Babol, 47148-71167, Iran
| | - Maedeh Mohammadi
- Biotechnology Research Laboratory, Faculty of Chemical Engineering, Babol Noshirvani University of Technology, Babol, 47148-71167, Iran; School of Chemical Engineering, Universiti Sains Malaysia, 14300, Nibong Tebal, Pulau Pinang, Malaysia.
| | - Ghasem Najafpour Darzi
- Biotechnology Research Laboratory, Faculty of Chemical Engineering, Babol Noshirvani University of Technology, Babol, 47148-71167, Iran
| | - Jahan Bakhsh Raoof
- Electroanalytical Chemistry Research Laboratory, Department of Analytical Chemistry, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran
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4
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Li J, Lv M, Huang Q, Hu R, Zhong X, Sun X, Feng W, Han Z, Ma M, Zhang W, Zhou X. FAT4 expression in peripheral blood mononuclear cells is associated with prognosis and immune cell infiltration in hepatocellular carcinoma. Sci Rep 2023; 13:15735. [PMID: 37735184 PMCID: PMC10514079 DOI: 10.1038/s41598-023-42560-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 09/12/2023] [Indexed: 09/23/2023] Open
Abstract
Peripheral blood mononuclear cell (PBMC) genes reflect the host immune status and could be suitable for evaluating the prognosis of patients with hepatocellular carcinoma (HCC), for which a reliable biomarker is unavailable and the host immune responses to cancer cells. This study aimed to investigate prognostically relevant genes in HCC PBMCs and assessed whether their expression represents tumor immune infiltration. Gene expression in PBMCs from patients with advanced or terminal HCC who had survived or died was examined. Correlations among FAT atypical cadherin 4 (FAT4) expression, cancer immune characteristics, and infiltrated immune cell gene marker sets were analyzed. FAT4 expression was lower in the PBMCs of patients with advanced or terminal HCC who had died than that in patients who survived. Kaplan-Meier analysis indicated that FAT4 downregulation was associated with a relatively poor prognosis while overexpression was positively correlated with immune cell infiltration, several immune cell markers, and immune checkpoint expression. Hsa-miR-93-5p represented the most probable upstream microRNA of FAT4. Thus, upregulated FAT4 in PBMCs and HCC tissues might indicate a favorable prognosis and increased immune cell infiltration, while miRNA-93-5p could be a modulator of FAT4 expression. Collectively, these findings suggest novel immunotherapy targets for HCC.
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Affiliation(s)
- Jing Li
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, People's Republic of China
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, People's Republic of China
- Faculty of Chinese Medicine, Taipa, Macau University of Science and Technology, Macao, People's Republic of China
| | - Minling Lv
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, People's Republic of China
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, People's Republic of China
| | - Qi Huang
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, People's Republic of China
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, People's Republic of China
| | - Rui Hu
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, People's Republic of China
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, People's Republic of China
- Faculty of Chinese Medicine, Taipa, Macau University of Science and Technology, Macao, People's Republic of China
| | - Xin Zhong
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, People's Republic of China
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, People's Republic of China
| | - Xinfeng Sun
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, People's Republic of China
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, People's Republic of China
| | - Wenxing Feng
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, People's Republic of China
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, People's Republic of China
| | - Zhiyi Han
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, People's Republic of China
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, People's Republic of China
| | - MengQing Ma
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, People's Republic of China
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, People's Republic of China
| | - Wei Zhang
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, People's Republic of China
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, People's Republic of China
| | - Xiaozhou Zhou
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, People's Republic of China.
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, People's Republic of China.
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5
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Genc S, Yagci T, Vageli DP, Dundar R, Doukas PG, Doukas SG, Tolia M, Chatzakis N, Tsatsakis A, Taghizadehghalehjoughi A. Exosomal MicroRNA-223, MicroRNA-146, and MicroRNA-21 Profiles and Biochemical Changes in Laryngeal Cancer. ACS Pharmacol Transl Sci 2023; 6:820-828. [PMID: 37200807 PMCID: PMC10186621 DOI: 10.1021/acsptsci.3c00038] [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: 02/23/2023] [Indexed: 05/20/2023]
Abstract
Laryngeal squamous cell carcinoma (LSCC) is one of the most aggressive cancers, and its early diagnosis is urgent. Exosomes are believed to have diagnostic significance in cancer. However, the role of serum exosomal microRNAs, miR-223, miR-146, and miR-21, and phosphatase and tensin homologue (PTEN) and hemoglobin subunit delta (HBD) mRNAs in LSCC is unclear. Exosomes were isolated from the blood serum of 10 LSCC patients and 10 healthy controls to perform scanning electron microscopy and liquid chromatography quadrupole time-of-flight mass spectrometry analyses to characterize them and to undergo reverse transcription polymerase chain reaction to identify miR-223, miR-146, miR-21, and PTEN and HBD mRNA expression phenotypes. Biochemical parameters, including serum C-reactive protein (CRP) and vitamin B12, were also obtained. Serum exosomes of 10-140 nm were isolated from LSCC and controls. Serum exosomal miR-223, miR-146, and PTEN were found to be significantly decreased (p < 0.05), in contrast to serum exosomal miRNA-21 (p < 0.01), and serum vitamin B12 and CRP (p < 0.05) were found to be significantly increased, in LSCC vs controls. Our novel data show that the combination of reduced serum exosomal miR-223, miR-146, and miR-21 profiles and biochemical alterations in CRP and vitamin B12 levels may be useful indicators of LSCC that could be validated by large studies. Our findings also suggest a possible negative regulatory effect of miR-21 on PTEN in LSCC, encouraging a more extensive investigation of its role.
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Affiliation(s)
- Sidika Genc
- Faculty
of Medicine, Department of Medical Pharmacology, Bilecik Seyh Edebali University, Bilecik 11230, Turkey
| | - Tarik Yagci
- Faculty
of Medicine, Department of ENT, Bilecik
Seyh Edebali University, Bilecik 11230, Turkey
| | - Dimitra P. Vageli
- Yale
Larynx Laboratory, Department of Surgery (Otolaryngology), Yale School of Medicine, New Haven, Connecticut 06510, United States
| | - Riza Dundar
- Faculty
of Medicine, Department of ENT, Bilecik
Seyh Edebali University, Bilecik 11230, Turkey
| | - Panagiotis G. Doukas
- Yale
Larynx Laboratory, Department of Surgery (Otolaryngology), Yale School of Medicine, New Haven, Connecticut 06510, United States
| | - Sotirios G. Doukas
- Department
of Internal Medicine, Division of Gastroenterology and Hepatology, Saint Peter University Hospital, New Brunswick New Jersey 08901-1780, United States
- Department
of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Maria Tolia
- Department
of Radiology, Faculty of Medicine, University
of Crete, 71003 Heraklion, Greece
| | - Nikolaos Chatzakis
- Otorhinolaryngologist
Consultant, ENT Department of University
Hospital of Crete, 71003 Heraklion, Greece
| | - Aristidis Tsatsakis
- Department
of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Ali Taghizadehghalehjoughi
- Faculty
of Medicine, Department of Medical Pharmacology, Bilecik Seyh Edebali University, Bilecik 11230, Turkey
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6
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Chen Q, Deng Q, Pan Y, Ding X, Liu J. Hypoxia-induced miR-653 enhances colorectal cancer progression by targeting circSETD3/KLF6 axis. J Cancer 2023; 14:163-173. [PMID: 36605481 PMCID: PMC9809325 DOI: 10.7150/jca.78865] [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: 09/12/2022] [Accepted: 12/03/2022] [Indexed: 01/04/2023] Open
Abstract
The present work focused on exploring the role and underlying molecular mechanism of action of the non-coding RNA (miRNA/circRNA) in colorectal cancer (CRC). Here, we found that miR-653 was dramatically upregulated in CRC tissues and cells. CRC Patients with high miR-653 level possessed poor prognosis. miR-653 elevated proliferation, migration, and invasion, meanwhile suppressed apoptosis of CRC cells. Furthermore, circSETD3 directly sponged miR-653 and negatively regulate miR-653 to affect proliferation, migration, invasion, and apoptosis of CRC cells. Moreover, miR-653 served as carcinoma-promoting gene via targeting KLF6, and circSETD3 knockdown significantly reversed the inhibitory effect of KLF6 overexpression on CRC cells. In addition, hypoxia obviously increased expression of miR-653. Knockdown of miR-653 decreased the effects of hypoxia on CRC cell proliferation, migration and invasion. Taken together, these findings indicated that circSETD3/miR-653/KLF6 axis may be an effective therapeutic target for CRC patients.
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Affiliation(s)
- Qian Chen
- Department of Gastroenterology, Wuhan Fourth Hospital, Wuhan 430033, China
| | - Qingchun Deng
- Department of Gynecology, The Second Affiliated Hospital of Hainan Medical University, Haikou 570216, China
| | - Yinglian Pan
- Department of Medical Oncology, The First Affiliated Hospital of Hainan Medical University, Haikou, 570102, China
| | - Xiangwu Ding
- Department of Gastroenterology, Wuhan Fourth Hospital, Wuhan 430033, China
| | - Jing Liu
- Department of Neurology, Wuhan Fourth Hospital, Wuhan 430033, China.,✉ Corresponding author: Jing Liu, E-mail:
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7
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Serum microRNAs as new criteria for referral to early palliative care services in treatment-naïve advanced cancer patients. Oncotarget 2022; 13:1341-1349. [PMID: 36528878 PMCID: PMC9760266 DOI: 10.18632/oncotarget.28327] [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] [Indexed: 12/23/2022] Open
Abstract
A major obstacle to the implementation of early palliative care (EPC) is the lack of objective criteria for referral to EPC. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers. The present study investigated objective definitions for referral to EPC using microRNA. A total of 178 serum samples were obtained from patients with lung, gastrointestinal, colorectal, bile duct, pancreas and bladder cancers who were treatment-naïve and received chemotherapy between January 2011 and December 2013 at National Cancer Center Hospital East. We investigated expression levels of miRNAs using microarrays. The primary outcome was prediction of admission to a palliative care unit ≤6 months after first visit. Diagnostic models using clinical characteristics, miRNAs and combinations of both were constructed. The miRNA models were constructed using 6 miRNA levels. The best areas under the receiver operating characteristic curve (AUCs) of the clinical model was 0.741, while the average AUCs of miRNA-based models and combination models were 0.769 and 0.806, respectively. Combination models showed higher AUCs than the clinical model (p < 0.023). The present combination models might offer new objective definitions for referral to EPC and thus contribute to real-world implementation of EPC.
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Circulating MicroRNA-122 as a Potential Biomarker for Hepatitis C Virus Induced Hepatocellular Carcinoma. INTERNATIONAL JOURNAL OF CANCER MANAGEMENT 2022. [DOI: 10.5812/ijcm-131221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
Abstract
Background: The microRNA (miRNA) mediated translational repression can cause various diseases in humans. The liver-specific miRNA (microRNA-122 (miR-122)) is primarily involved in tissue tropism during hepatitis C virus (HCV) infection which ultimately leads to hepatocellular carcinoma (HCC). Objectives: This study focuses on evaluating host serum miR-122 as a prognostic marker in HCV-induced hepatocellular carcinoma. Methods: Evaluation of miR-122 expression was carried out by quantitative real time PCR. Results: Positive expression of miR-122 was observed in patients with chronic hepatitis C (CHC) followed by HCC patients compared to healthy controls. A difference in median levels of the miR-122 expression in CHC and HCC patients (P < 0.000) was found in contrast to cirrhosis patients (P = 0.511). The serum miR-122 expression was found threefold higher in liver cirrhosis patients than chronic hepatitis. Further, the area under the receiver operating characteristic curve (AUROC) analysis of miR-122 expression profile can efficiently distinguish CHC patients (AUROC = 0.978, P = 0.000, 95% confidence interval (CI) = 0.958 to 0.998) and HCC from healthy controls (AUROC = 0.971, P = 0.000, 95% CI = 0.944 to 0.997). Moreover, receiver operating characteristic (ROC) curve analysis significantly distinguished between CHC patients from cirrhosis patients (AUROC = 0.955, P = 0.000, 95% CI = 0.925 to 0.986) but not CHC from HCC patients (AUROC = 0.584, P = 0.104, 95% CI = 0.485 to 0.684). This study revealed a substantial correlation of miR-122 with HCV viral load (r = 0.56, P = 0.000), ALT (r = 0.67, P = 0.000) and AST (r = 0.65, P = 0.000) levels. Conclusions: Serum miR-122 can potentially serve as a promising prognostic tool for HCV induced HCC.
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9
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Yang JC, Hu JJ, Li YX, Luo W, Liu JZ, Ye DW. Clinical Applications of Liquid Biopsy in Hepatocellular Carcinoma. Front Oncol 2022; 12:781820. [PMID: 35211399 PMCID: PMC8860830 DOI: 10.3389/fonc.2022.781820] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 01/04/2022] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and poor prognosis in the world. The low rate of early diagnosis, as well as the high risk of postoperative metastasis and recurrence, led to the poor clinical prognosis of HCC patients. Currently, it mainly depends on serum markers, imaging examination, and tissue biopsy to diagnose and determine the recurrence and metastasis of HCC after treatments. Nevertheless, the accuracy and sensitivity of serum markers and imaging for early HCC diagnosis are suboptimal. Tissue biopsy, containing limited tissue samples, is insufficient to reveal comprehensive tumor biology information and is inappropriate to monitor dynamic tumor progression due to its invasiveness. Thus, low invasive diagnostic methods and novel biomarkers with high sensitivity and reliability must be found to improve HCC detection and prediction. As a non-invasive, dynamic, and repeatable detection method, “liquid biopsy”, has attracted much attention to early diagnosis and monitoring of treatment response, which promotes the progress of precision medicine. This review summarizes the clinical applications of liquid biopsy in HCC, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosome in early diagnosis, prognostic evaluation, disease monitoring, and guiding personalized treatment.
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Affiliation(s)
- Jin-Cui Yang
- Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun-Jie Hu
- Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yi-Xin Li
- Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Luo
- Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jin-Zhou Liu
- Department of Pain Management, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Da-Wei Ye
- Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Department of Pancreatic-Biliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
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10
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Natarelli L, Virgili F, Weber C. SARS-CoV-2, Cardiovascular Diseases, and Noncoding RNAs: A Connected Triad. Int J Mol Sci 2021; 22:12243. [PMID: 34830125 PMCID: PMC8620514 DOI: 10.3390/ijms222212243] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 11/10/2021] [Accepted: 11/11/2021] [Indexed: 12/23/2022] Open
Abstract
Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is characterized by important respiratory impairments frequently associated with severe cardiovascular damages. Moreover, patients with pre-existing comorbidity for cardiovascular diseases (CVD) often present a dramatic increase in inflammatory cytokines release, which increases the severity and adverse outcomes of the infection and, finally, mortality risk. Despite this evident association at the clinical level, the mechanisms linking CVD and COVID-19 are still blurry and unresolved. Noncoding RNAs (ncRNAs) are functional RNA molecules transcribed from DNA but usually not translated into proteins. They play an important role in the regulation of gene expression, either in relatively stable conditions or as a response to different stimuli, including viral infection, and are therefore considered a possible important target in the design of specific drugs. In this review, we introduce known associations and interactions between COVID-19 and CVD, discussing the role of ncRNAs within SARS-CoV-2 infection from the perspective of the development of efficient pharmacological tools to treat COVID-19 patients and taking into account the equally dramatic associated consequences, such as those affecting the cardiovascular system.
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Affiliation(s)
- Lucia Natarelli
- Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-Universität (LMU), 800336 Munich, Germany;
| | - Fabio Virgili
- Research Center for Food and Nutrition, Council for Agricultural Research and Economics, 00178 Rome, Italy;
| | - Christian Weber
- Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-Universität (LMU), 800336 Munich, Germany;
- German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, 80336 Munich, Germany
- Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 HX Maastricht, The Netherlands
- Munich Cluster for Systems Neurology (SyNergy), Institute for Stroke and Dementia Research, 81377 Munich, Germany
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11
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Tito C, De Falco E, Rosa P, Iaiza A, Fazi F, Petrozza V, Calogero A. Circulating microRNAs from the Molecular Mechanisms to Clinical Biomarkers: A Focus on the Clear Cell Renal Cell Carcinoma. Genes (Basel) 2021; 12:1154. [PMID: 34440329 PMCID: PMC8391131 DOI: 10.3390/genes12081154] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 07/26/2021] [Accepted: 07/26/2021] [Indexed: 02/06/2023] Open
Abstract
microRNAs (miRNAs) are emerging as relevant molecules in cancer development and progression. MiRNAs add a post-transcriptional level of control to the regulation of gene expression. The deregulation of miRNA expression results in changing the molecular circuitry in which miRNAs are involved, leading to alterations of cell fate determination. In this review, we describe the miRNAs that are emerging as innovative molecular biomarkers from liquid biopsies, not only for diagnosis, but also for post-surgery management in cancer. We focus our attention on renal cell carcinoma, in particular highlighting the crucial role of circulating miRNAs in clear cell renal cell carcinoma (ccRCC) management. In addition, the functional deregulation of miRNA expression in ccRCC is also discussed, to underline the contribution of miRNAs to ccRCC development and progression, which may be relevant for the identification and design of innovative clinical strategies against this tumor.
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Affiliation(s)
- Claudia Tito
- Department of Anatomical, Histological, Forensic & Orthopedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy; (C.T.); (A.I.); (F.F.)
| | - Elena De Falco
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy; (E.D.F.); (P.R.); (V.P.)
- Mediterranea Cardiocentro, 80122 Naples, Italy
| | - Paolo Rosa
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy; (E.D.F.); (P.R.); (V.P.)
| | - Alessia Iaiza
- Department of Anatomical, Histological, Forensic & Orthopedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy; (C.T.); (A.I.); (F.F.)
| | - Francesco Fazi
- Department of Anatomical, Histological, Forensic & Orthopedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy; (C.T.); (A.I.); (F.F.)
| | - Vincenzo Petrozza
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy; (E.D.F.); (P.R.); (V.P.)
| | - Antonella Calogero
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy; (E.D.F.); (P.R.); (V.P.)
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Mazziotta C, Lanzillotti C, Iaquinta MR, Taraballi F, Torreggiani E, Rotondo JC, Otòn-Gonzalez L, Mazzoni E, Frontini F, Bononi I, De Mattei M, Tognon M, Martini F. MicroRNAs Modulate Signaling Pathways in Osteogenic Differentiation of Mesenchymal Stem Cells. Int J Mol Sci 2021; 22:2362. [PMID: 33673409 PMCID: PMC7956574 DOI: 10.3390/ijms22052362] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/18/2021] [Accepted: 02/24/2021] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cells (MSCs) have been identified in many adult tissues and they have been closely studied in recent years, especially in view of their potential use for treating diseases and damaged tissues and organs. MSCs are capable of self-replication and differentiation into osteoblasts and are considered an important source of cells in tissue engineering for bone regeneration. Several epigenetic factors are believed to play a role in the osteogenic differentiation of MSCs, including microRNAs (miRNAs). MiRNAs are small, single-stranded, non-coding RNAs of approximately 22 nucleotides that are able to regulate cell proliferation, differentiation and apoptosis by binding the 3' untranslated region (3'-UTR) of target mRNAs, which can be subsequently degraded or translationally silenced. MiRNAs control gene expression in osteogenic differentiation by regulating two crucial signaling cascades in osteogenesis: the transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP) and the Wingless/Int-1(Wnt)/β-catenin signaling pathways. This review provides an overview of the miRNAs involved in osteogenic differentiation and how these miRNAs could regulate the expression of target genes.
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Affiliation(s)
- Chiara Mazziotta
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Carmen Lanzillotti
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Maria Rosa Iaquinta
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Francesca Taraballi
- Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX 77030, USA;
- Orthopedics and Sports Medicine, Houston Methodist Hospital, 6565 Fannin Street, Houston, TX 77030, USA
| | - Elena Torreggiani
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - John Charles Rotondo
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Lucia Otòn-Gonzalez
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Elisa Mazzoni
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Francesca Frontini
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Ilaria Bononi
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Monica De Mattei
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Mauro Tognon
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
| | - Fernanda Martini
- Department of Medical Sciences, Section of Experimental Medicine, School of Medicine, University of Ferrara, 64b Fossato di Mortara Street, 44121 Ferrara, Italy; (C.M.); (C.L.); (M.R.I.); (E.T.); (J.C.R.); (L.O.-G.); (E.M.); (F.F.); (I.B.); (F.M.)
- Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 70, Eliporto Street, 44121 Ferrara, Italy
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Effects of miRNA-140 on the Growth and Clinical Prognosis of SMMC-7721 Hepatocellular Carcinoma Cell Line. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6638915. [PMID: 33628799 PMCID: PMC7884124 DOI: 10.1155/2021/6638915] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 12/27/2020] [Accepted: 01/07/2021] [Indexed: 12/15/2022]
Abstract
Background A growing number of studies have suggested that microRNAs exert an essential role in the development and occurrence of multiple tumours and act as crucial regulators in various biological processes. However, the expression and function of miRNA-140 in hepatocellular carcinoma (HCC) cells are not yet adequately identified and manifested. Methods The expression of miRNA-140 was determined in HCC tissues and adjacent nontumour tissues by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival analysis and Cox regression analysis were performed to explore the correlation between miRNA-140 expression level and the survival rate of patients with HCC. Additionally, overexpression experiments were conducted to investigate the biological role of miRNA-140 in HCC cells. Bioinformatics was used to predict the related target genes and pathways of miRNA-140. Results QRT-PCR results signified that the expression level of miRNA-140 in HCC was lower than that of adjacent normal tissues (P < 0.0001). Compared with the control group, the SMMC-7721 HCC cells in the miRNA-140 mimic group had a decrease in proliferation, migration, and invasion (P < 0.05), whereas those in the miRNA-140 inhibitor group had an increase in proliferation, migration, and invasion (P < 0.05). Cell cycle arrest occurred in the G0/1 phase. Prognosis analysis showed that the expression level of miRNA-140 was not related to the prognosis of HCC. Furthermore, the Kaplan-Meier test revealed that patients with lower miRNA-140 expression levels in liver cancer tissue had significantly shorter disease-free survival (DFS, P = 0.004) and overall survival (OS) times (P = 0.010) after hepatectomy. Cox regression analysis further indicated that miRNA-140 was an independent risk factor that may affect the DFS (P = 0.004) and OS times (P = 0.014) of patients after hepatectomy. Our results suggested that miRNA-140 might be a crucial regulator involved in the HCC progression and is thus considered a potential prognostic biomarker and therapeutic target for HCC.
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Fawzy MS, Toraih EA. MicroRNA signatures as predictive biomarkers in transarterial chemoembolization‐treated hepatocellular carcinoma. PRECISION MEDICAL SCIENCES 2021. [DOI: 10.1002/prm2.12031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Affiliation(s)
- Manal S. Fawzy
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine Suez Canal University Ismailia Egypt
- Biochemistry Department, Faculty of Medicine Northern Border University Arar KSA
| | - Eman A. Toraih
- Department of Surgery Tulane University, School of Medicine New Orleans Louisiana USA
- Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine Suez Canal University Ismailia Egypt
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15
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Jiao Y, Xu P, Shi H, Chen D, Shi H. Advances on liver cell-derived exosomes in liver diseases. J Cell Mol Med 2020; 25:15-26. [PMID: 33247543 PMCID: PMC7810930 DOI: 10.1111/jcmm.16123] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 11/02/2020] [Accepted: 11/06/2020] [Indexed: 12/12/2022] Open
Abstract
Exosomes are extracellular vesicles with diameters ranging from 30 to 150 nm, which contain several donor cell‐associated proteins as well as mRNA, miRNA, and lipids and coordinate multiple physiological and pathological functions through horizontal communication between cells. Almost all types of liver cells, such as hepatocytes and Kupffer cells, are exosome‐releasing and/or exosome‐targeted cells. Exosomes secreted by liver cells play an important role in regulating general physiological functions and also participate in the onset and development of liver diseases, including liver cancer, liver injury, liver fibrosis and viral hepatitis. Liver cell‐derived exosomes carry liver cell‐specific proteins and miRNAs, which can be used as diagnostic biomarkers and treatment targets of liver disease. This review discusses the functions of exosomes derived from different liver cells and provides novel insights based on the latest developments regarding the roles of exosomes in the diagnosis and treatment of liver diseases.
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Affiliation(s)
- Yan Jiao
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer, Beijing, China
| | - Ping Xu
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer, Beijing, China
| | - Honglin Shi
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer, Beijing, China
| | - Dexi Chen
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer, Beijing, China
| | - Hongbo Shi
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer, Beijing, China
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16
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Li K, Zhang Q, Niu D, Xing H. Mining miRNAs' Expressions in Glioma Based on GEO Database and Their Effects on Biological Functions. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5637864. [PMID: 33102581 PMCID: PMC7576330 DOI: 10.1155/2020/5637864] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 06/04/2020] [Indexed: 12/13/2022]
Abstract
PURPOSE To mine miR expression in glioma based on the Gene Expression Omnibus (GEO) database and to explore its effects on biological functions. METHODS Differentially expressed miRs in glioma-related chips were found out based on the GEO database. Fifty patients with glioma treated in our hospital from February 2012 to July 2013 (observation group, OG) and a further 50 healthy people undergoing physical examinations (control group, CG) were enrolled. miR-873-5p expression in serum and in U87, T98G, U251, LN-229, and HEK-293T cells was tested by qRT-PCR. T98G and U251 cells were transfected with miR-873-5p-mimics and miR-NC sequences. The expression in the two cells was also tested by qRT-PCR. The proliferation, invasion, and apoptosis of the transfected cells were, respectively, tested by MTT assay, Transwell, and flow cytometry. The patients were followed up for 5 years to observe their survival. RESULTS miR-873-5p expression in OG was remarkably higher than that in CG (p < 0.001). miR-873-5p was closely correlated with the tumor diameter, lymph node metastasis, and TNM staging of the patients (p < 0.05). According to the plotted receiver operating characteristic (ROC) curves, the areas under the curves (AUCs) of miR-873-5p for diagnosing the disease, tumor diameter, lymph node metastasis, and TNM staging were 0.842, 0.706, 0.865, and 0.793, respectively. The 5-year and recurrence-free survival rates in the low expression group were lower than those in the high expression group. According to multivariate Cox regression analysis, tumor diameter, lymph node metastasis, and miR-873-5p were independent prognostic factors for the disease. After transfection, compared with those in the miR-NC group, T98G and U251 cells in the miR-873-5p-mimic group had remarkably higher miR-873-5p expression (p < 0.05), remarkably lower proliferation and invasion rates (p < 0.05), and a remarkably higher apoptotic rate (p < 0.05). CONCLUSIONS miR-873-5p can inhibit glioma cells to proliferate and invade, and promote their apoptosis, so it is expected to become a potential diagnostic index and therapeutic target for glioma.
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Affiliation(s)
- Ke Li
- Department of Neurosurgery, Binzhou Medical University Hospital, Binzhou 256603, China
| | - Qi Zhang
- Department of Neurosurgery, Binzhou Medical University Hospital, Binzhou 256603, China
| | - Duan Niu
- Department of Pediatrics, Binchengqu Shili Hospital, Binzhou 256600, China
| | - Hailong Xing
- Department of Neurosurgery, Binzhou Medical University Hospital, Binzhou 256603, China
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Clinicopathological significance of miR-27b targeting Golgi protein 73 in patients with hepatocellular carcinoma. Anticancer Drugs 2020; 30:186-194. [PMID: 30418194 DOI: 10.1097/cad.0000000000000711] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Using five bioinformatics analysis software, we identified Golgi protein 73 (GP73) as a putative target of microRNA-27b (miR-27b), which is closely related to various biological processes or diseases such as bone metabolism disease, adipose cell and muscle cell development, pulmonary hypertension, cervical cancer, and breast cancer. However, the clinical significance of miR-27b in hepatocellular carcinoma (HCC) is still unclear. The differential expression of miR-27b in HCC and adjacent normal liver tissues was measured by quantitative reverse transcription PCR. Our results showed that the expression of miR-27b in tumor tissues is lower than that in adjacent nontumor tissues. The expression of miR-27b was significantly lower in HCC tissues with high expression of GP73, when compared with adjacent nontumor tissues. Moreover, down-regulated expression of miR-27b was closely correlated with serum GP73, tumor-node-metastasis stage, tumor size, and portal vein thrombosis. GP73 mRNA might be a target of miR-27b. The 5-year overall survival rate of the low miR-27b expression group was significantly lower than that of the high miR-27b expression group. Moreover, multivariate analysis of prognostic factors, with a Cox proportional hazards model, showed that low miR-27b expression was a significant and independent predictor of poor survival in HCC. Hence, the abnormal expression of miR-27b might be related to the occurrence and development of tumors. Similarly, a study in the Cancer Genome Atlas database demonstrated that the expression of miR-27b in 50 normal individuals was 1.6 times higher than that of 372 patients with liver cancer. The overall survival rate of the low GP73 expression group (275 liver cancer patients) was significantly longer than that of the high GP73 expression group (90 normal individuals). MiR-27b suppresses the expression of GP73 and is therefore a potential prognostic biomarker and therapy target in HCC.
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Xu J, An P, Winkler CA, Yu Y. Dysregulated microRNAs in Hepatitis B Virus-Related Hepatocellular Carcinoma: Potential as Biomarkers and Therapeutic Targets. Front Oncol 2020; 10:1271. [PMID: 32850386 PMCID: PMC7399632 DOI: 10.3389/fonc.2020.01271] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 06/19/2020] [Indexed: 12/12/2022] Open
Abstract
MicroRNAs (miRNAs) are non-coding small RNAs that can function as gene regulators and are involved in tumorigenesis. We review the commonly dysregulated miRNAs in liver tumor tissues and plasma/serum of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. The frequently reported up-regulated miRNAs in liver tumor tissues include miR-18a, miR-21, miR-221, miR-222, and miR-224, whereas down-regulated miRNAs include miR-26a, miR-101, miR-122, miR-125b, miR-145, miR-199a, miR-199b, miR-200a, and miR-223. For a subset of these miRNAs (up-regulated miR-222 and miR-224, down-regulated miR-26a and miR-125b), the pattern of dysregulated circulating miRNAs in plasma/serum is mirrored in tumor tissue based on multiple independent studies. Dysregulated miRNAs target oncogenes or tumor suppressor genes involved in hepatocarcinogenesis. Normalization of dysregulated miRNAs by up- or down-regulation has been shown to inhibit HCC cell proliferation or sensitize liver cancer cells to chemotherapeutic treatment. miRNAs hold as yet unrealized potential as biomarkers for early detection of HCC and as precision therapeutic targets, but further studies in diverse populations and across all stages of HCC are needed.
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Affiliation(s)
- Jinghang Xu
- Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Peking University, Beijing, China
- Basic Research Laboratory, Molecular Genetic Epidemiology Section, Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
| | - Ping An
- Basic Research Laboratory, Molecular Genetic Epidemiology Section, Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
| | - Cheryl A. Winkler
- Basic Research Laboratory, Molecular Genetic Epidemiology Section, Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
| | - Yanyan Yu
- Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Peking University, Beijing, China
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Qu S, Shi Q, Xu J, Yi W, Fan H. Weighted Gene Coexpression Network Analysis Reveals the Dynamic Transcriptome Regulation and Prognostic Biomarkers of Hepatocellular Carcinoma. Evol Bioinform Online 2020; 16:1176934320920562. [PMID: 32523331 PMCID: PMC7235675 DOI: 10.1177/1176934320920562] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 03/30/2020] [Indexed: 12/14/2022] Open
Abstract
This study was aimed at revealing the dynamic regulation of mRNAs, long noncoding RNAs (lncRNAs), and microRNAs (miRNAs) in hepatocellular carcinoma (HCC) and to identify HCC biomarkers capable of predicting prognosis. Differentially expressed mRNAs (DEmRNAs), lncRNAs, and miRNAs were acquired by comparing expression profiles of HCC with normal samples, using an expression data set from The Cancer Genome Atlas. Altered biological functions and pathways in HCC were analyzed by subjecting DEmRNAs to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Gene modules significantly associated with disease status were identified by weighted gene coexpression network analysis. An lncRNA-mRNA and an miRNA-mRNA coexpression network were constructed for genes in disease-related modules, followed by the identification of prognostic biomarkers using Kaplan-Meier survival analysis. Differential expression and association with the prognosis of 4 miRNAs were verified in independent data sets. A total of 1220 differentially expressed genes were identified between HCC and normal samples. Differentially expressed mRNAs were significantly enriched in functions and pathways related to “plasma membrane structure,” “sensory perception,” “metabolism,” and “cell proliferation.” Two disease-associated gene modules were identified. Among genes in lncRNA-mRNA and miRNA-mRNA coexpression networks, 9 DEmRNAs and 7 DEmiRNAs were identified to be potential prognostic biomarkers. MIMAT0000102, MIMAT0003882, and MIMAT0004677 were successfully validated in independent data sets. Our results may advance our understanding of molecular mechanisms underlying HCC. The biomarkers may contribute to diagnosis in future clinical practice.
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Affiliation(s)
- Shuping Qu
- Department of Hepatic Surgery, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Qiuyuan Shi
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jing Xu
- Department of Interventional Oncology, Shanghai Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wanwan Yi
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Hengwei Fan
- Department of Hepatic Surgery, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
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Iacob DG, Rosca A, Ruta SM. Circulating microRNAs as non-invasive biomarkers for hepatitis B virus liver fibrosis. World J Gastroenterol 2020; 26:1113-1127. [PMID: 32231417 PMCID: PMC7093315 DOI: 10.3748/wjg.v26.i11.1113] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 03/04/2020] [Accepted: 03/09/2020] [Indexed: 02/06/2023] Open
Abstract
Viruses can alter the expression of host microRNAs (MiRNA s) and modulate the immune response during a persistent infection. The dysregulation of host MiRNA s by hepatitis B virus (HBV) contributes to the proinflammatory and profibrotic changes within the liver. Multiple studies have documented the differential regulation of intracellular and circulating MiRNA s during different stages of HBV infection. Circulating MiRNA s found in plasma and/or extracellular vesicles can integrate data on viral-host interactions and on the associated liver injury. Hence, the detection of circulating MiRNA s in chronic HBV hepatitis could offer a promising alternative to liver biopsy, as their expression is associated with HBV replication, the progression of liver fibrosis, and the outcome of antiviral treatment. The current review explores the available data on miRNA involvement in HBV pathogenesis with an emphasis on their potential use as biomarkers for liver fibrosis.
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Affiliation(s)
- Diana Gabriela Iacob
- Infectious Diseases Department, "Carol Davila" University of Medicine and Pharmacy, Bucharest 050474, Romania
- Bucharest Emergency University Hospital, Bucharest 050098, Romania
| | - Adelina Rosca
- Virology Department, Carol Davila University of Medicine and Pharmacy, Bucharest 050474, Romania
- Viral Emerging Diseases Department, Ștefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Simona Maria Ruta
- Virology Department, Carol Davila University of Medicine and Pharmacy, Bucharest 050474, Romania
- Viral Emerging Diseases Department, Ștefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
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Abstract
Abdominal tumors (AT) in children account for approximately 17% of all pediatric solid tumor cases, and frequently exhibit embryonal histological features that differentiate them from adult cancers. Current molecular approaches have greatly improved the understanding of the distinctive pathology of each tumor type and enabled the characterization of novel tumor biomarkers. As seen in abdominal adult tumors, microRNAs (miRNAs) have been increasingly implicated in either the initiation or progression of childhood cancer. Moreover, besides predicting patient prognosis, they represent valuable diagnostic tools that may also assist the surveillance of tumor behavior and treatment response, as well as the identification of the primary metastatic sites. Thus, the present study was undertaken to compile up-to-date information regarding the role of dysregulated miRNAs in the most common histological variants of AT, including neuroblastoma, nephroblastoma, hepatoblastoma, hepatocarcinoma, and adrenal tumors. Additionally, the clinical implications of dysregulated miRNAs as potential diagnostic tools or indicators of prognosis were evaluated.
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22
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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: 374] [Impact Index Per Article: 74.8] [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.
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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.
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Ziogas IA, Sioutas G, Mylonas KS, Tsoulfas G. Role of MicroRNA in the Diagnosis and Management of Hepatocellular Carcinoma. Microrna 2020; 9:25-40. [PMID: 31218966 DOI: 10.2174/2211536608666190619155406] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 03/11/2019] [Accepted: 05/06/2019] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors in the world and comes third in cancer-induced mortality. The need for improved and more specific diagnostic methods that can detect early-stage disease is immense, as it is amenable to curative modalities, while advanced HCC is associated with low survival rates. microRNA (miRNA) expression is deregulated in HCC and this can be implemented both diagnostically and therapeutically. OBJECTIVE To provide a concise review on the role of miRNA in diagnosis, prognosis, and treatment of HCC. METHODS We conducted a comprehensive review of the PubMed bibliographic database. RESULTS Multiple miRNAs are involved in the pathogenesis of HCC. Measurement of the levels of these miRNAs either in tumor tissue or in the blood constitutes a promising diagnostic, as well as prognostic tool. OncomiRs are miRNAs that promote tumorigenesis, thus inhibiting them by administering antagomiRs is a promising treatment option. Moreover, replacement of the depleted miRNAs is another potential therapeutic approach for HCC. Modification of miRNA levels may also regulate sensitivity to chemotherapeutic agents. CONCLUSION miRNA play a pivotal role in HCC pathogenesis and once the underlying mechanisms are elucidated, they will become part of everyday clinical practice against HCC.
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Affiliation(s)
- Ioannis A Ziogas
- Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
- Surgery Working Group, Society of Junior Doctors, Athens, Greece
| | - Georgios Sioutas
- Surgery Working Group, Society of Junior Doctors, Athens, Greece
- Medical School, Democritus University of Thrace, Alexandroupolis, Greece
| | - Konstantinos S Mylonas
- Surgery Working Group, Society of Junior Doctors, Athens, Greece
- Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Tsoulfas
- 1st Department of Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Han B, Huang J, Yang Z, Zhang J, Wang X, Xu N, Meng H, Wu J, Huang Q, Yang X, Shen R, Sun C. miR-449a Is Related to Short-Term Recurrence of Hepatocellular Carcinoma and Inhibits Migration and Invasion by Targeting Notch1. Onco Targets Ther 2019; 12:10975-10987. [PMID: 31853185 PMCID: PMC6916688 DOI: 10.2147/ott.s216997] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Accepted: 11/19/2019] [Indexed: 12/23/2022] Open
Abstract
PURPOSE To explore the effect of miR-449a inhibits migration and invasion by targeting Notch1 and regulating epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC), and further study on the molecular mechanism. PATIENTS AND METHODS The expression of miR-449a and Notch1 in HCC cells and tissues was detected by qRT-PCR. The HCC cell line HCCLM3 and SMMC-7721 were transfected with miR-449a. The invasion and migration of HCC cell lines were detected by transwell assay and wound healing assay. The Notch pathway and EMT related protein were detected with Western Blotting. The specific binding site of mir-449a on notch1 gene was detected by luciferase assay. RESULTS We found the expression of miR-449a was related to short-term recurrence of hepatocellular carcinoma after hepatectomy and acted as independent risk factors of DFS and OS. The expression of miR-449a decreased in tumor tissues and HCC cell lines, but the expression of Notch1 increased. The overexpressed miR-449a promoted the invasiveness in vitro by regulating EMT via Notch pathway. Mechanically, miR-449a inhibited the translation of Notch1 protein by binding to 3' UTR of its mRNA directly. CONCLUSION miR-449a is short-term recurrence-related miRNA and inhibits the invasion and metastasis ability of HCC cells by regulating EMT via Notch pathway. miR-449a may be a new effective therapeutic target for HCC.
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Affiliation(s)
- Bing Han
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao City266003, Shandong Province, People’s Republic of China
- Asian Liver Center, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Jiawei Huang
- Department of Special Medicine, School of Basic Medical College, Qingdao University, Qingdao City266021, Shandong Province, People’s Republic of China
| | - Zhenjie Yang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao City266003, Shandong Province, People’s Republic of China
| | - Jiaqi Zhang
- Department of Special Medicine, School of Basic Medical College, Qingdao University, Qingdao City266021, Shandong Province, People’s Republic of China
| | - Xiaomin Wang
- Department of Special Medicine, School of Basic Medical College, Qingdao University, Qingdao City266021, Shandong Province, People’s Republic of China
| | - Ning Xu
- Department of Special Medicine, School of Basic Medical College, Qingdao University, Qingdao City266021, Shandong Province, People’s Republic of China
| | - Haining Meng
- Department of Special Medicine, School of Basic Medical College, Qingdao University, Qingdao City266021, Shandong Province, People’s Republic of China
| | - Junyu Wu
- Department of Special Medicine, School of Basic Medical College, Qingdao University, Qingdao City266021, Shandong Province, People’s Republic of China
| | - Qiao Huang
- Department of Special Medicine, School of Basic Medical College, Qingdao University, Qingdao City266021, Shandong Province, People’s Republic of China
| | - Xi Yang
- Department of Special Medicine, School of Basic Medical College, Qingdao University, Qingdao City266021, Shandong Province, People’s Republic of China
| | - Ruowu Shen
- Department of Special Medicine, School of Basic Medical College, Qingdao University, Qingdao City266021, Shandong Province, People’s Republic of China
| | - Chuandong Sun
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao City266003, Shandong Province, People’s Republic of China
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Zheng Y, Zhang J, Ye B. miR-138 mediates sorafenib-induced cell survival and is associated with poor prognosis in cholangiocarcinoma cells. Clin Exp Pharmacol Physiol 2019; 47:459-465. [PMID: 31663629 DOI: 10.1111/1440-1681.13205] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 10/22/2019] [Accepted: 10/28/2019] [Indexed: 12/22/2022]
Abstract
Cholangiocarcinoma is an aggressive malignancy with rapid invasion, metastasis and poor prognosis, however, the mechanism mediating its cholangiocarcinoma development needs further investigation. Here, we demonstrate that decreased miR-138 in tumor tissues is related to the poor prognosis in patients, and that miR-138 mediates sorafenib-induced cell survival in cholangiocarcinoma cells. Moreover, miR-138 negatively regulates SOX4 expression by specifically targeting its 3' untranslated region (3' UTR). As per our results, overexpression of SOX4 reversed sorafenib-induced changes in cell viability and apoptosis. Furthermore, the elevated levels of SOX4 in the tumor tissues that correlated with poor prognosis. Overall, the present study reveals that miR-138/SOX4 is involved in sorafinib-mediated cell survival in cholangiocarcinoma cells, and is associated with poor prognosis.
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Affiliation(s)
- Yingjie Zheng
- Department of Gastroenterology, Lianshui County People's Hospital, Huai'an, China
| | - Jingyu Zhang
- Department of Gastroenterology, Lianshui County People's Hospital, Huai'an, China
| | - Bin Ye
- Department of Gastroenterology, Huai'an Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China
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El Mahdy HA, Abdelhamid IA, Amen AI, Abdelsameea E, Hassouna MM. MicroRNA-215 as a Diagnostic Marker in Egyptian Patients with Hepatocellular Carcinoma. Asian Pac J Cancer Prev 2019; 20:2723-2731. [PMID: 31554369 PMCID: PMC6976828 DOI: 10.31557/apjcp.2019.20.9.2723] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Indexed: 12/15/2022] Open
Abstract
Background: MicroRNAs are mentioned as a small non-coding RNAs groups and aberrant miRNA expression was
found in hepatocellular carcinoma (HCC) patients. Aim: To evaluate role of plasma MicroRNA-215 as a diagnostic
tool in HCC patients. Methods: A prospective study included 195 subjects: healthy controls (group I), cirrhotic patients
(group II), and patients with HCC (group III). Clinical examination, radiological and laboratory investigations which
included quantification of miR-215 by Real-time qPCR were done for all cases. Results: Spearman’s rank correlation
revealed that in HCC group, there was a negative correlation between MiRNA-215 and serum AFP levels and focal size
lesion (cm) (rs = -0.72, - 0.94 respectively, p<0.001). Receiver operating characteristics analysis for discrimination
between cirrhosis and HCC groups regarding microRNA-215 displayed 78.3% sensitivity, 88.0% specificity at cutoff
value of ≤ 1.90. Area under the curve (AUC) was 0.87 (p< 0.001). As regards AFP, it had a sensitivity of 81.7%, a
specificity of 66.7 at cutoff value of ≥ 11.50 (ng/mL). Conclusions: Plasma level of miR-215 may be a promising
biomarker in HCC diagnosis. Moreover, if miR-215 combined with AFP, it can be used as a diagnostic biomarker, for
early detection of HCC.
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Affiliation(s)
| | | | | | - Eman Abdelsameea
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Egypt.
| | - Mona M Hassouna
- Department of Clinical pathology, National Liver Institute, Menoufia University, Egypt
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Balaceanu LA. Biomarkers vs imaging in the early detection of hepatocellular carcinoma and prognosis. World J Clin Cases 2019; 7:1367-1382. [PMID: 31363465 PMCID: PMC6656675 DOI: 10.12998/wjcc.v7.i12.1367] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 04/07/2019] [Accepted: 05/03/2019] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the 5th most frequently diagnosed cancer in the world, according to the World Health Organization. The incidence of HCC is between 3/100000 and 78.1/100000, with a high incidence reported in areas with viral hepatitis B and hepatitis C, thus affecting Asia and Africa predominantly. Several international clinical guidelines address HCC diagnosis and are structured according to the geographical area involved. All of these clinical guidelines, however, share a foundation of diagnosis by ultrasound surveillance and contrast imaging techniques, particularly computed tomography, magnetic resonance imaging, and sometimes contrast-enhanced ultrasound. The primary objective of this review was to systematically summarize the recent published studies on the clinical utility of serum biomarkers in the early diagnosis of HCC and for the prognosis of this disease.
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Affiliation(s)
- Lavinia Alice Balaceanu
- Department of Internal Medicine, Carol Davila University of Medicine and Pharmacy, Sf. Ioan Clinical Emergency Hospital, Bucharest 42122, Romania
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28
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Wang Z, Zhu Z, Wang H, Qin B, Liu J, Yao X, Li W, Chen K. Downregulation of circDYNC1H1 exhibits inhibitor effect on cell proliferation and migration in hepatocellular carcinoma through miR‐140‐5p. J Cell Physiol 2019; 234:17775-17785. [PMID: 30864145 DOI: 10.1002/jcp.28403] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 01/15/2019] [Indexed: 12/14/2022]
Affiliation(s)
- Zheng‐Yang Wang
- Department of Pathology The First Affiliated Hospital of Zhengzhou University Zhengzhou China
- Department of Pathology School of Basic Medicine, Zhengzhou University Zhengzhou China
- Henan Key Laboratory for Tumor Pathology Zhengzhou China
| | - Zhu Zhu
- Department of Biological Sample Bank The First Affiliated Hospital of Zhengzhou University Zhengzhou China
| | - Hua‐Fei Wang
- Department of Biological Sample Bank The First Affiliated Hospital of Zhengzhou University Zhengzhou China
| | - Bo Qin
- Department of Translational Medicine Center The First Affiliated Hospital of Zhengzhou University Zhengzhou China
| | - Jing Liu
- Department of Pathology The First Affiliated Hospital of Zhengzhou University Zhengzhou China
- Department of Pathology School of Basic Medicine, Zhengzhou University Zhengzhou China
- Henan Key Laboratory for Tumor Pathology Zhengzhou China
| | - Xiao‐Han Yao
- Department of Medical Research Center The First Affiliated Hospital of Zhengzhou University Zhengzhou China
| | - Wen‐Cai Li
- Department of Pathology The First Affiliated Hospital of Zhengzhou University Zhengzhou China
- Department of Pathology School of Basic Medicine, Zhengzhou University Zhengzhou China
- Henan Key Laboratory for Tumor Pathology Zhengzhou China
| | - Kui‐Sheng Chen
- Department of Pathology The First Affiliated Hospital of Zhengzhou University Zhengzhou China
- Department of Pathology School of Basic Medicine, Zhengzhou University Zhengzhou China
- Henan Key Laboratory for Tumor Pathology Zhengzhou China
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Świtlik WZ, Bielecka-Kowalska A, Karbownik MS, Kordek R, Jabłkowski M, Szemraj J. Forms of diagnostic material as sources of miRNA biomarkers in hepatocellular carcinoma: a preliminary study. Biomark Med 2019; 13:523-534. [PMID: 30854869 DOI: 10.2217/bmm-2018-0485] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Aim: To assess the diagnostic value of selected miRNAs from various material collected from hepatocellular carcinoma (HCC) patients. Patients & methods: Tissue, serum, urine and fecal samples from HCC patients and healthy individuals were screened for associated miRNAs using microarray analysis; the selected miRNAs were then validated by real time-quantitative PCR on 65 patients. Results: Serum miR-122, a combination of serum miR-155 with miR-885-5p, a combination of urinary miR-532-3p with miR-765, and fecal miR-320a displayed 100% efficiency in discriminating patients from controls. A combination of urinary miR-532-3p and miR-765 allowed patients with neoplastic grade G3 to be distinguished from those with G1 and G2. Conclusion: Additionally to serum, urine and feces also appeared to be valuable source of potential HCC noninvasive miRNA biomarkers.
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Affiliation(s)
- Weronika Zofia Świtlik
- Department of Medical Biochemistry, Medical University of Lodz, Mazowiecka Street 6/8 92-215 Lodz, Poland.,Department of Biochemistry, Faculty of Agriculture & Biology, Warsaw University of Life Sciences - SGGW, Nowoursynowska Street 159, 02-776 Warsaw, Poland
| | | | - Michał Seweryn Karbownik
- Department of Pharmacology & Toxicology, Medical University of Lodz, Zeligowskiego Street 7/9, 90-752 Lodz, Poland
| | - Radzisław Kordek
- Department of Pathology Chair of Oncology, Medical University of Lodz, Pomorska Street 251, 92-213 Lodz, Poland
| | - Maciej Jabłkowski
- Department of Infectious & Liver Diseases, Medical University of Lodz, Kniaziewicza Street 1/5, 91-347 Lodz, Poland
| | - Janusz Szemraj
- Department of Medical Biochemistry, Medical University of Lodz, Mazowiecka Street 6/8 92-215 Lodz, Poland.,BioNanoPark Laboratories, Lodz Regional Park of Science & Technologies, Dubois Street 114/116, 93-465, Lodz, Poland
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30
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Sisto R, Capone P, Cerini L, Sanjust F, Paci E, Pigini D, Gatto MP, Gherardi M, Gordiani A, L'Episcopo N, Tranfo G, Chiarella P. Circulating microRNAs as potential biomarkers of occupational exposure to low dose organic solvents. Toxicol Rep 2019; 6:126-135. [PMID: 30671348 PMCID: PMC6330509 DOI: 10.1016/j.toxrep.2019.01.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 01/06/2019] [Accepted: 01/07/2019] [Indexed: 02/07/2023] Open
Abstract
Circulating miRNAs can be used as sensitive biomarkers of low dose exposure to organic solvents at workplace. The miRNA response to organic chemicals elucidates molecular mechanisms occurring after specific occupational exposures. Associations between miRNAs, dose and oxidative stress biomarkers contribute to prevent and promote workers’ health. Circulating microRNAs (miRNAs) have been recently acknowledged as novel and non-invasive biomarkers of exposure to environmental and occupational hazardous substances. This preliminary study investigates the potential role of blood miRNAs as molecular biomarkers of exposure to the most common organic solvents (ethylbenzene, toluene, xylene) used in the shipyard painting activity. Despite the low number of recruited workers, a two-tail standard Students’ test with Holm-Bonferroni adjusted p-value shows a significant up-regulation of two miRNAs (miR_6819_5p and miR_6778_5p) in exposed workers with respect to controls. A correlation analysis between miRNA, differentially expressed in exposed workers and in controls and urinary dose biomarkers i.e. methylhyppuric acid (xylenes metabolite), phenylglyoxylic and mandelic acid (ethylbenzene metabolites) S-benzyl mercapturic acid (toluene metabolite) and S-phenylmercapturic acid (benzene metabolite) measured at the end of the work-shift, allowed the identification of high correlation (0.80-0.99) of specific miRNAs with their respective urinary metabolites. MiRNA_671_5p correlated with methylhippuric, S-phenylmercapturic and S-benzyl mercapturic acid while the miRNA best correlating with the phenylglioxylic acid was miRNA_937_5p. These findings suggest miRNA as sensitive biomarkers of low dose exposure to organic chemicals used at workplace. Urinary DNA and RNA repair biomarkers coming from the oxidation product of guanine have been also associated to the different miRNAs. A significant negative association was found between 8-oxo-7,8-dihydroguanine (8-oxoGua) urinary concentration and miR_6778_5p. The findings of the present pilot study deserve to be tested on a larger population with the perspective of designing a miRNA based test of low dose exposure to organic solvents.
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Affiliation(s)
- Renata Sisto
- INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00078 Monte Porzio Catone, Rome, Italy
| | - Pasquale Capone
- INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00078 Monte Porzio Catone, Rome, Italy
| | - Luigi Cerini
- INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00078 Monte Porzio Catone, Rome, Italy
| | - Filippo Sanjust
- INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00078 Monte Porzio Catone, Rome, Italy
| | - Enrico Paci
- INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00078 Monte Porzio Catone, Rome, Italy
| | - Daniela Pigini
- INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00078 Monte Porzio Catone, Rome, Italy
| | - Maria Pia Gatto
- INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00078 Monte Porzio Catone, Rome, Italy
| | - Monica Gherardi
- INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00078 Monte Porzio Catone, Rome, Italy
| | - Andrea Gordiani
- INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00078 Monte Porzio Catone, Rome, Italy
| | - Nunziata L'Episcopo
- INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00078 Monte Porzio Catone, Rome, Italy
| | - Giovanna Tranfo
- INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00078 Monte Porzio Catone, Rome, Italy
| | - Pieranna Chiarella
- INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00078 Monte Porzio Catone, Rome, Italy
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miR-145 via targeting ERCC2 is involved in arsenite-induced DNA damage in human hepatic cells. Toxicol Lett 2018; 295:220-228. [DOI: 10.1016/j.toxlet.2018.04.028] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2017] [Revised: 04/23/2018] [Accepted: 04/24/2018] [Indexed: 01/06/2023]
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Yu H, Guan Z, Cuk K, Brenner H, Zhang Y. Circulating microRNA biomarkers for lung cancer detection in Western populations. Cancer Med 2018; 7:4849-4862. [PMID: 30259714 PMCID: PMC6198213 DOI: 10.1002/cam4.1782] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Revised: 08/03/2018] [Accepted: 08/14/2018] [Indexed: 12/16/2022] Open
Abstract
Lung cancer (LC) is a leading cause of cancer-related death in the Western world. Patients with LC usually have poor prognosis due to the difficulties in detecting tumors at early stages. Multiple studies have shown that circulating miRNAs might be promising biomarkers for early detection of LC. We aimed to provide an overview of published studies on circulating miRNA markers for early detection of LC and to summarize their diagnostic performance in Western populations. A systematic literature search was performed in PubMed and ISI Web of Knowledge to find relevant studies published up to 11 August 2017. Information on study design, population characteristics, miRNA markers, and diagnostic accuracy (including sensitivity, specificity, and AUC) were independently extracted by two reviewers. Overall, 17 studies evaluating 35 circulating miRNA markers and 19 miRNA panels in serum or plasma were included. The median sensitivity (range) and specificity (range) were, respectively, 78.4% (51.7%-100%) and 78.7% (42.9%-93.5%) for individual miRNAs, and 83.0% (64.0%-100%) and 84.9% (71.0%-100%) for miRNA panels. Most studies incorporated individual miRNA markers as panels (with 2-34 markers), with multiple miRNA-based panels generally outperforming individual markers. Two promising miRNA panels were discovered and verified in prospective cohorts. Of note, both studies exclusively applied miRNA ratios when building up panels. In conclusion, circulating miRNAs may bear potential for noninvasive LC screening, but large studies conducted in screening or longitudinal settings are needed to validate the promising results and optimize the marker panels.
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Affiliation(s)
- Haixin Yu
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Zhong Guan
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Katarina Cuk
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.,Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Yan Zhang
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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Torres-Durán M, Lopez-Campos JL, Barrecheguren M, Miravitlles M, Martinez-Delgado B, Castillo S, Escribano A, Baloira A, Navarro-Garcia MM, Pellicer D, Bañuls L, Magallón M, Casas F, Dasí F. Alpha-1 antitrypsin deficiency: outstanding questions and future directions. Orphanet J Rare Dis 2018; 13:114. [PMID: 29996870 PMCID: PMC6042212 DOI: 10.1186/s13023-018-0856-9] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Accepted: 06/26/2018] [Indexed: 12/14/2022] Open
Abstract
Background Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition that leads to decreased circulating alpha-1 antitrypsin (AAT) levels, significantly increasing the risk of serious lung and/or liver disease in children and adults, in which some aspects remain unresolved. Methods In this review, we summarise and update current knowledge on alpha-1 antitrypsin deficiency in order to identify and discuss areas of controversy and formulate questions that need further research. Results 1) AATD is a highly underdiagnosed condition. Over 120,000 European individuals are estimated to have severe AATD and more than 90% of them are underdiagnosed. Conclusions 2) Several clinical and etiological aspects of the disease are yet to be resolved. New strategies for early detection and biomarkers for patient outcome prediction are needed to reduce morbidity and mortality in these patients; 3) Augmentation therapy is the only specific approved therapy that has shown clinical efficacy in delaying the progression of emphysema. Regrettably, some countries reject registration and reimbursement for this treatment because of the lack of larger randomised, placebo-controlled trials. 4) Alternative strategies are currently being investigated, including the use of gene therapy or induced pluripotent stem cells, and non-augmentation strategies to prevent AAT polymerisation inside hepatocytes.
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Affiliation(s)
- María Torres-Durán
- Pulmonary Department, Hospital Álvaro Cunqueiro EOXI, Vigo, Spain.,NeumoVigo I+i Research Group, IIS Galicia Sur, Vigo, Spain
| | - José Luis Lopez-Campos
- Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Sevilla, Spain.,CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain
| | - Miriam Barrecheguren
- CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.,Pneumology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - Marc Miravitlles
- CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.,Pneumology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - Beatriz Martinez-Delgado
- Molecular Genetics Unit, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Silvia Castillo
- Fundación Investigación Hospital Clínico Valencia, Instituto de Investigación Sanitaria INCLIVA, c/Menéndez y Pelayo, 4, 46010, Valencia, Spain.,School of Medicine, Department of Physiology, Research group on Rare Respiratory Diseases (ERR), University of Valencia, Valencia, Spain
| | - Amparo Escribano
- Fundación Investigación Hospital Clínico Valencia, Instituto de Investigación Sanitaria INCLIVA, c/Menéndez y Pelayo, 4, 46010, Valencia, Spain.,School of Medicine, Department of Paediatrics, Obstetrics and Gynaecology, University of Valencia, Valencia, Spain.,School of Medicine, Department of Physiology, Research group on Rare Respiratory Diseases (ERR), University of Valencia, Valencia, Spain
| | - Adolfo Baloira
- Pneumology Department, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
| | - María Mercedes Navarro-Garcia
- Fundación Investigación Hospital Clínico Valencia, Instituto de Investigación Sanitaria INCLIVA, c/Menéndez y Pelayo, 4, 46010, Valencia, Spain.,School of Medicine, Department of Physiology, Research group on Rare Respiratory Diseases (ERR), University of Valencia, Valencia, Spain
| | - Daniel Pellicer
- Fundación Investigación Hospital Clínico Valencia, Instituto de Investigación Sanitaria INCLIVA, c/Menéndez y Pelayo, 4, 46010, Valencia, Spain.,School of Medicine, Department of Physiology, Research group on Rare Respiratory Diseases (ERR), University of Valencia, Valencia, Spain
| | - Lucía Bañuls
- Fundación Investigación Hospital Clínico Valencia, Instituto de Investigación Sanitaria INCLIVA, c/Menéndez y Pelayo, 4, 46010, Valencia, Spain.,School of Medicine, Department of Physiology, Research group on Rare Respiratory Diseases (ERR), University of Valencia, Valencia, Spain
| | - María Magallón
- Fundación Investigación Hospital Clínico Valencia, Instituto de Investigación Sanitaria INCLIVA, c/Menéndez y Pelayo, 4, 46010, Valencia, Spain.,School of Medicine, Department of Physiology, Research group on Rare Respiratory Diseases (ERR), University of Valencia, Valencia, Spain
| | - Francisco Casas
- Pneumology Department, Hospital Universitario San Cecilio, Granada, Spain
| | - Francisco Dasí
- Fundación Investigación Hospital Clínico Valencia, Instituto de Investigación Sanitaria INCLIVA, c/Menéndez y Pelayo, 4, 46010, Valencia, Spain. .,School of Medicine, Department of Physiology, Research group on Rare Respiratory Diseases (ERR), University of Valencia, Valencia, Spain.
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An Y, Gao S, Zhao WC, Qiu BA, Xia NX, Zhang PJ, Fan ZP. Novel serum microRNAs panel on the diagnostic and prognostic implications of hepatocellular carcinoma. World J Gastroenterol 2018; 24:2596-2604. [PMID: 29962816 PMCID: PMC6021775 DOI: 10.3748/wjg.v24.i24.2596] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Revised: 04/26/2018] [Accepted: 05/05/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To determine a panel of serum microRNAs (miRNAs) that could be used as novel biomarkers for diagnosis of hepatocellular carcinoma (HCC).
METHODS We initially screened 9 out of 754 serum miRNAs by TaqMan Low Density Array in two pooled samples respectively from 35 HCC and 35 normal controls, and then validated individually by RT-qPCR in another 114 patients and 114 controls arranged in two phases. The changes of the selected miRNAs after operation and their prognostic value were examined.
RESULTS miR-375, miR-10a, miR-122 and miR-423 were found to be significantly higher in HCC than in controls (P < 0.0001), and the area under the receiver-operating-characteristic curve for the 4-miRNA panel was 0.995 (95%CI: 0.985-1). All the four miRNAs were significantly reduced after surgical removal of the tumors (P < 0.0001), while still higher than normal controls (at least P < 0.05)
CONCLUSION The four serum miRNAs (miR-375, miR-10a, miR-122 and miR-423) could potentially serve as novel biomarkers for the diagnostic and prognostic of HCC.
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Affiliation(s)
- Yang An
- Department of Hepato-Biliary-Pancreatic Surgey, Navy General Hospital of Chinese People’s Liberation Army, Beijing 100048, China
| | - Song Gao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Interventional Therapy Department, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Wen-Chao Zhao
- Department of Hepato-Biliary-Pancreatic Surgey, Navy General Hospital of Chinese People’s Liberation Army, Beijing 100048, China
| | - Bao-An Qiu
- Department of Hepato-Biliary-Pancreatic Surgey, Navy General Hospital of Chinese People’s Liberation Army, Beijing 100048, China
| | - Nian-Xin Xia
- Department of Hepato-Biliary-Pancreatic Surgey, Navy General Hospital of Chinese People’s Liberation Army, Beijing 100048, China
| | - Peng-Jun Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Interventional Therapy Department, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Zhen-Ping Fan
- The Liver Disease Center for Cadre Medical Care, Beijing 302 Military Hospital, Beijing 100039, China
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35
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Lu J, Tang L, Xu Y, Ge K, Huang J, Gu M, Zhong J, Huang Q. Mir-1287 suppresses the proliferation, invasion, and migration in hepatocellular carcinoma by targeting PIK3R3. J Cell Biochem 2018; 119:9229-9238. [PMID: 29953647 DOI: 10.1002/jcb.27190] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Accepted: 05/24/2018] [Indexed: 12/22/2022]
Abstract
Mature microRNAs (miRNAs) are a class of small noncoding RNA molecules involved in regulation of post-translational gene expression. Although aberrant levels of miRNAs have been found in various tumor tissues, their importance in tumor development and the molecular basis of their regulatory role remain unclear. Our bioinformatic analysis on The Cancer Genome Atlas database and microarray-based comparison of miRNA in different cell lines revealed that the level of mir-1287 is suppressed in hepatocellular carcinoma (HCC) cells. When upregulated, mir-1287 can reduce the tumorigenesis phenotypes of HCC cells in several in vitro models. We further found that mir-1287 directly targets messenger RNA encoding PIK3R3, which is a tumor-promoting factor acting in several pathways linked to tumorigenesis. Our study suggests that aberrant suppression of mir-1287 is potentially responsible for the development of HCC, and miRNA-based strategies may be developed for efficient detection and treatment of HCC.
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Affiliation(s)
- Junhao Lu
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Licheng Tang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Yuqiang Xu
- Shanghai High-Tech United Bio-Technological R&D Co, Ltd, Shanghai, China
| | - Kuikui Ge
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Jinjiang Huang
- Shanghai High-Tech United Bio-Technological R&D Co, Ltd, Shanghai, China
| | - Meigang Gu
- Laboratory of Virology and Infectious Disease Center for the Study of Hepatitis C, Rockefeller University, New York, New York
| | - Jiang Zhong
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Qingshan Huang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.,Shanghai High-Tech United Bio-Technological R&D Co, Ltd, Shanghai, China
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Wang F, Dai M, Chen H, Li Y, Zhang J, Zou Z, Yang H. Prognostic value of hsa-mir-299 and hsa-mir-7706 in hepatocellular carcinoma. Oncol Lett 2018; 16:815-820. [PMID: 29963149 PMCID: PMC6019942 DOI: 10.3892/ol.2018.8710] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 04/17/2018] [Indexed: 12/12/2022] Open
Abstract
This study aimed to investigate the expression of microRNA (miRNA) 299 and miRNA-7706 in patients with hepatocellular carcinoma (HCC), and to explore their effects on proliferation of SK-HEP-1 HCC cells. Expression of miRNA-299 and miRNA-7706 in tumor tissue (HCC group) and adjacent healthy tissue (>30 mm away from the tumor tissue) of 179 patients with HCC was determined by real-time polymerase chain reaction (qRT-PCR). miR-299 mimics and miR-7706 mimics were transfected into SK-HEP-1 HCC cells by RNA transfection. The proliferation and invasion of SK-HEP-1 cells were detected by CCK-8 kit and Transwell kit, respectively. Compared with adjacent tissues, expression levels of miRNA-299 and miRNA-7706 in HCC group were significantly downregulated. Analyses on the correlation between the expression of miRNA-299 and miRNA-7706 and clinical factors showed that expression levels of miRNA-299 and miRNA-7706 were significantly correlated with pathological stages and lymph node metastasis. ROC curve analysis showed that the areas under the curve were 0.837 and 0.845 for miRNA-299 and miRNA-7706 in the prediction of HCC, respectively. Survival analysis showed that the 5-year overall survival rate of patients with high expression levels of miRNA-299 and miRNA-7706 was significantly different from that of patients with low expression levels (P=0.016). Compared with cells transfected with scramble mimics, proliferation and invasion abilities of SK-HEP-1 cells transfected with miR-299 mimics and miRNA-7706 were significantly weakened. Results suggested that downregulation of miRNA-299 and miRNA-7706 can inhibit the proliferation of HCC cells and can be used as a new target for the treatment of HCC.
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Affiliation(s)
- Fenglin Wang
- Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510000, P.R. China
| | - Min Dai
- Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510000, P.R. China
| | - Hongjie Chen
- Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510000, P.R. China
| | - Yue Li
- Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510000, P.R. China
| | - Jiongshan Zhang
- Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510000, P.R. China
| | - Zengcheng Zou
- Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510000, P.R. China
| | - Hongzhi Yang
- Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, Guangdong 510000, P.R. China
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Identification of an 88-microRNA signature in whole blood for diagnosis of hepatocellular carcinoma and other chronic liver diseases. Aging (Albany NY) 2018; 9:1565-1584. [PMID: 28657540 PMCID: PMC5509456 DOI: 10.18632/aging.101253] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Accepted: 06/15/2017] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is a common cancer with very poor survival due to lack of reliable biomarker for early diagnosis. In this study, we investigated microRNA (miRNA) profile of whole blood with a custom microarray containing probes for 1849 miRNA species in a total 213 successive subjects who were divided into a discovery set and a validation set. An 88-miRNA signature was established to diagnose health controls (HC), chronic hepatitis B (CHB), liver cirrhosis (LC) and HCC with 100% accuracy in the discovery set using Fisher discriminant analysis. This diagnostic signature was confirmed in the validation set with accuracy rates of 100%, 95.2%, 93.7% and 98.4% for HC, CHB, LC and HCC patients, respectively. Compared with AFP, the only available non-invasive and routinely used biomarker for diagnosis of HCC, the 88-miRNA signature has much higher accuracy (99.5% vs 76.5%), sensitivity (100% vs 63.8%), and specificity (99.2% vs 84.2%). More importantly, the signature detects small HCCs (<3cm) with 100% (17/17) accuracy while AFP has only 64.7% (11/17). In conclusion, we have identified a powerful and sensitive blood 88-miRNA signature for diagnosing early HCC and other chronic liver diseases (CHB and LC) with a high accuracy.
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Du X, Fan W, Chen Y. microRNA-520f inhibits hepatocellular carcinoma cell proliferation and invasion by targeting TM4SF1. Gene 2018; 657:30-38. [PMID: 29505836 DOI: 10.1016/j.gene.2018.03.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Revised: 02/10/2018] [Accepted: 03/02/2018] [Indexed: 12/21/2022]
Abstract
microRNAs (miRNAs) are reported to play crucial roles in tumorigenesis. Dysregulation of miR-520f has been implicated to be involved in several cancer progressions. However, the biological functions of miR520f in hepatocellular carcinoma (HCC) remain unclear. Thus, the molecular mechanism underlying miR-520f on HCC development was investigated in this study. Here, we found that miR-520f was remarkably down-regulated in human HCC samples and cell lines compared to paired normal tissues and cell lines as detected by qRT-PCR. Furthermore, the deregulated miR-520f was strongly associated with larger tumor size, advanced TNM stage, and metastasis in HCC patients. Functional investigations revealed that overexpression of miR-520f significantly suppressed cell proliferation, invasion and migration, caused cell cycle arrested at G0/G1 phase, and promoted cell apoptosis in HCC cells according to MTT, colony formation, transwell, and flow cytometry assays, respectively, whereas, downregulation of miR-520f exhibited inverse effects. Transmembrane-4 L-Six family member-1 (TM4SF1) was identified as a direct target of miR-520f, and an inverse relationship was found between miR-520f and TM4SF1 mRNA levels in HCC specimens. Rescue experiments suggested that restoration of TM4SF1 partially abolished miR-520f-meidated cell proliferation and invasion inhibition in HCC cells through regulating P13K/AKT and p38 MAPK signaling pathways. In conclusion, these data indicated that miR-520f acted as tumor suppressor in HCC proliferation and invasion by targeting TM4SF1, which might provide potential therapeutic evidence for HCC patients.
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Affiliation(s)
- Xiaoqin Du
- Department of Infectious Diseases, Weinan Center Hospital of Shaanxi Province, Weinan 714000, Shaanxi, China
| | - Wanhu Fan
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
| | - Yunru Chen
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
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A novel microRNAs expression signature for hepatocellular carcinoma diagnosis and prognosis. Oncotarget 2018; 8:8775-8784. [PMID: 28060739 PMCID: PMC5352440 DOI: 10.18632/oncotarget.14452] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Accepted: 12/06/2016] [Indexed: 12/17/2022] Open
Abstract
This study aims to identify prognostic microRNAs (miRNAs) biomarkers for diagnosis and survival of hepatocellular carcinoma (HCC) based on large patients cohort analysis. HCC patient cohort data were downloaded from The Cancer Genome Atlas, including paired HCC and adjacent non-cancer tissues. Receiver operating characteristic curve method was used to classify cancer and non-cancer tissues according to microRNAs expression levels. The aberrant microRNAs expression level were ranked and risked for building a prognostic miRNAs signature model. Kaplan–Meier survival was used to analyze the differences among various risk factors in accordance with miRNAs ranking scores. The study showed 33-miRNA signature, 11 were down-regulated and 22 were up-regulated through comparison between cancer samples and non-cancer samples. The maximum correct classification rate is up to 98.7%. Five microRNAs, hsa-mir-3677, hsa-mir-421, hsa-mir-326, hsa-mir-424 and hsa-mir-511-2, significantly correlated with patient survival. The survival rate and time negatively associated with lowering miRNAs index. In the low risk group, over 70% patients showed 5 years survival, while none patients survived longer than 5 years in the high risk group. MiR-424, miR-326 and miR-511 could be applied for HCC diagnostic biomarkers. These five miRNAs were significantly associated with lysosome pathway and D-Glutamine and D-glutamate metabolism pathway via Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology annotation. Conclusively, the five miRNAs expression signature could be used as HCC prognostic and diagnostic biomarkers.
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40
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Wang F, Wang J, Ju L, Chen L, Cai W, Yang J. Diagnostic and prognostic potential of serum miR-132/212 cluster in patients with hepatocellular carcinoma. Ann Clin Biochem 2018; 55:576-582. [PMID: 29357677 DOI: 10.1177/0004563218755815] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Background It has been reported that both of the miR-132/212 (micro-RNA) cluster members, miR-132 and miR-212, are downregulated in hepatocellular carcinoma. Nevertheless, the expression pattern and clinical utility of serum miR-132/212 in hepatocellular carcinoma are still unknown. Methods In this study, serum concentrations of miR-132 and miR-212 were measured in 80 hepatocellular carcinoma patients, 51 controls with chronic liver diseases and 42 healthy volunteers by using quantitative real-time polymerase chain reaction. Results In hepatocellular carcinoma patients, serum concentrations of miR-132 and miR-212 were significantly reduced and strongly correlated (r = 0.603, p < 0.001). Receiver operator characteristic analyses showed that serum miR-132 and miR-212 might have a potential role in the diagnosis of hepatocellular carcinoma. Moreover, the combination of serum miR-132, miR-212 and alpha-fetoprotein improved the diagnostic efficiency for hepatocellular carcinoma, especially in sensitivity and negative predictive value. Serum miR-132 was associated with tumour differentiation degree ( p = 0.021) and tumour-node-metastasis stage ( p = 0.002); serum miR-212 correlated with tumour size ( p = 0.023) and tumour-node-metastasis stage ( p = 0.007). Kaplan-Meier analyses indicated poorer overall survival in hepatocellular carcinoma patients with lower serum concentrations of miR-132 ( p < 0.001) and miR-212 ( p = 0.005). Conclusions Our results suggest that both components of the miR-132/212 cluster have potential roles as non-invasive serum biomarkers for diagnosis and prognosis of hepatocellular carcinoma.
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Affiliation(s)
- Feng Wang
- 1 Department of Clinical Laboratory, Affiliated Hospital of Nantong University, Nantong, China.,2 Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.,*These authors contributed equally to this work
| | - Jun Wang
- 3 Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, Nanjing University, Nanjing, China.,*These authors contributed equally to this work
| | - Linlin Ju
- 4 Department of Gastroenterology and Clinical Laboratory, Nantong Third Hospital Affiliated to Nantong University, Nantong, China
| | - Lin Chen
- 2 Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.,4 Department of Gastroenterology and Clinical Laboratory, Nantong Third Hospital Affiliated to Nantong University, Nantong, China
| | - Weihua Cai
- 4 Department of Gastroenterology and Clinical Laboratory, Nantong Third Hospital Affiliated to Nantong University, Nantong, China
| | - Jialin Yang
- 2 Prince of Wales Clinical School, University of New South Wales, Sydney, Australia
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41
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Okajima W, Komatsu S, Ichikawa D, Miyamae M, Kawaguchi T, Hirajima S, Ohashi T, Imamura T, Kiuchi J, Arita T, Konishi H, Shiozaki A, Moriumura R, Ikoma H, Okamoto K, Taniguchi H, Itoh Y, Otsuji E. Circulating microRNA profiles in plasma: identification of miR-224 as a novel diagnostic biomarker in hepatocellular carcinoma independent of hepatic function. Oncotarget 2018; 7:53820-53836. [PMID: 27462777 PMCID: PMC5288224 DOI: 10.18632/oncotarget.10781] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 07/09/2016] [Indexed: 12/21/2022] Open
Abstract
Aims This study was designed to identify novel microRNAs (miRNAs) in plasma for detecting and monitoring hepatocellular carcinoma (HCC), independent of hepatic function and background liver diseases with different etiologies. Results (1) Four oncogenic miRNAs (miR-151, 155, 191 and 224) with high expression in HCC tissues were selected as candidates. (2) Quantitative RT-PCR using plasma samples from 107 HCC patients and 75 healthy volunteers revealed a significantly higher level of plasma miR-224 in HCC patients than in healthy volunteers according to a small-scale analysis (P < 0.0001), two independent large-scale cohort analysis (P < 0.0001, AUC 0.908). (3) miR-224 expression was significantly higher in HCC tissues and HCC cell lines than in normal hepatic tissues and fibroblasts, respectively. (P = 0.0011, 0.0150) (4) Plasma miR-224 reflected tumor dynamics; preoperative plasma levels of miR-224 were significantly reduced in postoperative samples (P = 0.0058), and plasma miR-224 levels were significantly correlated with paired miR-224 levels in HCC tissues (P = 0.0005). (5) Furthermore, plasma miR-224 levels significantly discriminated HCC patients from patients with chronic liver disease (P = 0.0008). A high plasma miR-224 level was significantly correlated with larger tumor size (P = 0.0005) and recurrences (P = 0.0027). The plasma miR-224 level could accurately detect small tumors less than 18 mm preoperatively. Methods We performed a systematic review of the NCBI database and selected candidate miRNAs reported as highly expressed in HCC tissue. Conclusions Plasma miR-224 may be a sensitive biomarker for screening HCC and monitoring tumor dynamics.
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Affiliation(s)
- Wataru Okajima
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Shuhei Komatsu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Daisuke Ichikawa
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Mahito Miyamae
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Tsutomu Kawaguchi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Shoji Hirajima
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Takuma Ohashi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Taisuke Imamura
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Jun Kiuchi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Tomohiro Arita
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hirotaka Konishi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Atsushi Shiozaki
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Ryo Moriumura
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hisashi Ikoma
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Kazuma Okamoto
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hiroki Taniguchi
- Department of Surgery, Kyoto Second Red Cross Hospital, Haruobicho, Kamigyo-ku, 602-8026, Kyoto, Japan
| | - Yoshito Itoh
- Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Eigo Otsuji
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
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Chandel R, Saxena R, Das A, Kaur J. Association of rno‐miR‐183‐96‐182 cluster with diethyinitrosamine induced liver fibrosis in Wistar rats. J Cell Biochem 2018; 119:4072-4084. [PMID: 29236317 DOI: 10.1002/jcb.26583] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2017] [Accepted: 12/04/2017] [Indexed: 12/12/2022]
Affiliation(s)
- Rajeev Chandel
- Department of BiochemistryPostgraduate Institute of Medical Education and Research (PGIMER)ChandigarhIndia
| | - Roli Saxena
- Department of BiochemistryPostgraduate Institute of Medical Education and Research (PGIMER)ChandigarhIndia
| | - Ashim Das
- Department of HistopathologyPostgraduate Institute of Medical Education and Research (PGIMER)ChandigarhIndia
| | - Jyotdeep Kaur
- Department of BiochemistryPostgraduate Institute of Medical Education and Research (PGIMER)ChandigarhIndia
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Chiodi I, Scovassi AI, Mondello C. Circulating Molecular and Cellular Biomarkers in Cancer. TRANSLATIONAL TOXICOLOGY AND THERAPEUTICS: WINDOWS OF DEVELOPMENTAL SUSCEPTIBILITY IN REPRODUCTION AND CANCER 2017:607-656. [DOI: 10.1002/9781119023647.ch16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Wang H, Luo J, Liu C, Niu H, Wang J, Liu Q, Zhao Z, Xu H, Ding Y, Sun J, Zhang Q. Investigating MicroRNA and transcription factor co-regulatory networks in colorectal cancer. BMC Bioinformatics 2017; 18:388. [PMID: 28865443 PMCID: PMC5581471 DOI: 10.1186/s12859-017-1796-4] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2016] [Accepted: 08/21/2017] [Indexed: 02/06/2023] Open
Abstract
Background Colorectal cancer (CRC) is one of the most common malignancies worldwide with poor prognosis. Studies have showed that abnormal microRNA (miRNA) expression can affect CRC pathogenesis and development through targeting critical genes in cellular system. However, it is unclear about which miRNAs play central roles in CRC’s pathogenesis and how they interact with transcription factors (TFs) to regulate the cancer-related genes. Results To address this issue, we systematically explored the major regulation motifs, namely feed-forward loops (FFLs), that consist of miRNAs, TFs and CRC-related genes through the construction of a miRNA-TF regulatory network in CRC. First, we compiled CRC-related miRNAs, CRC-related genes, and human TFs from multiple data sources. Second, we identified 13,123 3-node FFLs including 25 miRNA-FFLs, 13,005 TF-FFLs and 93 composite-FFLs, and merged the 3-node FFLs to construct a CRC-related regulatory network. The network consists of three types of regulatory subnetworks (SNWs): miRNA-SNW, TF-SNW, and composite-SNW. To enhance the accuracy of the network, the results were filtered by using The Cancer Genome Atlas (TCGA) expression data in CRC, whereby we generated a core regulatory network consisting of 58 significant FFLs. We then applied a hub identification strategy to the significant FFLs and found 5 significant components, including two miRNAs (hsa-miR-25 and hsa-miR-31), two genes (ADAMTSL3 and AXIN1) and one TF (BRCA1). The follow up prognosis analysis indicated all of the 5 significant components having good prediction of overall survival of CRC patients. Conclusions In summary, we generated a CRC-specific miRNA-TF regulatory network, which is helpful to understand the complex CRC regulatory mechanisms and guide clinical treatment. The discovered 5 regulators might have critical roles in CRC pathogenesis and warrant future investigation. Electronic supplementary material The online version of this article (10.1186/s12859-017-1796-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Hao Wang
- Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.,Department of Pathology, College of Basic Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Jiamao Luo
- Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.,Department of Pathology, College of Basic Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Chun Liu
- Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.,Department of Pathology, College of Basic Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Huilin Niu
- Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.,Department of Pathology, College of Basic Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Jing Wang
- Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA
| | - Qi Liu
- Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA
| | - Zhongming Zhao
- School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.,Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Hua Xu
- School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA
| | - Yanqing Ding
- Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.,Department of Pathology, College of Basic Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Jingchun Sun
- School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
| | - Qingling Zhang
- Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. .,Department of Pathology, College of Basic Medicine, Southern Medical University, Guangzhou, 510515, China.
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Abstract
The accuracy and efficiency of tumor treatment depends mainly on early and precise diagnosis. Although histopathology is always the gold standard for cancer diagnosis, noninvasive biomarkers represent an opportunity for early detection and molecular staging of cancer. Besides the classical tumor markers, noncoding RNAs (ncRNAs) emerge to be a novel category of biomarker for cancer diagnosis since the dysregulation of ncRNAs is closely associated with the development and progression of human cancers such as liver, lung, breast, gastric, and other kinds of cancers. In this chapter, we will summarize the different types of ncRNAs in the diagnosis of major human cancers. In addition, we will introduce the recent advances in the detection and applications of circulating serum or plasma ncRNAs and non-blood fluid ncRNAs because the noninvasive body fluid-based assays are easy to examine for cancer diagnosis and monitoring.
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Abbate V, Marcantoni M, Giuliante F, Vecchio FM, Gatto I, Mele C, Saviano A, Arciuolo D, Gaetani E, Ferrari MC, Giarretta I, Ardito F, Riccardi L, Nicoletti A, Ponziani FR, Gasbarrini A, Pompili M, Pola R. HepPar1-Positive Circulating Microparticles Are Increased in Subjects with Hepatocellular Carcinoma and Predict Early Recurrence after Liver Resection. Int J Mol Sci 2017; 18:E1043. [PMID: 28498353 PMCID: PMC5454955 DOI: 10.3390/ijms18051043] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 04/14/2017] [Accepted: 05/01/2017] [Indexed: 12/19/2022] Open
Abstract
Circulating microparticles (MPs) are novel potential biomarkers in cancer patients. Their role in hepatocellular carcinoma (HCC) is under intensive investigation. In this study, we tested the hypothesis that MPs expressing the antigen HepPar1 are increased in the blood of subjects with HCC and may serve as markers of early recurrence after liver resection (LR). We studied 15 patients affected by HCC undergoing LR, and used flow cytometry to assess the number of circulating HepPar1+ MPs. Ten subjects without HCC (five with liver cirrhosis and five with healthy livers) were used as controls. After LR, HCC patients underwent a follow-up to check for early recurrence, which occurred in seven cases. The number of circulating HepPar1+ MPs was significantly higher in subjects affected by HCC, compared to individuals without cancer (p < 0.01). We also found that, among HCC patients, the number of circulating HepPar1+ MPs, measured before LR, was significantly higher in those who displayed early recurrence compared to those without recurrence (p = 0.02). Of note, other types of circulating MPs, such as those derived from endothelial cells (CD144+) or those produced by the activated endothelium (CD144+/CD62+), were not associated with HCC, nor could they predict HCC recurrence. HepPar1+ MPs deserve further investigation as novel biomarkers of disease and prognosis in HCC patients.
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Affiliation(s)
- Valeria Abbate
- Division of Internal Medicine and Gastroenterology, Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Margherita Marcantoni
- Division of Vascular Medicine, Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Felice Giuliante
- Hepatobiliary Surgery Unit, and Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Fabio M Vecchio
- Department of Pathology, Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Ilaria Gatto
- Division of Vascular Medicine, Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Caterina Mele
- Hepatobiliary Surgery Unit, and Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Antonio Saviano
- Division of Internal Medicine and Gastroenterology, Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Damiano Arciuolo
- Department of Pathology, Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Eleonora Gaetani
- Division of Internal Medicine and Gastroenterology, Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Maria C Ferrari
- Division of Vascular Medicine, Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Igor Giarretta
- Division of Vascular Medicine, Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Francesco Ardito
- Hepatobiliary Surgery Unit, and Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Laura Riccardi
- Division of Internal Medicine and Gastroenterology, Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Alberto Nicoletti
- Division of Internal Medicine and Gastroenterology, Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Francesca R Ponziani
- Division of Internal Medicine and Gastroenterology, Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Antonio Gasbarrini
- Division of Internal Medicine and Gastroenterology, Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Maurizio Pompili
- Division of Internal Medicine and Gastroenterology, Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
| | - Roberto Pola
- Division of Vascular Medicine, Catholic University School of Medicine, A. Gemelli University Hospital, Rome 00168, Italy.
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Wu XM, Xi ZF, Liao P, Huang HD, Huang XY, Wang C, Ma Y, Xia Q, Yao JG, Long XD. Diagnostic and prognostic potential of serum microRNA-4651 for patients with hepatocellular carcinoma related to aflatoxin B1. Oncotarget 2017; 8:81235-81249. [PMID: 29113383 PMCID: PMC5655278 DOI: 10.18632/oncotarget.16027] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Accepted: 02/18/2017] [Indexed: 02/07/2023] Open
Abstract
Background The serum microRNAs have been reported as potential biomarkers for hepatitis virus-related hepatocellular carcinoma (HCC); however, their role in aflatoxin B1 (AFB1)-related HCC to has not yet been evaluated. Materials and Methods We conducted a case-control study, including 366 HCC cases and 662 controls without any evidence of tumors, to identify and assess diagnostic and prognostic potential of serum microRNAs for AFB1-related HCC. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were used to elucidate diagnostic performance, and to compare the microRNAs with α-fetoprotein (AFP) at a cutoff of 20 ng/mL (AFP20) and 400 ng/mL (AFP400). Results We found 8 differentially expressed microRNAs via the microRNA array analysis; however, only microRNA-4651 was further identified to detect AFB1-positive HCC but not AFB1-negative HCC. For AFB1-positive HCC, microRNA-4651 showed higher accuracy and sensitivity than AFP400 (AUC, 0.85 vs. 0.72; Sensitivity, 78.1% vs. 43.0%). Compared to AFP20, microRNA-4651 exhibited higher potential in identifying small-size (0.68 vs. 0.84 for AUC and 36.7% vs. 75.5% for sensitivity, respectively) and early-stage HCC (0.69 vs. 0.84 for AUC and 38.7% vs. 75.7% for sensitivity, respectively). Additionally, miR-4651 was also associated with HCC prognosis (hazard risk value, 2.67 for overall survival and 3.62 for tumor recurrence analysis). Conclusions These data suggest that serum microRNA-4651 may be a useful marker for HCC diagnosis and prognosis, especially AFB1-positive cases.
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Affiliation(s)
- Xue-Min Wu
- Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Zhi-Feng Xi
- Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Pinhu Liao
- Department of Medicine, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Hong-Dong Huang
- Division of Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Xiao-Ying Huang
- Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Chao Wang
- Department of Medicine, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Yun Ma
- Department of Pathology, The Affiliated Tumor Hospital, Guangxi Medical University, Nanning, China
| | - Qiang Xia
- Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jin-Guang Yao
- Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Xi-Dai Long
- Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.,Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Sun B, Xue J, Li J, Luo F, Chen X, Liu Y, Wang Q, Qi C, Zou Z, Zhang A, Liu Q. Circulating miRNAs and their target genes associated with arsenism caused by coal-burning. Toxicol Res (Camb) 2017; 6:162-172. [PMID: 30090486 PMCID: PMC6062399 DOI: 10.1039/c6tx00428h] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Accepted: 01/20/2017] [Indexed: 12/26/2022] Open
Abstract
Endemic arsenism, caused by burning coal containing high levels of arsenic, is found only in the Guizhou and Shanxi Provinces of China. Dysregulated microRNAs (miRNAs), detected in the blood, are emerging as promising biomarkers. At present, little is known about the change and clinical efficacy of circulating miRNAs in patients with endemic arsenism produced by burning of coal. Here, we determined, by using TaqMan Human miRNA Array Chips, the differential expression of plasma miRNAs between patients with arsenism caused by coal-burning and a control group. Four increased miRNAs (miR-21, miR-145, miR-155, and miR-191) were verified in a larger sample by quantitative real-time PCR. Furthermore, bioinformatics and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to associate changes in plasma levels of the miRNAs with their functions and their effects on various pathways. The results of chip array assays show that the levels of miR-21, miR-141, miR-148a, miR-145, miR-155, miR-191, miR-218, and miR-491 were most prominently increased and that the levels of miR-200b, miR-200c, miR-26, and miR-34c were decreased. The qRT-PCR results confirm that the circulating levels of miR-21, miR-145, miR-155, and miR-191 are increased in patients with arsenism caused by coal-burning. KEGG analyses show that these miRNAs inhibit the target genes of pathways related to immune inflammation, oxidative stress, and DNA damage repair. Therefore, the four miRNAs may be biomarkers of endemic arsenism caused by coal-burning. Further studies with larger samples should be performed to confirm these findings and to elucidate the underlying mechanisms.
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Affiliation(s)
- Baofei Sun
- Key Laboratory of Environmental Pollution Monitoring and Disease Control , Ministry of Education , Department of Toxicology , School of Public Health , Guizhou Medical University , Guiyang 550025 , Guizhou , China .
| | - Junchao Xue
- Institute of Toxicology , School of Public Health , Nanjing Medical University , Nanjing 211166 , Jiangsu , China . ; ; Tel: +86-25-8686-8424
| | - Jun Li
- Key Laboratory of Environmental Pollution Monitoring and Disease Control , Ministry of Education , Department of Toxicology , School of Public Health , Guizhou Medical University , Guiyang 550025 , Guizhou , China .
| | - Fei Luo
- Institute of Toxicology , School of Public Health , Nanjing Medical University , Nanjing 211166 , Jiangsu , China . ; ; Tel: +86-25-8686-8424
| | - Xiong Chen
- Key Laboratory of Environmental Pollution Monitoring and Disease Control , Ministry of Education , Department of Toxicology , School of Public Health , Guizhou Medical University , Guiyang 550025 , Guizhou , China .
| | - Yonglian Liu
- Key Laboratory of Environmental Pollution Monitoring and Disease Control , Ministry of Education , Department of Toxicology , School of Public Health , Guizhou Medical University , Guiyang 550025 , Guizhou , China .
| | - Qingling Wang
- Key Laboratory of Environmental Pollution Monitoring and Disease Control , Ministry of Education , Department of Toxicology , School of Public Health , Guizhou Medical University , Guiyang 550025 , Guizhou , China .
| | - Caihua Qi
- Key Laboratory of Environmental Pollution Monitoring and Disease Control , Ministry of Education , Department of Toxicology , School of Public Health , Guizhou Medical University , Guiyang 550025 , Guizhou , China .
| | - Zhonglan Zou
- Key Laboratory of Environmental Pollution Monitoring and Disease Control , Ministry of Education , Department of Toxicology , School of Public Health , Guizhou Medical University , Guiyang 550025 , Guizhou , China .
| | - Aihua Zhang
- Key Laboratory of Environmental Pollution Monitoring and Disease Control , Ministry of Education , Department of Toxicology , School of Public Health , Guizhou Medical University , Guiyang 550025 , Guizhou , China .
| | - Qizhan Liu
- Institute of Toxicology , School of Public Health , Nanjing Medical University , Nanjing 211166 , Jiangsu , China . ; ; Tel: +86-25-8686-8424
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Xiao CZ, Wei W, Guo ZX, Zhang MY, Zhang YF, Wang JH, Shi M, Wang HY, Guo RP. MicroRNA-34c-3p promotes cell proliferation and invasion in hepatocellular carcinoma by regulation of NCKAP1 expression. J Cancer Res Clin Oncol 2017; 143:263-273. [PMID: 27704267 DOI: 10.1007/s00432-016-2280-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Accepted: 09/28/2016] [Indexed: 01/20/2023]
Abstract
PURPOSE Our previous miRNA profiling study indicated that microRNA-34c-3p (miR-34c-3p) was overexpressed and associated with survival in HCC. This study is aimed to confirm its clinical significance and explore the function and underlying mechanism of miR-34c-3p in HCC. METHODS We first evaluated miR-34c-3p expression and its relationship with prognosis in HCC patients. We then established stable HCC cell lines with miR-34c-3p overexpression and knockdown by the lentiviral packaging systems and performed the functional assays in vitro and in vivo, respectively. We next identified the target of miR-34c-3p by using microRNA target databases and dual-luciferase assay. Finally, the correlation between the expression of miR-34c-3p and the target gene was analyzed by immunohistochemistry and qRT-PCR in HCC tissues and hepatoma xenografts. RESULTS Overexpressed miR-34c-3p was confirmed in HCC tissues and significantly associated with poor survival of HCC patients. miR-34c-3p expression was also recognized as an independent risk factor for DFS and OS in multivariate analysis. Ectopic expression of miR-34c-3p significantly promotes the proliferation, colony formation, invasion and cell cycle regression of HCC cell lines. Knockdown of miR-34c-3p remarkably blocked hepatoma growth in the xenograft model. miRNA target databases and luciferase reporter assay showed that NCKAP1 was a direct target of miR-34c-3p in HCC cells and the high expression of NCKAP1 in HCC tissues is significantly correlated with low expression of miR-34c-3p and associated with a favorable prognosis of HCC patients. CONCLUSION The current study demonstrates that miR-34c-3p functions as a tumor promoter by targeting NCKAP1 that is associated with prognosis in HCC. miR-34c-3p and NCKAP1 may be new potential molecular targets for HCC therapy.
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Affiliation(s)
- Cheng-Zuo Xiao
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China
- Department of General Surgery, Shenzhen Shajing Affiliated Hospital of Guangzhou Medical University, Shenzhen, 518100, China
| | - Wei Wei
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Zhi-Xing Guo
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China
| | - Mei-Yin Zhang
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China
| | - Yong-Fa Zhang
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China
| | - Jia-Hong Wang
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China
| | - Ming Shi
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Hui-Yun Wang
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China.
| | - Rong-Ping Guo
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
- Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, China.
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Kim SS, Nam JS, Cho HJ, Won JH, Kim JW, Ji JH, Yang MJ, Park JH, Noh CK, Shin SJ, Lee KM, Cho SW, Cheong JY. Plasma micoRNA-122 as a predictive marker for treatment response following transarterial chemoembolization in patients with hepatocellular carcinoma. J Gastroenterol Hepatol 2017; 32:199-207. [PMID: 27194671 DOI: 10.1111/jgh.13448] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/05/2016] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIM Circulating microRNA (miR)-122 has recently been investigated as a potential biomarker of various hepatic diseases, such as chronic hepatitis and hepatocellular carcinoma (HCC). We investigated the association between plasma miR-122 levels and the treatment outcomes following transarterial chemoembolization (TACE) in HCC patients. METHODS We included 177 HCC patients treated with TACE in the study; TACE refractoriness and liver transplantation-free survival were evaluated during follow up. Pretreatment plasma miR-122 levels were assessed using quantitative real-time polymerase chain reaction. Relative quantification of miR-122 expression (fold change) was determined using the 2(-ΔΔCt) method. MiR-16 was used as an internal control for the normalization of miRNA data. RESULTS During the mean follow up of 22.4 (range, 1-79) months, 112 (69.5%) patients exhibited TACE refractoriness. Multivariate analyses showed that tumor number (hazard ratio [HR], 2.51; 95% confidence interval [CI], 1.43-4.41; P = 0.001) and tumor size (HR, 2.65; 95% CI, 1.62-4.32; P = 0.000) can independently predict overall TACE refractoriness. High miR-122 expression (> 100) was associated with early TACE refractoriness (within 1 year; HR, 2.77; 95% CI, 1.12-6.86; P = 0.028), together with tumor number (HR, 22.73; 95% CI, 2.74-188.66; P = 0.004) and tumor size (HR, 4.90; 95% CI, 1.99-12.06; P = 0.001). Univariate analyses showed that high miR-122 expression tends to be associated with poor liver transplantation-free survival (HR, 1.42; 95% CI, 0.95-2.11; P = 0.085). However, it was statistically insignificant in multivariate analysis. CONCLUSION High expression levels of plasma miR-122 are associated with early TACE refractoriness in HCC patients treated with TACE.
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Affiliation(s)
- Soon Sun Kim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Ji Sun Nam
- Human Genome Research and Bio-Resource Center, Ajou University Medical Center, Suwon, South Korea
| | - Hyo Jung Cho
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Je Hwan Won
- Department of Radiology, Ajou University School of Medicine, Suwon, South Korea
| | - Jin Woo Kim
- Department of Radiology, Ajou University School of Medicine, Suwon, South Korea
| | - Jae-Hoon Ji
- Genomic Instability Research Center, Ajou University School of Medicine, Suwon, South Korea
| | - Min Jae Yang
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Joo Han Park
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Choong-Kyun Noh
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Sung Jae Shin
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Kee Myung Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Sung Won Cho
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Jae Youn Cheong
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
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