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Qian X, Jiang Y, Yang Y, Zhang Y, Xu N, Xu B, Pei K, Yu Z, Wu W. Recent advances of miR-23 in human diseases and growth development. Noncoding RNA Res 2025; 11:220-233. [PMID: 39896346 PMCID: PMC11787465 DOI: 10.1016/j.ncrna.2024.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 12/17/2024] [Accepted: 12/29/2024] [Indexed: 02/04/2025] Open
Abstract
MicroRNA (miRNA) is broadly manifested in eukaryotes and serves as a critical function in biological development and disease occurrence. With the rapid advancement of experimental research tools, researchers have discovered functional correlations among different miRNA isoforms and clusters within the same miRNA family. As a highly conserved member in the miR-23-27-24 cluster, miR-23 exhibits different isoforms and participates in various essential development. Although the miR-23-27-24 cluster has overlapping target sites, their differential expression can demonstrate independent biological functions. Furthermore, the untapped effects of miR-23 on organisms, whether as a functional cluster or a single regulator, has not been systematically elucidated yet. In this review article, we analyze the genomic location of miR-23 and its sequence variances among its isoforms or family members while summarizing its regulatory functions in metabolic diseases, immune responses, cardiovascular diseases, cancer, organ development as well as nervous system function. This review highlights the significant role of miR-23 as a biomarker for disease diagnosis and a key regulatory factor in pathogenesis, which can help us comprehend the diverse functions of miRNAs and provide a theoretical reference for the functional differences among miRNA isoforms.
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Affiliation(s)
- Xu Qian
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, School of Acupuncture-Moxibustion and Tuina, School of Health Preservation and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yongwei Jiang
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, School of Acupuncture-Moxibustion and Tuina, School of Health Preservation and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yadi Yang
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, School of Acupuncture-Moxibustion and Tuina, School of Health Preservation and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yukun Zhang
- School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China
| | - Na Xu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, School of Acupuncture-Moxibustion and Tuina, School of Health Preservation and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Bin Xu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, School of Acupuncture-Moxibustion and Tuina, School of Health Preservation and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Ke Pei
- School of Traditional Chinese Medicine and School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Zhi Yu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, School of Acupuncture-Moxibustion and Tuina, School of Health Preservation and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Wei Wu
- Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, School of Acupuncture-Moxibustion and Tuina, School of Health Preservation and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing, 210023, China
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Karaca Dogan B, Salman Yilmaz S, Izgi GN, Ozen M. Circulating non-coding RNAs as a tool for liquid biopsy in solid tumors. Epigenomics 2025; 17:335-358. [PMID: 40040488 PMCID: PMC11970797 DOI: 10.1080/17501911.2025.2467021] [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: 08/16/2024] [Accepted: 02/10/2025] [Indexed: 03/06/2025] Open
Abstract
Solid tumors are significant causes of global mortality and morbidity. Recent research has primarily concentrated on finding pathology-specific molecules that can be acquired non-invasively and that can change as the disease progresses or in response to treatment. The focus of research has moved to RNA molecules that are either freely circulating in body fluids or bundled in microvesicles and exosomes because of their great stability in challenging environments, ease of accessibility, and changes in level in response to therapy. In this context, there are many non-coding RNAs that can be used for this purpose in liquid biopsies. Out of these, microRNAs have been extensively studied. However, there has been an increase of interest in studying long non-coding RNAs, piwi interacting RNAs, circular RNAs, and other small non-coding RNAs. In this article, an overview of the most researched circulating non-coding RNAs in solid tumors will be reviewed, along with a discussion of the significance of these molecules for early diagnosis, prognosis, and therapeutic targets. The publications analyzed were extracted from the PubMed database between 2008 and June 2024.
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Affiliation(s)
- Beyza Karaca Dogan
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
| | - Seda Salman Yilmaz
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
- Department of Medical Services and Techniques Medical Monitoring Techniques Pr. Vocational School of Health Services, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
| | - Gizem Nur Izgi
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
| | - Mustafa Ozen
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
- Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA
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3
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Zhang B, Zhu B, Yu J, Liu H, Zhou Y, Sun G, Ma Y, Luan Y, Chen M. A combined model of six serum microRNAs as diagnostic markers for hepatocellular carcinoma. Clin Chim Acta 2025; 565:119977. [PMID: 39332657 DOI: 10.1016/j.cca.2024.119977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 09/23/2024] [Accepted: 09/23/2024] [Indexed: 09/29/2024]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is associated with high morbidity and mortality, and its poor prognosis is mainly due to the lack of an effective means of early diagnosis. This study aimed to identify a group of serum microRNAs (miRNAs) as potential biomarkers for the diagnosis of HCC. METHODS We collected 190 HCC cases, 109 benign lesions of the liver, 40 cases of non-HCC tumors, and 130 healthy controls. The 469 participants were divided into training and validation sets. A literature search revealed 12 miRNAs closely associated with HCC. In the training set, significantly differentially expressed miRNAs (DEmiRNAs) were screened using real-time quantitative PCR, and a diagnostic model of HCC was constructed using logistic regression analysis. An independent validation was performed using a validation set. The identified DE miRNAs were subjected to target gene prediction and functional analyses. RESULTS Compared to the controls, the levels of miR-21, miR-221, miR-801, and miR-1246 significantly decreased in HCC (P < 0.05), while the levels of miR-26a and miR-122 significantly increased (P < 0.05). A diagnostic model based on the six DE miRNAs was successfully constructed, with AUC values of 0.953 for the training set and 0.952 for the verification set. Finally, 100 target genes of the DE miRNAs were predicted and were significantly enriched in the B cell receptor, neurotrophin, ferroptosis, and EGFR tyrosine kinase inhibitor resistance signaling pathways. CONCLUSIONS The constructed diagnostic model based on six DE miRNA combinations has important clinical value for the early diagnosis of HCC.
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Affiliation(s)
- Bingqiang Zhang
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, Shandong 266111, PR China
| | - Boyang Zhu
- School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, PR China
| | - Junmei Yu
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, Shandong 266111, PR China
| | - He Liu
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, Shandong 266111, PR China
| | - Yang Zhou
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, Shandong 266111, PR China
| | - Guolong Sun
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, Shandong 266111, PR China
| | - Yongchao Ma
- School of Chemistry and Pharmacy, Qingdao Agricultural University, Qingdao, Shandong 266111, PR China
| | - Yansong Luan
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, Shandong 266111, PR China.
| | - Mengmeng Chen
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, Shandong 266111, PR China.
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Zhang B, Ma X, Zhou Y, Zhu B, Yu J, Liu H, Ma Y, Luan Y, Chen M. Diagnostic Value of Circulating microRNAs for Hepatocellular Carcinoma: Results of a Meta-analysis and Validation. Biochem Genet 2025:10.1007/s10528-024-11001-2. [PMID: 39751721 DOI: 10.1007/s10528-024-11001-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 12/09/2024] [Indexed: 01/04/2025]
Abstract
Mounting evidence suggests that circulating microRNAs (miRNAs) hold diagnostic value in various malignancies. To identify circulating miRNAs for the early diagnosis of hepatocellular carcinoma (HCC), we conducted a meta-analysis to evaluate the diagnostic utility of miRNAs in HCC and further validated the results of the meta-analysis. English articles published prior to December 2023 were retrieved from databases including PubMed, Embase, and Web of Science. A random-effects or fixed-effects model was applied depending on the heterogeneity among studies. The pooled sensitivity, specificity, and the area under the summary receiver operating characteristic curve (AUC) were calculated to assess diagnostic accuracy. Additionally, RT-qPCR and receiver operating characteristic (ROC) analyses were employed to further validate the findings. A total of 36 studies were included, involving 3362 patients with HCC and 2150 patients with chronic hepatitis. The pooled sensitivity, specificity, and diagnostic odds ratio were 0.79 (95% CI 0.75-0.82), 0.79 (95% CI 0.73-0.84), and 14 (95% CI 9-22), respectively; the positive and negative likelihood ratios were 4.0 and 0.27, respectively; the area under the curve (AUC) in the summary receiver operating characteristic (ROC) was 0.85 (95% CI 0.82-0.88). Validation indicated a significant upregulation of miR-1246, miR-21, and miR-221 in HCC patients compared to those with chronic hepatitis (P < 0.01), while miR-122 and miR-26a were significantly downregulated (P < 0.01). Moreover, the validation results also demonstrated that serum levels of miR-21, miR-26a, miR-122, miR-221, and miR-1246 exhibit high sensitivity and specificity in the diagnosis of HCC. Circulating miRNAs may be promising biomarkers for HCC diagnosis.
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Affiliation(s)
- Bingqiang Zhang
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China
| | - Xiaoyan Ma
- Department of Oncology, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, 266111, Shandong, People's Republic of China
| | - Yang Zhou
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China
| | - Boyang Zhu
- School of Clinical and Basic Medical Sciences, Shandong First Medical, University& Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, People's Republic of China
| | - Junmei Yu
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China
| | - He Liu
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China
| | - Yongchao Ma
- College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao, 266111, Shandong, People's Republic of China
| | - Yansong Luan
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China.
| | - Mengmeng Chen
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China.
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Umezu T, Mori T, Toyoda H, Kanekura K, Tamori A, Ochiya T, Kuroda M, Akutsu T, Murakami Y. Analysis of Carcinogenic Involvement of MicroRNA Pattern in Peripheral Non-Cancerous Tissues and Chronic Viral Liver Injury. Int J Mol Sci 2024; 25:7858. [PMID: 39063098 PMCID: PMC11277156 DOI: 10.3390/ijms25147858] [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: 05/31/2024] [Revised: 07/11/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
Risk factors for hepatocarcinogenesis include chronic inflammation due to viral infection, liver fibrosis, and aging. In this study, we separated carcinogenic and non-carcinogenic cases due to hepatitis C virus (HCV) infection, aiming to comprehensively analyze miRNA expression in liver tissues by age, and identify factors that contribute to carcinogenesis. Total RNA was extracted from 360 chronic hepatitis C (CH), 43 HCV infected hepatocellular carcinoma (HCC), and surrounding non-tumor (SNT) tissues. MicroRNA (miRNA) expression patterns were analyzed using microarray. Using machine learning, we extracted characteristic miRNA expression patterns for each disease and age. There were no age-dependent changes in miRNA expression in the disease-specific comparisons; however, miRNA expression differed among the age groups of 50, 60, and 70 years of age between CH and SNT. The expression of miRNA was different between SNT and HCC only in patients in their 70s. Of the 55 miRNAs with significant differences in expression between CH and SNT, 34 miRNAs showed significant differences in expression even in the degree of liver fibrosis. The observation that miRNAs involved in hepatocarcinogenesis differ at different ages suggests that the mechanisms of carcinogenesis differ by age group as well. We also found that many miRNAs whose expression did not affect liver fibrosis were involved in carcinogenesis. These findings are expected to define biomarkers for detection of HCC at early stage, and develop novel therapeutic targets for HCC.
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Affiliation(s)
- Tomohiro Umezu
- Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan; (T.U.); (K.K.); (M.K.)
| | - Tomoya Mori
- Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan; (T.M.); (T.A.)
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki, Gifu 503-8502, Japan;
| | - Kohsuke Kanekura
- Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan; (T.U.); (K.K.); (M.K.)
| | - Akihiro Tamori
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan;
| | - Takahiro Ochiya
- Institution of Medical Science, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan;
| | - Masahiko Kuroda
- Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan; (T.U.); (K.K.); (M.K.)
| | - Tatsuya Akutsu
- Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan; (T.M.); (T.A.)
| | - Yoshiki Murakami
- Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan; (T.U.); (K.K.); (M.K.)
- Department of Dentistry, Asahi University, 3-23 Hashimoto-cho, Gifu 500-8523, Japan
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Elghoroury EA, Abdelghafar EE, Kamel S, Awadallah E, Shalaby A, EL-Saeed GSM, Mahmoud E, Kamel MM, Abobakr A, Yousef RN. Dysregulation of miR-122, miR-574 and miR-375 in Egyptian patients with breast cancer. PLoS One 2024; 19:e0298536. [PMID: 38820252 PMCID: PMC11142443 DOI: 10.1371/journal.pone.0298536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 01/25/2024] [Indexed: 06/02/2024] Open
Abstract
BACKGROUND The early detection of breast cancer (BC) is receiving global attention, creating an urgent need for more sensitive and comprehensive strategies for preventive intervention, therapy assessment, and prognosis prediction. Aberrant expression of miRNAs has been observed in various malignancies and may be potential targets for therapy. Our study aims to examine the expression profiles of miR-375, miR-574-3p, and miR-122 in the sera of Egyptian women with BC, benign breast lesions, and a control group. We hope to determine if these miRNAs can serve as minimally invasive biomarkers for BC. METHODS This is a case-control study in which 77 patients with newly diagnosed BC, 20 patients with benign breast tumors, and 30 normal healthy subjects as controls were recruited from the outpatient clinic of the National Cancer Institute. The assessment of miRNAs was conducted using RT-PCR (Applied Biosystems). RESULTS The expression level of miRNA-122 was significantly upregulated in the BC group, while the expression levels of miRNA-574 and miRNA-375 showed significant downregulation in BC patients. Serum miR-122 and miRNA-375 were able to distinguish breast cancer from the benign and control groups in ROC curve analysis, with AUCs of 0.786 and 0.796, respectively. Our results also showed that serum miR-122 and miR-574 are significant predictor variables in the multivariate analysis, after adjusting for age. CONCLUSIONS Our findings suggest that miR-122 may act as an onco-microRNA, while miR-574 and miR-375 may have a main tumour suppressor role. The studied miRNAs may serve as minimally invasive biomarkers for cases of breast cancer and as promising potential therapeutic targets for breast cancer.
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Affiliation(s)
- Eman A. Elghoroury
- Department of Clinical & Chemical Pathology, Medical Research and Clinical Studies Institute, National Research Center, Giza, Egypt
| | - Esmat E. Abdelghafar
- Department of Clinical & Chemical Pathology, Medical Research and Clinical Studies Institute, National Research Center, Giza, Egypt
| | - Solaf Kamel
- Department of Clinical & Chemical Pathology, Medical Research and Clinical Studies Institute, National Research Center, Giza, Egypt
| | - Eman Awadallah
- Department of Clinical & Chemical Pathology, Medical Research and Clinical Studies Institute, National Research Center, Giza, Egypt
| | - Aliaa Shalaby
- Department of Clinical & Chemical Pathology, Medical Research and Clinical Studies Institute, National Research Center, Giza, Egypt
| | - Gamila S. M. EL-Saeed
- Medical Biochemistry, Medical Research and Clinical Studies Institute, National Research Center, Giza, Egypt
| | - Eman Mahmoud
- Department of Clinical & Chemical Pathology, Medical Research and Clinical Studies Institute, National Research Center, Giza, Egypt
| | - Mahmoud M. Kamel
- Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Asmaa Abobakr
- Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt
- Baheya Centre for Early Detection and Treatment of Breast Cancer, Giza, Egypt
| | - Rasha Nazih Yousef
- Department of Clinical & Chemical Pathology, Medical Research and Clinical Studies Institute, National Research Center, Giza, Egypt
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Wu K, Zhang G, Shen C, Zhu L, Yu C, Sartorius K, Ding W, Jiang Y, Lu Y. Role of T cells in liver metastasis. Cell Death Dis 2024; 15:341. [PMID: 38755133 PMCID: PMC11099083 DOI: 10.1038/s41419-024-06726-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 04/24/2024] [Accepted: 05/07/2024] [Indexed: 05/18/2024]
Abstract
The liver is a major metastatic site (organ) for gastrointestinal cancers (such as colorectal, gastric, and pancreatic cancers) as well as non-gastrointestinal cancers (such as lung, breast, and melanoma cancers). Due to the innate anatomical position of the liver, the apoptosis of T cells in the liver, the unique metabolic regulation of hepatocytes and other potential mechanisms, the liver tends to form an immunosuppressive microenvironment and subsequently form a pre-metastatic niche (PMN), which can promote metastasis and colonization by various tumor cells(TCs). As a result, the critical role of immunoresponse in liver based metastasis has become increasingly appreciated. T cells, a centrally important member of adaptive immune response, play a significant role in liver based metastases and clarifying the different roles of the various T cells subsets is important to guide future clinical treatment. In this review, we first introduce the predisposing factors and related mechanisms of liver metastasis (LM) before introducing the PMN and its transition to LM. Finally, we detail the role of different subsets of T cells in LM and advances in the management of LM in order to identify potential therapeutic targets for patients with LM.
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Affiliation(s)
- Kejia Wu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Guozhu Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
- Department of Emergency Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Changbing Shen
- Department of Hepatobiliary and Pancreatic Surgery, Taizhou Second People's Hospital Affiliated with Yangzhou University, Taizhou, China
| | - Li Zhu
- Department of Hepatobiliary and Pancreatic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
- Department of Emergency Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Chongyuan Yu
- Department of Hepatobiliary and Pancreatic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Kurt Sartorius
- School of Laboratory Medicine and Molecular Sciences, University of Kwazulu-Natal, Durban, South Africa
- Africa Hepatopancreatobiliary Cancer Consortium, Mayo Clinic, Jacksonville, FL, USA
| | - Wei Ding
- Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China.
- Department of General Surgery, The Wujin Clinical College of Xuzhou Medical University, Changzhou, China.
- Changzhou Medical Center, Nanjing Medical University, Changzhou, China.
| | - Yong Jiang
- Department of Hepatobiliary and Pancreatic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China.
| | - Yunjie Lu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
- Africa Hepatopancreatobiliary Cancer Consortium, Mayo Clinic, Jacksonville, FL, USA.
- Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China.
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8
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Yerukala Sathipati S, Aimalla N, Tsai MJ, Carter T, Jeong S, Wen Z, Shukla SK, Sharma R, Ho SY. Prognostic microRNA signature for estimating survival in patients with hepatocellular carcinoma. Carcinogenesis 2023; 44:650-661. [PMID: 37701974 DOI: 10.1093/carcin/bgad062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 08/01/2023] [Accepted: 09/08/2023] [Indexed: 09/14/2023] Open
Abstract
OBJECTIVE Hepatocellular carcinoma (HCC) is one of the leading cancer types with increasing annual incidence and high mortality in the USA. MicroRNAs (miRNAs) have emerged as valuable prognostic indicators in cancer patients. To identify a miRNA signature predictive of survival in patients with HCC, we developed a machine learning-based HCC survival estimation method, HCCse, using the miRNA expression profiles of 122 patients with HCC. METHODS The HCCse method was designed using an optimal feature selection algorithm incorporated with support vector regression. RESULTS HCCse identified a robust miRNA signature consisting of 32 miRNAs and obtained a mean correlation coefficient (R) and mean absolute error (MAE) of 0.87 ± 0.02 and 0.73 years between the actual and estimated survival times of patients with HCC; and the jackknife test achieved an R and MAE of 0.73 and 0.97 years between actual and estimated survival times, respectively. The identified signature has seven prognostic miRNAs (hsa-miR-146a-3p, hsa-miR-200a-3p, hsa-miR-652-3p, hsa-miR-34a-3p, hsa-miR-132-5p, hsa-miR-1301-3p and hsa-miR-374b-3p) and four diagnostic miRNAs (hsa-miR-1301-3p, hsa-miR-17-5p, hsa-miR-34a-3p and hsa-miR-200a-3p). Notably, three of these miRNAs, hsa-miR-200a-3p, hsa-miR-1301-3p and hsa-miR-17-5p, also displayed association with tumor stage, further emphasizing their clinical relevance. Furthermore, we performed pathway enrichment analysis and found that the target genes of the identified miRNA signature were significantly enriched in the hepatitis B pathway, suggesting its potential involvement in HCC pathogenesis. CONCLUSIONS Our study developed HCCse, a machine learning-based method, to predict survival in HCC patients using miRNA expression profiles. We identified a robust miRNA signature of 32 miRNAs with prognostic and diagnostic value, highlighting their clinical relevance in HCC management and potential involvement in HCC pathogenesis.
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Affiliation(s)
| | - Nikhila Aimalla
- Department of Internal Medicine-Pediatrics, Marshfield Clinic Health System, Marshfield, WI 54449, USA
| | - Ming-Ju Tsai
- Hinda and Arthur Marcus Institute for Aging Research at Hebrew Senior Life, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - Tonia Carter
- Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield, WI 54449, USA
| | - Sohyun Jeong
- Hinda and Arthur Marcus Institute for Aging Research at Hebrew Senior Life, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - Zhi Wen
- Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield, WI 54449, USA
| | - Sanjay K Shukla
- Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield, WI 54449, USA
| | - Rohit Sharma
- Department of Surgical Oncology, Marshfield Clinic Health System, Marshfield, WI 54449, USA
| | - Shinn-Ying Ho
- Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
- College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan
- Biomedical Engineering, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
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9
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Al-Gazally ME, Khan R, Imran M, Ramírez-Coronel AA, Alshahrani SH, Altalbawy FMA, Turki Jalil A, Romero-Parra RM, Zabibah RS, Shahid Iqbal M, Karampoor S, Mirzaei R. The role and mechanism of action of microRNA-122 in cancer: Focusing on the liver. Int Immunopharmacol 2023; 123:110713. [PMID: 37523968 DOI: 10.1016/j.intimp.2023.110713] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 07/08/2023] [Accepted: 07/24/2023] [Indexed: 08/02/2023]
Abstract
microRNA-122 (miR-122) is a highly conserved microRNA that is predominantly expressed in the liver and plays a critical role in the regulation of liver metabolism. Recent studies have shown that miR-122 is involved in the pathogenesis of various types of cancer, particularly liver cancer. In this sense, The current findings highlighted the potential role of miR-122 in regulating many vital processes in cancer pathophysiology, including apoptosis, signaling pathway, cell metabolism, immune system response, migration, and invasion. These results imply that miR-122, which has been extensively studied for its biological functions and potential therapeutic applications, acts as a tumor suppressor or oncogene in cancer development. We first provide an overview and summary of the physiological function and mode of action of miR-122 in liver cancer. We will examine the various signaling pathways and molecular mechanisms through which miR-122 exerts its effects on cancer cells, including the regulation of oncogenic and tumor suppressor genes, the modulation of cell proliferation and apoptosis, and the regulation of metastasis. Most importantly, we will also discuss the potential diagnostic and therapeutic applications of miR-122 in cancer, including the development of miRNA-based biomarkers for cancer diagnosis and prognosis, and the potential use of miR-122 as a therapeutic target for cancer treatment.
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Affiliation(s)
| | - Ramsha Khan
- MBBS, Nawaz Sharif Medical College, Gujrat, Pakistan
| | - Muhammad Imran
- MBBS, Multan Medical and Dental College, Multan, Pakistan
| | | | | | - Farag M A Altalbawy
- National Institute of Laser Enhanced Sciences (NILES), University of Cairo, Giza 12613, Egypt; Department of Chemistry, University College of Duba, University of Tabuk, Tabuk, Saudi Arabia
| | - Abduladheem Turki Jalil
- Medical Laboratories Techniques Department, Al-Mustaqbal University College, Babylon, Hilla 51001, Iraq
| | | | - Rahman S Zabibah
- Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq
| | - Muhammad Shahid Iqbal
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam bin Abdulaziz University, 11942 Alkharj, Saudi Arabia
| | - Sajad Karampoor
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Rasoul Mirzaei
- Venom and Biotherapeutics Molecules Lab, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
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10
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Kan Changez MI, Mubeen M, Zehra M, Samnani I, Abdul Rasool A, Mohan A, Wara UU, Tejwaney U, Kumar V. Role of microRNA in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH): a comprehensive review. J Int Med Res 2023; 51:3000605231197058. [PMID: 37676968 PMCID: PMC10492500 DOI: 10.1177/03000605231197058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 08/08/2023] [Indexed: 09/09/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver condition that affects people who do not overconsume alcohol. Uncertainties exist over how microRNAs (miRNAs) in the blood and liver relate to NAFLD. The aim of this narrative review was to investigate the role of miRNAs in the onset and progression of non-alcoholic steatohepatitis (NASH) from NAFLD, and explore their potential as diagnostic tools and treatment targets for NAFLD patients. Liver miRNA-34a levels were found to accurately represent the degree of liver damage, with lower levels suggesting more damage. In patients with NAFLD and severe liver fibrosis, higher levels of miRNA-193a-5p and miRNA-378d were found. Moreover, miRNA-34a, miRNA-122, and miRNA-192 levels might aid in differentiating NASH from NAFLD. Similar to this, miRNA-21 and miRNA-27 levels in rats were able to distinguish between steatosis and steatohepatitis. High-fat diets enhanced the expression of 15 distinct miRNAs in rats, and there were substantial differences in the miRNA expression patterns between obese and lean people. The results from the present review imply that miRNA microarrays and sequencing may be helpful diagnostic tools, and miRNAs may be a possible treatment target for patients with NAFLD.
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Affiliation(s)
- Mah I Kan Changez
- Department of Medicine, Quetta Institute of Medical Sciences, Quetta, Pakistan
| | - Maryam Mubeen
- Department of Medicine, Punjab Medical College, Faisalabad, Pakistan
| | - Monezahe Zehra
- Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan
| | - Inara Samnani
- Department of Medicine, Karachi Medical & Dental College, Karachi, Pakistan
| | | | - Anmol Mohan
- Department of Medicine, Karachi Medical & Dental College, Karachi, Pakistan
| | - Um Ul Wara
- Department of Medicine, Karachi Medical & Dental College, Karachi, Pakistan
| | - Usha Tejwaney
- Department of Pharmacy, Valley Health System, New Jersey, USA
| | - Vikash Kumar
- Department of Internal Medicine, The Brooklyn Hospital Center, New York City, NY, USA
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11
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Afra F, Mahboobipour AA, Salehi Farid A, Ala M. Recent progress in the immunotherapy of hepatocellular carcinoma: Non-coding RNA-based immunotherapy may improve the outcome. Biomed Pharmacother 2023; 165:115104. [PMID: 37393866 DOI: 10.1016/j.biopha.2023.115104] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 06/27/2023] [Accepted: 06/28/2023] [Indexed: 07/04/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the second most lethal cancer and a leading cause of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) significantly improved the prognosis of HCC; however, the therapeutic response remains unsatisfactory in a substantial proportion of patients or needs to be further improved in responders. Herein, other methods of immunotherapy, including vaccine-based immunotherapy, adoptive cell therapy, cytokine delivery, kynurenine pathway inhibition, and gene delivery, have been adopted in clinical trials. Although the results were not encouraging enough to expedite their marketing. A major proportion of human genome is transcribed into non-coding RNAs (ncRNAs). Preclinical studies have extensively investigated the roles of ncRNAs in different aspects of HCC biology. HCC cells reprogram the expression pattern of numerous ncRNAs to decrease the immunogenicity of HCC, exhaust the cytotoxic and anti-cancer function of CD8 + T cells, natural killer (NK) cells, dendritic cells (DCs), and M1 macrophages, and promote the immunosuppressive function of T Reg cells, M2 macrophages, and myeloid-derived suppressor cells (MDSCs). Mechanistically, cancer cells recruit ncRNAs to interact with immune cells, thereby regulating the expression of immune checkpoints, functional receptors of immune cells, cytotoxic enzymes, and inflammatory and anti-inflammatory cytokines. Interestingly, prediction models based on the tissue expression or even serum levels of ncRNAs could predict response to immunotherapy in HCC. Moreover, ncRNAs markedly potentiated the efficacy of ICIs in murine models of HCC. This review article first discusses recent advances in the immunotherapy of HCC, then dissects the involvement and potential application of ncRNAs in the immunotherapy of HCC.
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Affiliation(s)
- Fatemeh Afra
- Clinical Pharmacy Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Ali Mahboobipour
- Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Salehi Farid
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Moein Ala
- Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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12
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Hackl LM, Fenn A, Louadi Z, Baumbach J, Kacprowski T, List M, Tsoy O. Alternative splicing impacts microRNA regulation within coding regions. NAR Genom Bioinform 2023; 5:lqad081. [PMID: 37705830 PMCID: PMC10495541 DOI: 10.1093/nargab/lqad081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 08/04/2023] [Accepted: 09/06/2023] [Indexed: 09/15/2023] Open
Abstract
MicroRNAs (miRNAs) are small non-coding RNA molecules that bind to target sites in different gene regions and regulate post-transcriptional gene expression. Approximately 95% of human multi-exon genes can be spliced alternatively, which enables the production of functionally diverse transcripts and proteins from a single gene. Through alternative splicing, transcripts might lose the exon with the miRNA target site and become unresponsive to miRNA regulation. To check this hypothesis, we studied the role of miRNA target sites in both coding and non-coding regions using six cancer data sets from The Cancer Genome Atlas (TCGA) and Parkinson's disease data from PPMI. First, we predicted miRNA target sites on mRNAs from their sequence using TarPmiR. To check whether alternative splicing interferes with this regulation, we trained linear regression models to predict miRNA expression from transcript expression. Using nested models, we compared the predictive power of transcripts with miRNA target sites in the coding regions to that of transcripts without target sites. Models containing transcripts with target sites perform significantly better. We conclude that alternative splicing does interfere with miRNA regulation by skipping exons with miRNA target sites within the coding region.
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Affiliation(s)
- Lena Maria Hackl
- Institute for Computational Systems Biology, University of Hamburg, Notkestrasse 9, 22607 Hamburg, Germany
| | - Amit Fenn
- Institute for Computational Systems Biology, University of Hamburg, Notkestrasse 9, 22607 Hamburg, Germany
- Chair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, Maximus-von-Imhof-Forum 3, 85354 Freising, Germany
| | - Zakaria Louadi
- Institute for Computational Systems Biology, University of Hamburg, Notkestrasse 9, 22607 Hamburg, Germany
- Chair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, Maximus-von-Imhof-Forum 3, 85354 Freising, Germany
| | - Jan Baumbach
- Institute for Computational Systems Biology, University of Hamburg, Notkestrasse 9, 22607 Hamburg, Germany
- Computational BioMedicine Lab, University of Southern Denmark, Campusvej 50, 5230 Odense, Denmark
| | - Tim Kacprowski
- Division Data Science in Biomedicine, Peter L. Reichertz Institute for Medical Informatics of TU Braunschweig and Hannover Medical School, Rebenring 56, 38106 Braunschweig, Germany
- Braunschweig Integrated Centre of Systems Biology (BRICS), TU Braunschweig, Rebenring 56, 38106 Braunschweig, Germany
| | - Markus List
- Chair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, Maximus-von-Imhof-Forum 3, 85354 Freising, Germany
| | - Olga Tsoy
- Institute for Computational Systems Biology, University of Hamburg, Notkestrasse 9, 22607 Hamburg, Germany
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13
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Samarasinghe SM, Hewage AS, Siriwardana RC, Tennekoon KH, Niriella MA, De Silva S. Genetic and metabolic aspects of non-alcoholic fatty liver disease (NAFLD) pathogenicity. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2023; 24:53. [DOI: 10.1186/s43042-023-00433-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 08/21/2023] [Indexed: 01/03/2025] Open
Abstract
Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease showing a rising prevalence globally. Genetic predisposition plays a key role in the development and progression of the disease pathogenicity.
Main body
This paper summarizes genetic associations based on their influence on several metabolic aspects such as lipid metabolism, glucose metabolism, hepatic iron accumulation and cholesterol metabolism toward the NAFLD pathogenicity. Furthermore, we present variations in some epigenetic characters and the microRNA profile with regard to NAFLD.
Conclusion
As reported in many studies, the PNPLA3 rs738409 variant seems to be significantly associated with NAFLD susceptibility. Other gene variants like TM6SF2 rs58542926, MBOAT7 rs641738 and GCKR variants also appear to be more prevalent among NAFLD patients. We believe these genetic variants may provide insights into new trends in developing noninvasive biomarkers and identify their suitability in clinical practice in the future.
Graphical abstract
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14
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Lv M, Zong C, Chen X, Lin X, Kong L, Li C. A cathodic photoelectrochemical biosensor based on CRISPR/Cas12a trans-cleavage mediated p-n heterojunction quenching mode for microRNA determination. Anal Chim Acta 2023; 1268:341399. [PMID: 37268340 DOI: 10.1016/j.aca.2023.341399] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 05/17/2023] [Accepted: 05/19/2023] [Indexed: 06/04/2023]
Abstract
In this study, a cathodic photoelectrochemical (PEC) bioanalysis for sensitive determination of microRNA (miRNA) has been constructed based on CRISPR/Cas12a trans-cleavage mediated [(C6)2Ir(dcbpy)]+PF6- (C6 represents coumarin-6 and dcbpy represents 4,4'-dicarboxyl-2,2'-bipyridine)-sensitized NiO photocathode and p-n heterojunction quenching mode. The [(C6)2Ir(dcbpy)]+PF6--sensitized NiO photocathode exhibits a stable and dramatically improved photocurrent signal due to highly effective photosensitization of [(C6)2Ir(dcbpy)]+ PF6-. Then Bi2S3 quantum dots (Bi2S3 QDs) is captured on the photocathode, resulting in markedly quenching of the photocurrent. When target miRNA is specifically recognized by the hairpin DNA to stimulate the trans-cleavage activity of CRISPR/Cas12a, leading to the leave of the Bi2S3 QDs. The photocurrent is gradually recovered with the increasing target concentration. Thus, the quantitative signal response to target is achieved. Benefiting from excellent performance of NiO photocathode, intense quenching effect of p-n heterojunction and accurate recognition ability of CRISPR/Cas12a, the cathodic PEC biosensor shows a wider linear range over 0.1 fM-10 nM, with a low detection limit of 36 aM. Also, the biosensor exhibits satisfying stability and selectivity.
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Affiliation(s)
- Mengwei Lv
- Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE, Key Laboratory of Analytical Chemistry for Life Science in Universities of Shandong, Qingdao University of Science and Technology, Qingdao, 266042, PR China
| | - Chengxue Zong
- Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE, Key Laboratory of Analytical Chemistry for Life Science in Universities of Shandong, Qingdao University of Science and Technology, Qingdao, 266042, PR China
| | - Xiaodong Chen
- Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE, Key Laboratory of Analytical Chemistry for Life Science in Universities of Shandong, Qingdao University of Science and Technology, Qingdao, 266042, PR China
| | - Xiaojia Lin
- Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE, Key Laboratory of Analytical Chemistry for Life Science in Universities of Shandong, Qingdao University of Science and Technology, Qingdao, 266042, PR China
| | - Linghui Kong
- Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE, Key Laboratory of Analytical Chemistry for Life Science in Universities of Shandong, Qingdao University of Science and Technology, Qingdao, 266042, PR China
| | - Chunxiang Li
- Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE, Key Laboratory of Analytical Chemistry for Life Science in Universities of Shandong, Qingdao University of Science and Technology, Qingdao, 266042, PR China.
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15
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Paluschinski M, Kordes C, Vucur M, Buettner V, Roderburg C, Xu HC, Shinte PV, Lang PA, Luedde T, Castoldi M. Differential Modulation of miR-122 Transcription by TGFβ1/BMP6: Implications for Nonresolving Inflammation and Hepatocarcinogenesis. Cells 2023; 12:1955. [PMID: 37566034 PMCID: PMC10416984 DOI: 10.3390/cells12151955] [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: 06/30/2023] [Revised: 07/24/2023] [Accepted: 07/26/2023] [Indexed: 08/12/2023] Open
Abstract
Chronic inflammation is widely recognized as a significant factor that promotes and worsens the development of malignancies, including hepatocellular carcinoma. This study aimed to explore the potential role of microRNAs in inflammation-associated nonresolving hepatocarcinogenesis. By conducting a comprehensive analysis of altered microRNAs in animal models with liver cancer of various etiologies, we identified miR-122 as the most significantly downregulated microRNA in the liver of animals with inflammation-associated liver cancer. Although previous research has indicated the importance of miR-122 in maintaining hepatocyte function, its specific role as either the trigger or the consequence of underlying diseases remains unclear. Through extensive analysis of animals and in vitro models, we have successfully demonstrated that miR-122 transcription is differentially regulated by the immunoregulatory cytokines, by the transforming growth factor-beta 1 (TGFβ1), and the bone morphogenetic protein-6 (BMP6). Furthermore, we presented convincing evidence directly linking reduced miR-122 transcription to inflammation and in chronic liver diseases. The results of this study strongly suggest that prolonged activation of pro-inflammatory signaling pathways, leading to disruption of cytokine-mediated regulation of miR-122, may significantly contribute to the onset and exacerbation of chronic liver disease.
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Affiliation(s)
- Martha Paluschinski
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, University Hospital, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany; (M.P.); (C.K.); (M.V.); (V.B.); (C.R.); (T.L.)
| | - Claus Kordes
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, University Hospital, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany; (M.P.); (C.K.); (M.V.); (V.B.); (C.R.); (T.L.)
| | - Mihael Vucur
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, University Hospital, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany; (M.P.); (C.K.); (M.V.); (V.B.); (C.R.); (T.L.)
| | - Veronika Buettner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, University Hospital, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany; (M.P.); (C.K.); (M.V.); (V.B.); (C.R.); (T.L.)
| | - Christoph Roderburg
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, University Hospital, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany; (M.P.); (C.K.); (M.V.); (V.B.); (C.R.); (T.L.)
| | - Haifeng C. Xu
- Institute for Molecular Medicine II, Medical Faculty, Heinrich-Heine University Hospital, 40225 Dusseldorf, Germany; (H.C.X.); (P.V.S.); (P.A.L.)
| | - Prashant V. Shinte
- Institute for Molecular Medicine II, Medical Faculty, Heinrich-Heine University Hospital, 40225 Dusseldorf, Germany; (H.C.X.); (P.V.S.); (P.A.L.)
| | - Philipp A. Lang
- Institute for Molecular Medicine II, Medical Faculty, Heinrich-Heine University Hospital, 40225 Dusseldorf, Germany; (H.C.X.); (P.V.S.); (P.A.L.)
| | - Tom Luedde
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, University Hospital, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany; (M.P.); (C.K.); (M.V.); (V.B.); (C.R.); (T.L.)
| | - Mirco Castoldi
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, University Hospital, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany; (M.P.); (C.K.); (M.V.); (V.B.); (C.R.); (T.L.)
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16
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Lucarini V, Nardozi D, Angiolini V, Benvenuto M, Focaccetti C, Carrano R, Besharat ZM, Bei R, Masuelli L. Tumor Microenvironment Remodeling in Gastrointestinal Cancer: Role of miRNAs as Biomarkers of Tumor Invasion. Biomedicines 2023; 11:1761. [PMID: 37371856 DOI: 10.3390/biomedicines11061761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/13/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open
Abstract
Gastrointestinal (GI) cancers are the most frequent neoplasm, responsible for half of all cancer-related deaths. Metastasis is the leading cause of death from GI cancer; thus, studying the processes that regulate cancer cell migration is of paramount importance for the development of new therapeutic strategies. In this review, we summarize the mechanisms adopted by cancer cells to promote cell migration and the subsequent metastasis formation by highlighting the key role that tumor microenvironment components play in deregulating cellular pathways involved in these processes. We, therefore, provide an overview of the role of different microRNAs in promoting tumor metastasis and their role as potential biomarkers for the prognosis, monitoring, and diagnosis of GI cancer patients. Finally, we relate the possible use of nutraceuticals as a new strategy for targeting numerous microRNAs and different pathways involved in GI tumor invasiveness.
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Affiliation(s)
- Valeria Lucarini
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
| | - Daniela Nardozi
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Valentina Angiolini
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
| | - Monica Benvenuto
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
- Departmental Faculty of Medicine and Surgery, Saint Camillus International University of Health and Medical Sciences, via di Sant'Alessandro 8, 00131 Rome, Italy
| | - Chiara Focaccetti
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Raffaele Carrano
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Zein Mersini Besharat
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
| | - Roberto Bei
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Laura Masuelli
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
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17
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Zeid D, Gould TJ. Chronic nicotine exposure alters sperm small RNA content in C57BL/6J mouse model. Dev Psychobiol 2023; 65:e22367. [PMID: 36811365 PMCID: PMC9978956 DOI: 10.1002/dev.22367] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 11/10/2022] [Accepted: 12/19/2022] [Indexed: 01/15/2023]
Abstract
Multigenerational inheritance is a nongenomic form of heritability characterized by altered phenotypes in the first generation born from the exposed parent. Multigenerational factors may account for inconsistencies and gaps in heritable nicotine addiction vulnerability. Our lab previously found that F1 offspring of male C57BL/6J mice chronically exposed to nicotine exhibited altered hippocampus functioning and related learning, nicotine-seeking, nicotine metabolism, and basal stress hormones. In an effort to identify germline mechanisms underlying these multigenerational phenotypes, the current study sequenced small RNA extracted from sperm of males chronically administered nicotine using our previously established exposure model. We identified 16 miRNAs whose expression in sperm was dysregulated by nicotine exposure. A literature review of previous research on these transcripts suggested an enrichment for regulation of psychological stress and learning. mRNAs predicted to be regulated by differentially expressed sperm small RNAs were further analyzed using exploratory enrichment analysis, which suggested potential modulation of pathways related to learning, estrogen signaling, and hepatic disease, among other findings. Overall, our findings point to links between nicotine-exposed F0 sperm miRNA and altered F1 phenotypes in this multigenerational inheritance model, particularly F1 memory, stress, and nicotine metabolism. These findings provide a valuable foundation for future functional validation of these hypotheses and characterization of mechanisms underlying male-line multigenerational inheritance.
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Affiliation(s)
- Dana Zeid
- Department of Psychology, Temple University, Philadelphia PA, USA
| | - Thomas J. Gould
- Department of Biobehavioral Health, Penn State University, University Park PA, USA
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18
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Costafreda MI, Sauleda S, Riveiro-Barciela M, Rico A, Llorens-Revull M, Guix S, Pintó RM, Bosch A, Rodríguez-Frías F, Rando A, Piron M, Bes M. Specific Plasma MicroRNA Signatures Underlying the Clinical Outcomes of Hepatitis E Virus Infection. Microbiol Spectr 2023; 11:e0466422. [PMID: 36695578 PMCID: PMC9927377 DOI: 10.1128/spectrum.04664-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 01/11/2023] [Indexed: 01/26/2023] Open
Abstract
The pathogenic mechanisms determining the diverse clinical outcomes of HEV infection (e.g., self-limiting versus chronic or symptomatic versus asymptomatic) are not yet understood. Because specific microRNA signatures during viral infection inform the cellular processes involved in virus replication and pathogenesis, we investigated plasma microRNA profiles in 44 subjects, including patients with symptomatic acute (AHE, n = 7) and chronic (CHE, n = 6) hepatitis E, blood donors with asymptomatic infection (HEV BDs, n = 9), and anti-HEV IgG+ IgM- (exposed BDs, n = 10) and anti-HEV IgG- IgM- (naive BDs, n = 12) healthy blood donors. By measuring the abundance of 179 microRNAs in AHE patients and naive BDs by reverse transcription-quantitative PCR (RT-qPCR), we identified 51 potential HEV-regulated microRNAs (P value adjusted for multiple testing by the Benjamini-Hochberg correction [PBH] < 0.05). Further analysis showed that HEV genotype 3 infection is associated with miR-122, miR-194, miR-885, and miR-30a upregulation and miR-221, miR-223, and miR-27a downregulation. AHE patients showed significantly higher levels of miR-122 and miR-194 and lower levels of miR-221, miR-27a, and miR-335 than HEV BDs. This specific microRNA signature in AHE could promote virus replication and reduce antiviral immune responses, contributing to the development of clinical symptoms. We found that miR-194, miR-335, and miR-221 can discriminate between asymptomatic HEV infections and those developing acute symptoms, whereas miR-335 correctly classifies AHE and CHE patients. Our data suggest that diverse outcomes of HEV infection result from different HEV-induced microRNA dysregulations. The specific microRNA signatures described offer novel information that may serve to develop biomarkers of HEV infection outcomes and improve our understanding of HEV pathogenesis, which may facilitate the identification of antiviral targets. IMPORTANCE There is increasing evidence that viruses dysregulate the expression and/or secretion of microRNAs to promote viral replication, immune evasion, and pathogenesis. In this study, we evaluated the change in microRNA abundance in patients with acute or chronic HEV infection and asymptomatic HEV-infected blood donors. Our results suggest that different HEV-induced microRNA dysregulations may contribute to the diverse clinical manifestations of HEV infection. The specific microRNA signatures identified in this study hold potential as predictive markers of HEV infection outcomes, which would improve the clinical management of hepatitis E patients, particularly of those developing severe symptoms or chronic infections. Furthermore, this study provides new insights into HEV pathogenesis that may serve to identify antiviral targets, which would have a major impact because no effective treatments are yet available.
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Affiliation(s)
- Maria I. Costafreda
- Blood and Tissue Bank of Catalonia (Banc de Sang i Teixits de Catalunya), Transfusion Safety Laboratory, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREhd), Instituto de Salud Carlos III, Madrid, Spain
- Vall d’Hebron Institute of Research (VHIR), Vall d’Hebron Universitary Hospital, Barcelona, Spain
- Enteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Safety, University of Barcelona, Barcelona, Spain
| | - Silvia Sauleda
- Blood and Tissue Bank of Catalonia (Banc de Sang i Teixits de Catalunya), Transfusion Safety Laboratory, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREhd), Instituto de Salud Carlos III, Madrid, Spain
- Vall d’Hebron Institute of Research (VHIR), Vall d’Hebron Universitary Hospital, Barcelona, Spain
| | - Mar Riveiro-Barciela
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREhd), Instituto de Salud Carlos III, Madrid, Spain
- Liver Unit, Internal Medicine Department, Vall d’Hebron Universitary Hospital and Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Angie Rico
- Blood and Tissue Bank of Catalonia (Banc de Sang i Teixits de Catalunya), Transfusion Safety Laboratory, Barcelona, Spain
| | - Meritxell Llorens-Revull
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREhd), Instituto de Salud Carlos III, Madrid, Spain
- Vall d’Hebron Institute of Research (VHIR), Vall d’Hebron Universitary Hospital, Barcelona, Spain
| | - Susana Guix
- Enteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Safety, University of Barcelona, Barcelona, Spain
| | - Rosa M. Pintó
- Enteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Safety, University of Barcelona, Barcelona, Spain
| | - Albert Bosch
- Enteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Safety, University of Barcelona, Barcelona, Spain
| | - Francisco Rodríguez-Frías
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREhd), Instituto de Salud Carlos III, Madrid, Spain
- Liver Pathology Laboratory, Microbiology and Biochemistry Department, Vall d’Hebron Clinical Laboratories, Vall d’Hebron Universitary Hospital, Barcelona, Spain
| | - Ariadna Rando
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREhd), Instituto de Salud Carlos III, Madrid, Spain
- Liver Pathology Laboratory, Microbiology and Biochemistry Department, Vall d’Hebron Clinical Laboratories, Vall d’Hebron Universitary Hospital, Barcelona, Spain
| | - Maria Piron
- Blood and Tissue Bank of Catalonia (Banc de Sang i Teixits de Catalunya), Transfusion Safety Laboratory, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREhd), Instituto de Salud Carlos III, Madrid, Spain
- Vall d’Hebron Institute of Research (VHIR), Vall d’Hebron Universitary Hospital, Barcelona, Spain
| | - Marta Bes
- Blood and Tissue Bank of Catalonia (Banc de Sang i Teixits de Catalunya), Transfusion Safety Laboratory, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREhd), Instituto de Salud Carlos III, Madrid, Spain
- Vall d’Hebron Institute of Research (VHIR), Vall d’Hebron Universitary Hospital, Barcelona, Spain
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19
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Park I, Kim N, Lee S, Park K, Son MY, Cho HS, Kim DS. Characterization of signature trends across the spectrum of non-alcoholic fatty liver disease using deep learning method. Life Sci 2023; 314:121195. [PMID: 36436619 DOI: 10.1016/j.lfs.2022.121195] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 11/02/2022] [Accepted: 11/11/2022] [Indexed: 11/26/2022]
Abstract
AIMS The timely diagnosis of different stages in NAFLD is crucial for disease treatment and reversal. We used hepatocellular ballooning to determine different NAFLD stages. MAIN METHODS We analyzed differentially expressed genes (DEGs) in 78 patients with NAFLD and in healthy controls from previously published RNA-seq data. We identified two expression types in NAFLD progression, calculated the predictive power of candidate genes, and validated them in an independent cohort. We also performed cancer studies with these candidates retrieved from the Cancer Genome Atlas. KEY FINDINGS We identified 103 DEGs in NAFLD patients compared to healthy controls: 75 genes gradually increased or decreased in the NAFLD stage, whereas 28 genes showed differences only in NASH. The former were enriched in negative regulation and binding-related genes; the latter were involved in positive regulation and cell proliferation. Feature selection showed the gradual up- or down-regulation of 21 genes in NASH compared to controls; 18 were highly expressed only in NASH. Using deep-learning method with subset of features from lasso regression, we obtained reliable determination performance in NAFL and NASH (accuracy: 0.857) and validated these genes using an independent cohort (accuracy: 0.805). From cancer studies, we identified significant differential expression of several candidate genes in LIHC; 5 genes were gradually up-regulated and 6 showing high expression only in NASH were influential to patient survival. SIGNIFICANCE The identified biomolecular signatures may determine the spectrum of NAFLD and its relationship with HCC, improving clinical diagnosis and prognosis and enabling a therapeutic intervention for NAFLD.
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Affiliation(s)
- Ilkyu Park
- Department of Bioinformatics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, 34113 Daejeon, Republic of Korea; Department of Environmental Disease Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, 34141 Daejeon, Republic of Korea
| | - Nakyoung Kim
- Department of Bioinformatics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, 34113 Daejeon, Republic of Korea; Department of Environmental Disease Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, 34141 Daejeon, Republic of Korea
| | - Sugi Lee
- Department of Environmental Disease Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, 34141 Daejeon, Republic of Korea
| | - Kunhyang Park
- Department of Core Facility Management Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141,Republic of Korea
| | - Mi-Young Son
- Department of Stem Cell Convergence Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, 34141 Daejeon, Republic of Korea.
| | - Hyun-Soo Cho
- Department of Stem Cell Convergence Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, 34141 Daejeon, Republic of Korea.
| | - Dae-Soo Kim
- Department of Bioinformatics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, 34113 Daejeon, Republic of Korea; Department of Environmental Disease Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, 34141 Daejeon, Republic of Korea.
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20
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Zhan Y, Zhang R, Guo Y, Cao S, Chen G, Tian B. Recent advances in tumor biomarker detection by lanthanide upconversion nanoparticles. J Mater Chem B 2023; 11:755-771. [PMID: 36606393 DOI: 10.1039/d2tb02017c] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Early tumor diagnosis could reliably predict the behavior of tumors and significantly reduce their mortality. Due to the response to early cancerous changes at the molecular or cellular level, tumor biomarkers, including small molecules, proteins, nucleic acids, exosomes, and circulating tumor cells, have been employed as powerful tools for early cancer diagnosis. Therefore, exploring new approaches to detect tumor biomarkers has attracted a great deal of research interest. Lanthanide upconversion nanoparticles (UCNPs) provide numerous opportunities for bioanalytical applications. When excited by low-energy near-infrared light, UCNPs exhibit several unique properties, such as large anti-Stoke shifts, sharp emission lines, long luminescence lifetimes, resistance to photobleaching, and the absence of autofluorescence. Based on these excellent properties, UCNPs have demonstrated great sensitivity and selectivity in detecting tumor biomarkers. In this review, an overview of recent advances in tumor biomarker detection using UCNPs has been presented. The key aspects of this review include detection mechanisms, applications in vitro and in vivo, challenges, and perspectives of UCNP-based tumor biomarker detection.
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Affiliation(s)
- Ying Zhan
- Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai 200444, China.
| | - Runchi Zhang
- Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai 200444, China.
| | - Yi Guo
- Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai 200444, China.
| | - Siyu Cao
- Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai 200444, China.
| | - Guifang Chen
- Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai 200444, China.
| | - Bo Tian
- Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai 200444, China.
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21
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Luo Y, Peng L, Shan W, Sun M, Luo L, Liang W. Machine learning in the development of targeting microRNAs in human disease. Front Genet 2023; 13:1088189. [PMID: 36685965 PMCID: PMC9845262 DOI: 10.3389/fgene.2022.1088189] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 12/12/2022] [Indexed: 01/05/2023] Open
Abstract
A microRNA is a small, single-stranded, non-coding ribonucleic acid that plays a crucial role in RNA silencing and can regulate gene expression. With the in-depth study of miRNA in development and disease, miRNA has become an attractive target for novel therapeutic strategies. Exploring miRNA targeting therapy only through experiments is expensive and laborious, so it is essential to develop novel and efficient computational methods to narrow down the search. Recent advances in machine learning applied in biomedical informatics provide opportunities to explore miRNA-targeting drugs, thus promoting miRNA therapeutics. This review provides an overview of recent advancements in miRNA targeting therapeutic using machine learning. First, we mainly describe the basics of predicting miRNA targeting drugs, including pharmacogenomic data resources and data preprocessing. Then we present primary machine learning algorithms and elaborate their application in discovering relationships among miRNAs, drugs, and diseases. Along with the progress of miRNA targeting therapeutics, we finally analyze and discuss the current challenges and opportunities that machine learning confronts.
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Affiliation(s)
- Yuxun Luo
- School of Computer Science and Engineering, Hunan University of Science and Technology, Xiangtan, China,Hunan Key Laboratory for Service computing and Novel Software Technology, Xiangtan, China
| | - Li Peng
- School of Computer Science and Engineering, Hunan University of Science and Technology, Xiangtan, China,Hunan Key Laboratory for Service computing and Novel Software Technology, Xiangtan, China
| | - Wenyu Shan
- School of Computer Science, University of South China, Hengyang, China
| | - Mengyue Sun
- School of Polymer Science and Polymer Engineering, The University of Akron, Akron, OH, United States
| | - Lingyun Luo
- School of Computer Science, University of South China, Hengyang, China
| | - Wei Liang
- School of Computer Science and Engineering, Hunan University of Science and Technology, Xiangtan, China,Hunan Key Laboratory for Service computing and Novel Software Technology, Xiangtan, China,*Correspondence: Wei Liang,
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22
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Shahiwala AF, Khan GA. Potential Phytochemicals for Prevention of Familial Breast Cancer with BRCA Mutations. Curr Drug Targets 2023; 24:521-531. [PMID: 36918779 DOI: 10.2174/1389450124666230314110800] [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: 06/08/2022] [Revised: 10/17/2022] [Accepted: 01/12/2023] [Indexed: 03/16/2023]
Abstract
Breast cancer has remained a global challenge and the second leading cause of cancer mortality in women and family history. Hereditary factors are some of the major risk factors associated with breast cancer. Out of total breast cancer cases, 5-10% account only for familial breast cancer, and nearly 50% of all hereditary breast cancer are due to BRCA1/BRCA2 germline mutations. BRCA1/2 mutations play an important role not only in determining the clinical prognosis of breast cancer but also in the survival curves. Since this risk factor is known, a significant amount of the healthcare burden can be reduced by taking preventive measures among people with a known history of familial breast cancer. There is increasing evidence that phytochemicals of nutrients and supplements help in the prevention and cure of BRCA-related cancers by different mechanisms such as limiting DNA damage, altering estrogen metabolism, or upregulating expression of the normal BRCA allele, and ultimately enhancing DNA repair. This manuscript reviews different approaches used to identify potential phytochemicals to mitigate the risk of familial breast cancer with BRCA mutations. The findings of this review can be extended for the prevention and cure of any BRCAmutated cancer after proper experimental and clinical validation of the data.
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Affiliation(s)
| | - Gazala Afreen Khan
- Department of Clinical Pharmacy & Pharmacotherapeutics, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
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23
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Hino K, Yanatori I, Hara Y, Nishina S. Iron and liver cancer: an inseparable connection. FEBS J 2022; 289:7810-7829. [PMID: 34543507 DOI: 10.1111/febs.16208] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 08/17/2021] [Accepted: 09/17/2021] [Indexed: 02/06/2023]
Abstract
Iron is an essential element for all organisms. Iron-containing proteins play critical roles in cellular functions. The biological importance of iron is largely attributable to its chemical properties as a transitional metal. However, an excess of 'free' reactive iron damages the macromolecular components of cells and cellular DNA through the production of harmful free radicals. On the contrary, most of the body's excess iron is stored in the liver. Not only hereditary haemochromatosis but also some liver diseases with mild-to-moderate hepatic iron accumulation, such as chronic hepatitis C, alcoholic liver disease and nonalcoholic steatohepatitis, are associated with a high risk for liver cancer development. These findings have attracted attention to the causative and promotive roles of iron in the development of liver cancer. In the last decade, accumulating evidence regarding molecules regulating iron metabolism or iron-related cell death programmes such as ferroptosis has shed light on the relationship between hepatic iron accumulation and hepatocarcinogenesis. In this review, we briefly present the current molecular understanding of iron regulation in the liver. Next, we describe the mechanisms underlying dysregulated iron metabolism depending on the aetiology of liver diseases. Finally, we discuss the causative and promotive roles of iron in cancer development.
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Affiliation(s)
- Keisuke Hino
- Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan
| | - Izumi Yanatori
- Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Japan
| | - Yuichi Hara
- Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan
| | - Sohji Nishina
- Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan
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24
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Yang K, Liu J, Gong Y, Li Y, Liu Q. Bioinformatics and systems biology approaches to identify molecular targeting mechanism influenced by COVID-19 on heart failure. Front Immunol 2022; 13:1052850. [DOI: 10.3389/fimmu.2022.1052850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 10/25/2022] [Indexed: 11/09/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a contemporary hazard to people. It has been known that COVID-19 can both induce heart failure (HF) and raise the risk of patient mortality. However, the mechanism underlying the association between COVID-19 and HF remains unclear. The common molecular pathways between COVID-19 and HF were identified using bioinformatic and systems biology techniques. Transcriptome analysis was performed to identify differentially expressed genes (DEGs). To identify gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways, common DEGs were used for enrichment analysis. The results showed that COVID-19 and HF have several common immune mechanisms, including differentiation of T helper (Th) 1, Th 2, Th 17 cells; activation of lymphocytes; and binding of major histocompatibility complex class I and II protein complexes. Furthermore, a protein-protein interaction network was constructed to identify hub genes, and immune cell infiltration analysis was performed. Six hub genes (FCGR3A, CD69, IFNG, CCR7, CCL5, and CCL4) were closely associated with COVID-19 and HF. These targets were associated with immune cells (central memory CD8 T cells, T follicular helper cells, regulatory T cells, myeloid-derived suppressor cells, plasmacytoid dendritic cells, macrophages, eosinophils, and neutrophils). Additionally, transcription factors, microRNAs, drugs, and chemicals that are closely associated with COVID-19 and HF were identified through the interaction network.
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25
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Rusu I, Pirlog R, Chiroi P, Nutu A, Puia VR, Fetti AC, Rusu DR, Berindan-Neagoe I, Al Hajjar N. The Implications of Noncoding RNAs in the Evolution and Progression of Nonalcoholic Fatty Liver Disease (NAFLD)-Related HCC. Int J Mol Sci 2022; 23:12370. [PMID: 36293225 PMCID: PMC9603983 DOI: 10.3390/ijms232012370] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 10/12/2022] [Accepted: 10/13/2022] [Indexed: 11/07/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver pathology worldwide. Meanwhile, liver cancer represents the sixth most common malignancy, with hepatocellular carcinoma (HCC) as the primary, most prevalent subtype. Due to the rising incidence of metabolic disorders, NAFLD has become one of the main contributing factors to HCC development. However, although NAFLD might account for about a fourth of HCC cases, there is currently a significant gap in HCC surveillance protocols regarding noncirrhotic NAFLD patients, so the majority of NAFLD-related HCC cases were diagnosed in late stages when survival chances are minimal. However, in the past decade, the focus in cancer genomics has shifted towards the noncoding part of the genome, especially on the microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), which have proved to be involved in the regulation of several malignant processes. This review aims to summarize the current knowledge regarding some of the main dysregulated, noncoding RNAs (ncRNAs) and their implications for NAFLD and HCC development. A central focus of the review is on miRNA and lncRNAs that can influence the progression of NAFLD towards HCC and how they can be used as potential screening tools and future therapeutic targets.
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Affiliation(s)
- Ioana Rusu
- Department of Pathology, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
- 3rd Department of General Surgery, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400186 Cluj-Napoca, Romania
| | - Radu Pirlog
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
| | - Paul Chiroi
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
| | - Andreea Nutu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
| | - Vlad Radu Puia
- 3rd Department of General Surgery, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400186 Cluj-Napoca, Romania
- Department of Surgery, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Alin Cornel Fetti
- 3rd Department of General Surgery, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400186 Cluj-Napoca, Romania
- Department of Surgery, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Daniel Radu Rusu
- Department of Pathology, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Ioana Berindan-Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
| | - Nadim Al Hajjar
- 3rd Department of General Surgery, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400186 Cluj-Napoca, Romania
- Department of Surgery, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
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26
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Gaber DA, Shaker O, Younis AT, El-Kassas M. LncRNA HULC and miR-122 Expression Pattern in HCC-Related HCV Egyptian Patients. Genes (Basel) 2022; 13:1669. [PMID: 36140836 PMCID: PMC9498747 DOI: 10.3390/genes13091669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 09/09/2022] [Accepted: 09/15/2022] [Indexed: 11/27/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly prevalent malignancy. It is a common type of cancer in Egypt due to chronic virus C infection (HCV). Currently, the frequently used lab test is serum α-fetoprotein. However, its diagnostic value is challenging due to its low sensitivity and specificity. Genetic biomarkers have recently provided new insights for cancer diagnostics. Herein, we quantified Lnc HULC and miR-122 gene expression to test their potential in diagnosis. Both biomarkers were tested in the sera of 60 HCC patients and 60 with chronic HCV using real-time RT-PCR. miR-122 was highly expressed in HCV patients with a significant difference from the HCC group (p = 0.004), which points towards its role in prognosis value as a predictor of HCC in patients with chronic HCV. HULC was more highly expressed in HCC patients than in the HCV group (p = 0.018), indicating its potential use in screening and the early diagnosis of HCC. The receiver operating characteristic (ROC) curve analysis showed their reliable sensitivity and specificity. Our results reveal that miR-122 can act as a prognostic tool for patients with chronic HCV. Furthermore, it is an early predictor of HCC. LncRNA HULC can be used as an early diagnostic tool for HCC.
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Affiliation(s)
- Dalia A. Gaber
- Medical Biochemistry & Molecular Biology Department, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
- College of Medicine, Gulf Medical University, Ajman 4184, United Arab Emirates
| | - Olfat Shaker
- Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Cairo University, Cairo 11956, Egypt
| | - Alaa Tarek Younis
- Medical Biochemistry & Molecular Biology Department, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
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27
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Wang L, Zhen H, Sun Y, Rong S, Li B, Song Z, Liu Z, Li Z, Ding J, Yang H, Zhang X, Sun H, Nie C. Plasma Exo-miRNAs Correlated with AD-Related Factors of Chinese Individuals Involved in Aβ Accumulation and Cognition Decline. Mol Neurobiol 2022; 59:6790-6804. [PMID: 36040555 PMCID: PMC9425792 DOI: 10.1007/s12035-022-03012-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 07/29/2022] [Indexed: 11/17/2022]
Abstract
Numerous studies have investigated the risk factors of Alzheimer’s disease (AD); however, AD-risk factors related miRNAs were rarely reported. In this study, AD-risk factor related miRNAs of 105 Chinese individuals (45 AD patients and 60 cognitively normal controls) were investigated. The results showed that Hsa-miR-185-5p, Hsa-miR-20a-5p, and Hsa-miR-497-5p were related to AD and education, Hsa-miR-185-5p, Hsa-miR-181c-5p, Hsa-miR-664a-3p, Hsa-miR-27a-3p, Hsa-miR-451a, and Hsa-miR-320a were related to AD and depression. Target prediction of above miRNAs showed that these miRNAs were involved in the generation and clearance of amyloid-beta (Aβ), important molecules related to cognition, and disease-activated microglia response to AD. It is worth noting that Hsa-miR-185-5p was related to both education and depression, whose decreased expression pattern in AD patients was alleviated by education and enhanced by depression, and participates in Aβ generation and accumulation. Our results indicated that certain education and depression factors can contribute to AD progression by modulating miRNA expression, implying that preventive interventions might alter AD progression in Chinese patients.
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Affiliation(s)
- Lifang Wang
- BGI-Shenzhen, Shenzhen, 518083, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China.,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Hefu Zhen
- BGI-Shenzhen, Shenzhen, 518083, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China.,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Yuzhe Sun
- BGI-Shenzhen, Shenzhen, 518083, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China.,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Shuang Rong
- Department of Nutrition and Food Hygiene, School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, China
| | - Benchao Li
- Department of Nutrition and Food Hygiene, School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, China
| | - Zhijie Song
- BGI-Shenzhen, Shenzhen, 518083, China.,James D. Watson Institute of Genome Sciences, Hangzhou, 310058, China
| | - Zhili Liu
- BGI-Shenzhen, Shenzhen, 518083, China.,James D. Watson Institute of Genome Sciences, Hangzhou, 310058, China
| | - Zhiming Li
- BGI-Shenzhen, Shenzhen, 518083, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China.,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Jiahong Ding
- BGI-Shenzhen, Shenzhen, 518083, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China.,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Huanming Yang
- BGI-Shenzhen, Shenzhen, 518083, China.,College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Xiuqing Zhang
- BGI-Shenzhen, Shenzhen, 518083, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China.,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Haixi Sun
- BGI-Shenzhen, Shenzhen, 518083, China. .,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China. .,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China. .,James D. Watson Institute of Genome Sciences, Hangzhou, 310058, China. .,BGI-Beijing, Beijing, 102601, China.
| | - Chao Nie
- BGI-Shenzhen, Shenzhen, 518083, China. .,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China. .,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China.
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28
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Chun KH. Molecular Targets and Signaling Pathways of microRNA-122 in Hepatocellular Carcinoma. Pharmaceutics 2022; 14:1380. [PMID: 35890276 PMCID: PMC9316959 DOI: 10.3390/pharmaceutics14071380] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 06/24/2022] [Accepted: 06/27/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading global causes of cancer mortality. MicroRNAs (miRNAs) are small interfering RNAs that alleviate the levels of protein expression by suppressing translation, inducing mRNA cleavage, and promoting mRNA degradation. miR-122 is the most abundant miRNA in the liver and is responsible for several liver-specific functions, including metabolism, cellular growth and differentiation, and hepatitis virus replication. Recent studies have shown that aberrant regulation of miR-122 is a key factor contributing to the development of HCC. In this review, the signaling pathways and the molecular targets of miR-122 involved in the progression of HCC have been summarized, and the importance of miR-122 in therapy has been discussed.
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Affiliation(s)
- Kwang-Hoon Chun
- Gachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, Incheon 21936, Korea
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29
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Orthologs of human circulating miRNAs associated with hepatocellular carcinoma are elevated in mouse plasma months before tumour detection. Sci Rep 2022; 12:10927. [PMID: 35764780 PMCID: PMC9240017 DOI: 10.1038/s41598-022-15061-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 06/17/2022] [Indexed: 11/08/2022] Open
Abstract
Research examining the potential for circulating miRNA to serve as markers for preneoplastic lesions or early-stage hepatocellular carcinoma (HCC) is hindered by the difficulties of obtaining samples from asymptomatic individuals. As a surrogate for human samples, we identified hub miRNAs in gene co-expression networks using HCC-bearing C3H mice. We confirmed 38 hub miRNAs as associated with HCC in F2 hybrid mice derived from radiogenic HCC susceptible and resistant founders. When compared to a panel of 12 circulating miRNAs associated with human HCC, two had no mouse ortholog and 7 of the remaining 10 miRNAs overlapped with the 38 mouse HCC hub miRNAs. Using small RNA sequencing data generated from serially collected plasma samples in F2 mice, we examined the temporal levels of these 7 circulating miRNAs and found that the levels of 4 human circulating markers, miR-122-5p, miR-100-5p, miR-34a-5p and miR-365-3p increased linearly as the time approaching HCC detection neared, suggesting a correlation of miRNA levels with oncogenic progression. Estimation of change points in the kinetics of the 4 circulating miRNAs suggested the changes started 17.5 to 6.8 months prior to HCC detection. These data establish these 4 circulating miRNAs as potential sentinels for preneoplastic lesions or early-stage HCC.
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Hepcidin in hepatocellular carcinoma. Br J Cancer 2022; 127:185-192. [PMID: 35264787 PMCID: PMC9296449 DOI: 10.1038/s41416-022-01753-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 01/26/2022] [Accepted: 02/09/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common reasons for cancer-related deaths. Excess iron increases HCC risk. Inevitably, hepcidin, the iron hormone that maintains systemic iron homoeostasis is involved in HCC pathology. Distinct from other cancers that show high hepcidin expression, HCC patients can show low hepcidin levels. Thus, it is of immense clinical benefit to address the regulation and action of hepcidin in HCC as this may help in identifying molecular targets for diagnosis, prognosis, and therapeutics. Accordingly, this review explores hepcidin in HCC. It presents the levels of tissue and serum hepcidin and explains the mechanisms that contribute to hepcidin reduction in HCC. These include downregulation of HAMP, TfR2, HJV, ALK2 and circular RNA circ_0004913, upregulation of matriptase-2 and GDF15, inactivation of RUNX3 and mutation in TP53. The enigmas around mir-122 and the functionalities of two major hepcidin inducers BMP6 and IL6 in relation to hepcidin in HCC are discussed. Effects of hepcidin downregulation are explained, specifically, increased cancer proliferation via activation of CDK1/STAT3 pathway and increased HCC risk due to reduction in a hepcidin-mediated protective effect against hepatic stellate cell activation. Hepcidin–ferroportin axis in HCC is addressed. Finally, the role of hepcidin in the diagnosis, prognosis and therapeutics of HCC is highlighted.
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31
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Javaid A, Zahra D, Rashid F, Mashraqi M, Alzamami A, Khurshid M, Ali Ashfaq U. Regulation of micro-RNA, epigenetic factor by natural products for the treatment of cancers: Mechanistic insight and translational Association. Saudi J Biol Sci 2022; 29:103255. [PMID: 35495735 PMCID: PMC9052154 DOI: 10.1016/j.sjbs.2022.03.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/26/2022] [Accepted: 03/02/2022] [Indexed: 02/07/2023] Open
Abstract
From onset to progression, cancer is a ailment that might take years to grow. All common epithelial malignancies, have a long latency period, frequently 20 years or more, different gene may contain uncountable mutations if they are clinically detectable. MicroRNAs (miRNAs) are around 22nt non-coding RNAs that control gene expression sequence-specifically through translational inhibition or messenger degradation of RNA (mRNA). Epigenetic processes of miRNA control genetic variants through genomic DNA methylation, post-translation histone modification, rework of the chromatin, and microRNAs. The field of miRNAs has opened a new era in understanding small non-coding RNAs since discovering their fundamental mechanisms of action. MiRNAs have been found in viruses, plants, and animals through molecular cloning and bioinformatics approaches. Phytochemicals can invert the epigenetic aberrations, a leading cause of the cancers of various organs, and act as an inhibitor of these changes. The advantage of phytochemicals is that they only function on cells that cause cancer without affecting normal cells. Phytochemicals appear to play a significant character in modulating miRNA expression, which is linked to variations in oncogenes, tumor suppressors, and cancer-derived protein production, according to several studies. In addition to standard anti-oxidant or anti-inflammatory properties, the initial epigenetic changes associated with cancer prevention may be modulated by many polyphenols. In correlation with miRNA and epigenetic factors to treat cancer some of the phytochemicals, including polyphenols, curcumin, resveratrol, indole-3-carbinol are studied in this article.
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Mariam A, Miller-Atkins G, Moro A, Rodarte AI, Siddiqi S, Acevedo-Moreno LA, Brown JM, Allende DS, Aucejo F, Rotroff DM. Salivary miRNAs as non-invasive biomarkers of hepatocellular carcinoma: a pilot study. PeerJ 2022; 10:e12715. [PMID: 35036096 PMCID: PMC8742548 DOI: 10.7717/peerj.12715] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 12/09/2021] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Improved detection of hepatocellular carcinoma (HCC) is needed, as current detection methods, such as alpha fetoprotein (AFP) and ultrasound, suffer from poor sensitivity. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate many cellular functions and impact cancer development and progression. Notably, miRNAs are detectable in saliva and have shown potential as non-invasive biomarkers for a number of cancers including breast, oral, and lung cancers. Here, we present, to our knowledge, the first report of salivary miRNAs in HCC and compare these findings to patients with cirrhosis, a high-risk cohort for HCC. METHODS We performed small RNA sequencing in 20 patients with HCC and 19 with cirrhosis. Eleven patients with HCC had chronic liver disease, and analyses were performed with these samples combined and stratified by the presence of chronic liver disease. P values were adjusted for multiple comparisons using a false discovery rate (FDR) approach and miRNA with FDR P < 0.05 were considered statistically significant. Differential expression of salivary miRNAs was compared to a previously published report of miRNAs in liver tissue of patients with HCC vs cirrhosis. Support vector machines and leave-one-out cross-validation were performed to determine if salivary miRNAs have predictive potential for detecting HCC. RESULTS A total of 4,565 precursor and mature miRNAs were detected in saliva and 365 were significantly different between those with HCC compared to cirrhosis (FDR P < 0.05). Interestingly, 283 of these miRNAs were significantly downregulated in patients with HCC. Machine-learning identified a combination of 10 miRNAs and covariates that accurately classified patients with HCC (AUC = 0.87). In addition, we identified three miRNAs that were differentially expressed in HCC saliva samples and in a previously published study of miRNAs in HCC tissue compared to cirrhotic liver tissue. CONCLUSIONS This study demonstrates, for the first time, that miRNAs relevant to HCC are detectable in saliva, that salivary miRNA signatures show potential to be highly sensitive and specific non-invasive biomarkers of HCC, and that additional studies utilizing larger cohorts are needed.
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Affiliation(s)
- Arshiya Mariam
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, United States
| | - Galen Miller-Atkins
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, United States
| | - Amika Moro
- Department of General Surgery, Cleveland Clinic, Cleveland, Ohio, United States
| | | | - Shirin Siddiqi
- Department of General Surgery, Cleveland Clinic, Cleveland, Ohio, United States
| | | | - J. Mark Brown
- Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, Ohio, United States
- Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio, United States
| | - Daniela S. Allende
- Department of Pathology, Cleveland Clinic, Cleveland, Ohio, United States
| | - Federico Aucejo
- Department of General Surgery, Cleveland Clinic, Cleveland, Ohio, United States
| | - Daniel M. Rotroff
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, United States
- Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, Ohio, United States
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Elghoroury EA, Abdelghaffar EE, Awadallah E, Kamel SA, Kandil D, Hassan EM, Hassan M, Kamel MM, Gomaa MM, Fathalla LA. Detection of exosomal miR-18a and miR-222 levels in Egyptian patients with hepatic cirrhosis and hepatocellular carcinoma. Int J Immunopathol Pharmacol 2022; 36:3946320221097832. [PMID: 35467432 PMCID: PMC9047801 DOI: 10.1177/03946320221097832] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is known to be the second leading cause of cancer-related mortality worldwide. For improving the prognosis as well as reducing the rate of mortality, early diagnosis of HCC is a must. AIMS This study was conducted to assess the ability of the serum expression of exosomal miR-18a and miR-222 to differentiate and diagnose patients with HCC, patients with liver cirrhosis, and healthy controls. METHODS This study included 51 patients with liver cirrhosis, 51 patients with HCC on top of hepatitis C virus (HCV) infection, and 50 healthy controls. RESULTS miR-18a and miR-222 were assessed using reverse transcription-polymerase chain reaction. MiR-18a and miR-222 levels were significantly higher in the liver cirrhosis and HCC groups than the control group (p ˂ 0.001). However, no statistically significant difference was found between patients with HCC and liver cirrhosis (p = 0.4 for miR-18a and p = 0.1 for miR-222). ROC curve analyses to evaluate the diagnostic performances of the two miRNAs as important noninvasive diagnostic markers revealed a best cutoff value of 2 for miR-18a to differentiate between liver cirrhosis, HCC, and healthy controls. And for mir-222, a cutoff value of 1.7 and 1.9 showed the highest specificity for discrimination between liver cirrhosis, HCC, and healthy controls, respectively. Moreover, logistic regression model revealed that miR-18a expression was independent predictive factor in HCC patients (p = 0.004), while miR-222 expression was independent predictive factor in liver cirrhosis patients (p < 0.001). CONCLUSION miR-18a and miR-222 were significantly discriminative markers between patients with liver cirrhosis and HCC and healthy individuals. Therefore, they have a prognostic rather than a diagnostic value. Moreover, miR-18a and miR-222 could be useful in identifying liver injuries, including fibrosis and cirrhosis.
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Affiliation(s)
- Eman A Elghoroury
- Clinical and Chemical Pathology Department, 68787National Research Centre, Dokki, Cairo, Egypt
| | - Esmat E Abdelghaffar
- Clinical and Chemical Pathology Department, 68787National Research Centre, Dokki, Cairo, Egypt
| | - Eman Awadallah
- Clinical and Chemical Pathology Department, 68787National Research Centre, Dokki, Cairo, Egypt
| | - Solaf A Kamel
- Clinical and Chemical Pathology Department, 68787National Research Centre, Dokki, Cairo, Egypt
| | - Dina Kandil
- Clinical and Chemical Pathology Department, 68787National Research Centre, Dokki, Cairo, Egypt
| | - Eman M Hassan
- Clinical and Chemical Pathology Department, 68787National Research Centre, Dokki, Cairo, Egypt
| | - Mirhane Hassan
- Clinical and Chemical Pathology Department, 68787National Research Centre, Dokki, Cairo, Egypt
| | - Mahmoud M Kamel
- Clinical and Chemical Pathology Department, 68804National Cancer Institute, Cairo University, Cairo, Egypt
| | - Mohammed M Gomaa
- Department of Diagnostic and Interventional Radiology, 68804National Cancer Institute, Cairo University, Cairo, Egypt
| | - Lamiaa A Fathalla
- Clinical and Chemical Pathology Department, 68804National Cancer Institute, Cairo University, Cairo, Egypt
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Abdelbaky I, Tayara H, Chong KT. Identification of miRNA-Small Molecule Associations by Continuous Feature Representation Using Auto-Encoders. Pharmaceutics 2021; 14:pharmaceutics14010003. [PMID: 35056899 PMCID: PMC8780428 DOI: 10.3390/pharmaceutics14010003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/17/2021] [Accepted: 12/18/2021] [Indexed: 12/17/2022] Open
Abstract
MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in the body and affect various diseases, including cancers. Controlling miRNAs with small molecules is studied herein to provide new drug repurposing perspectives for miRNA-related diseases. Experimental methods are time- and effort-consuming, so computational techniques have been applied, relying mostly on biological feature similarities and a network-based scheme to infer new miRNA–small molecule associations. Collecting such features is time-consuming and may be impractical. Here we suggest an alternative method of similarity calculation, representing miRNAs and small molecules through continuous feature representation. This representation is learned by the proposed deep learning auto-encoder architecture. Our suggested representation was compared to previous works and achieved comparable results using 5-fold cross validation (92% identified within top 25% predictions), and better predictions for most of the case studies (avg. of 31% vs. 25% identified within the top 25% of predictions). The results proved the effectiveness of our proposed method to replace previous time- and effort-consuming methods.
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Affiliation(s)
- Ibrahim Abdelbaky
- Artificial Intelligence Department, Faculty of Computers and Artificial Intelligence, Benha University, Banha 13518, Egypt;
| | - Hilal Tayara
- School of International Engineering and Science, Jeonbuk National University, Jeonju 54896, Korea
- Correspondence: (H.T.); (K.T.C.); Tel.: +82-63-270-2478 (K.T.C.)
| | - Kil To Chong
- Department of Electronics and Information Engineering, Jeonbuk National University, Jeonju 54896, Korea
- Advanced Electronics and Information Research Center, Jeonbuk National University, Jeonju 54896, Korea
- Correspondence: (H.T.); (K.T.C.); Tel.: +82-63-270-2478 (K.T.C.)
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35
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Dashti F, Mirazimi SMA, Rabiei N, Fathazam R, Rabiei N, Piroozmand H, Vosough M, Rahimian N, Hamblin MR, Mirzaei H. The role of non-coding RNAs in chemotherapy for gastrointestinal cancers. MOLECULAR THERAPY. NUCLEIC ACIDS 2021; 26:892-926. [PMID: 34760336 PMCID: PMC8551789 DOI: 10.1016/j.omtn.2021.10.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gastrointestinal (GI) cancers, including colorectal, gastric, hepatic, esophageal, and pancreatic tumors, are responsible for large numbers of deaths around the world. Chemotherapy is the most common approach used to treat advanced GI cancer. However, chemoresistance has emerged as a critical challenge that prevents successful tumor elimination, leading to metastasis and recurrence. Chemoresistance mechanisms are complex, and many factors and pathways are involved. Among these factors, non-coding RNAs (ncRNAs) are critical regulators of GI tumor development and subsequently can induce resistance to chemotherapy. This occurs because ncRNAs can target multiple signaling pathways, affect downstream genes, and modulate proliferation, apoptosis, tumor cell migration, and autophagy. ncRNAs can also induce cancer stem cell features and affect the epithelial-mesenchymal transition. Thus, ncRNAs could possibly act as new targets in chemotherapy combinations to treat GI cancer and to predict treatment response.
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Affiliation(s)
- Fatemeh Dashti
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Seyed Mohammad Ali Mirazimi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Nikta Rabiei
- School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Reza Fathazam
- School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Negin Rabiei
- School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Haleh Piroozmand
- Faculty of Veterinary Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Massoud Vosough
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Neda Rahimian
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Michael R. Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa
- Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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Samieri C, Yassine HN, Melo van Lent D, Lefèvre-Arbogast S, van de Rest O, Bowman GL, Scarmeas N. Personalized nutrition for dementia prevention. Alzheimers Dement 2021; 18:1424-1437. [PMID: 34757699 DOI: 10.1002/alz.12486] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 08/26/2021] [Accepted: 08/30/2021] [Indexed: 12/17/2022]
Abstract
The role of nutrition has been investigated for decades under the assumption of one-size-fits-all. Yet there is heterogeneity in metabolic and neurobiological responses to diet. Thus a more personalized approach may better fit biological reality and have increased efficacy to prevent dementia. Personalized nutrition builds on the food exposome, defined as the history of diet-related exposures over the lifetime, and on its interactions with the genome and other biological characteristics (eg, metabolism, the microbiome) to shape health. We review current advances of personalized nutrition in dementia research. We discuss key questions, success milestones, and future roadmap from observational epidemiology to clinical studies through basic science. A personalized nutrition approach based on the best prescription for the most appropriate target population in the most relevant time-window has the potential to strengthen dementia-prevention efforts.
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Affiliation(s)
- Cécilia Samieri
- Univ. Bordeaux, ISPED, Inserm, Bordeaux Population Health Research Center, Bordeaux, France
| | - Hussein N Yassine
- Department of Medicine, Keck School of Medicine USC, Los Angeles, California, USA.,Department of Neurology, Keck School of Medicine USC, Los Angeles, California, USA
| | - Debora Melo van Lent
- Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, Texas, USA.,Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA
| | | | - Ondine van de Rest
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, the Netherlands
| | - Gene L Bowman
- Department of Neurology and Layton Aging and Alzheimer's Disease Center, Oregon Health and Science University, Portland, Oregon, USA.,Helfgott Research Institute, National University of Natural Medicine, Portland, Oregon, USA
| | - Nikolaos Scarmeas
- 1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.,Taub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center, Department of Neurology, Columbia University, New York, New York, USA
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Sendi H, Yazdimamaghani M, Hu M, Sultanpuram N, Wang J, Moody AS, McCabe E, Zhang J, Graboski A, Li L, Rojas JD, Dayton PA, Huang L, Wang AZ. Nanoparticle delivery of miR-122 inhibits colorectal cancer liver metastasis. Cancer Res 2021; 82:105-113. [PMID: 34753773 DOI: 10.1158/0008-5472.can-21-2269] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 09/13/2021] [Accepted: 11/05/2021] [Indexed: 11/16/2022]
Abstract
Liver metastasis is a leading cause of cancer morbidity and mortality. Thus, there has been strong interest in the development of therapeutics that can effectively prevent liver metastasis. One potential strategy is to utilize molecules that have broad effects on the liver microenvironment, such as microRNA-122 (miR-122), a liver-specific microRNA (miRNA) that is a key regulator of diverse hepatic functions. Here we report the development of a nanoformulation miR-122 as a therapeutic agent for preventing liver metastasis. We engineered a galactose-targeted lipid calcium phosphate (Gal-LCP) nanoformulation of miR-122. This nanotherapeutic elicited no significant toxicity and delivered miR-122 into hepatocytes with specificity and high efficiency. Across multiple colorectal cancer (CRC) liver metastasis models, treatment with Gal-LCP miR-122 treatment effectively prevented CRC liver metastasis and prolonged survival. Mechanistic studies revealed that delivery of miR-122 was associated with downregulation of key genes in involved in metastatic and cancer inflammation pathways, including several pro-inflammatory factors, matrix metalloproteinases, and other extracellular matrix degradation enzymes. Moreover, Gal-LCP miR-122 treatment was associated with an increased CD8+/CD4+ T-cell ratio and decreased immunosuppressive cell infiltration, which makes the liver more conducive to anti-tumor immune response. Collectively, this work presents a strategy to improve cancer prevention and treatment with nanomedicine-based delivery of miRNA.
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Affiliation(s)
- Hossein Sendi
- Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, North Carolina
- Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina
- UNC School of Pharmacy, Chapel Hill, North Carolina
| | - Mostafa Yazdimamaghani
- Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina
- UNC School of Pharmacy, Chapel Hill, North Carolina
| | - Mengying Hu
- Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina
- UNC School of Pharmacy, Chapel Hill, North Carolina
| | - Nikhila Sultanpuram
- Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, North Carolina
- Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina
| | - Jie Wang
- Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, North Carolina
- Dalian Municipal Central Hospital, Dalian, China
| | - Amber S Moody
- UNC School of Pharmacy, Chapel Hill, North Carolina
- Joint Department of Biomedical Engineering, University of North Carolina and, North Carolina State University, Chapel Hill, North Carolina
| | - Ellie McCabe
- Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina
- UNC School of Pharmacy, Chapel Hill, North Carolina
| | - Jiajie Zhang
- Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, North Carolina
| | - Amanda Graboski
- Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, North Carolina
| | - Liantao Li
- Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, North Carolina
| | - Juan D Rojas
- Joint Department of Biomedical Engineering, University of North Carolina and, North Carolina State University, Chapel Hill, North Carolina
| | - Paul A Dayton
- UNC School of Pharmacy, Chapel Hill, North Carolina
- Joint Department of Biomedical Engineering, University of North Carolina and, North Carolina State University, Chapel Hill, North Carolina
| | - Leaf Huang
- Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina
- UNC School of Pharmacy, Chapel Hill, North Carolina
| | - Andrew Z Wang
- Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, North Carolina.
- Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina
- UNC School of Pharmacy, Chapel Hill, North Carolina
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
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Xu G, Bu S, Wang X, Ge H. MiR-122 radiosensitize hepatocellular carcinoma cells by suppressing cyclin G1. Int J Radiat Biol 2021; 98:11-17. [PMID: 34623217 DOI: 10.1080/09553002.2021.1987561] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
PURPOSE Emerging evidence has shown that radiotherapy is an effective treatment for hepatocellular carcinoma (HCC), Micro(mi)RNAs are involved in regulating radiosensitivity in many cancers. MiR-122 accounts for approximately 70% of all cloned miRNAs in the liver, but there are few reports about whether it is involved in regulating of radiosensitivity in HCC cells. MATERIALS AND METHODS HCC cells (HepG2 and Huh7) overexpressing miR-122 were constructed by transfecting them with lentiviral-miR-122. Then, their proliferation ability was analyzed by the MTT, and colony formation assays and a xenograft tumor model was used to detect their radiosensitivity. The expression of cyclin G1 mRNA and protein was detected by the quantitative real-time polymerase chain reaction and western blotting, respectively. RESULTS Overexpression of miR-122 inhibited the proliferation of, and radiosensitized HCC cells. Cyclin G1 mRNA and protein level were suppressed in HepG2 tumors overexpression miR-122. CONCLUSION MiR-122 may be useful as a potential radiosensitizer for HCC, and its mechanism is related to the regulation of cyclin G1.
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Affiliation(s)
- Gang Xu
- Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Shanshan Bu
- Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiushen Wang
- Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Hong Ge
- Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
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Thai SF, Jones CP, Robinette BL, Ren H, Vallant B, Fisher A, Kitchin KT. Effects of Copper Nanoparticles on mRNA and Small RNA Expression in Human Hepatocellular Carcinoma (HepG2) Cells. JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY 2021; 21:5083-5098. [PMID: 33875094 PMCID: PMC10803003 DOI: 10.1166/jnn.2021.19328] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
With the advancement of nanotechnology, nanoparticles are widely used in many different industrial processes and consumer products. Copper nanoparticles (Cu NPs) are among the most toxic nanomaterials. We investigated Cu NPs toxicity in Human Hepatocellular carcinoma (HepG2) cells by examining signaling pathways, and microRNA/mRNA interactions. We compared the effects of exposures to Cu NPs at various concentrations and CuCl₂ was used as a control. The number of differentially expressed mRNA did not follow a linear dose-response relationship for either Cu NPs or CuCl₂ treatments. The most significantly altered genes and pathways by Cu NPs exposure were NRF2 (nuclear factor erythroid 2 related factor 2)-mediated oxidative stress response, protein ubiquitination, Tumor protein p53 (p53), phase I and II metabolizing enzymes, antioxidant proteins and phase III detoxifying gene pathways.Messenger RNA-microRNA interaction from MicroRNA Target Filter Analyses revealed more signaling pathways altered in Cu NPs treated samples than transcriptomics alone, including cell proliferation, DNA methylation, endoplasmic reticulum (ER) stress, apoptosis, autophagy, reactive oxygen species, inflammation, tumorigenesis, extracellular matrix/angiogenesis and protein synthesis. In contrast, in the control (CuCl₂) treated samples showed mostly changes in inflammation mainly through regulation of the Nuclear Factor Kappa-light-chain-enhancer of Activated B-cells (NFκB). Further, some RNA based parameters that showed promise as biomarkers of Cu NPs exposure including both well and lesser known genes: heme oxygenase 1 (HMOX1), heat shock protein, c-Fos proto-oncogene, DNA methyltransferases, and glutamate-cysteine ligase modifier subunit (GCLM, part of the glutathione synthesis pathway). The differences in signaling pathways altered by the Cu NPs and CuCl₂ treatments suggest that the effects of the Cu NPs were not the results of nanomaterial dissolution to soluble copper ions.
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Affiliation(s)
- Sheau-Fung Thai
- Center for Computational Toxicology and Exposure, US Environmental Protection Agency, 109 TW Alexander Dr., Durham NC 27709, USA
| | - Carlton P Jones
- Center for Computational Toxicology and Exposure, US Environmental Protection Agency, 109 TW Alexander Dr., Durham NC 27709, USA
| | - Brian L Robinette
- Center for Computational Toxicology and Exposure, US Environmental Protection Agency, 109 TW Alexander Dr., Durham NC 27709, USA
| | - Hongzu Ren
- Center for Public Health and Environmental Assessment, US Environmental Production Agency, 109 TW Alexander Dr., Durham NC 27709, USA
| | - Beena Vallant
- Center for Computational Toxicology and Exposure, US Environmental Protection Agency, 109 TW Alexander Dr., Durham NC 27709, USA
| | - Anna Fisher
- Center for Public Health and Environmental Assessment, US Environmental Production Agency, 109 TW Alexander Dr., Durham NC 27709, USA
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ONAN E, AKKIZ H, SANDIKCI MU, ÜSKÜDAR O, ÖZTÜRK AB. Importance of circulating microRNA-122 for hepatocellular carcinoma. CUKUROVA MEDICAL JOURNAL 2021. [DOI: 10.17826/cumj.934776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Ali Beg MM, Guru SA, Abdullah SM, Ahmad I, Rizvi A, Akhter J, Goyal Y, Verma AK. Regulation of miR-126 and miR-122 Expression and Response of Imatinib Treatment on Its Expression in Chronic Myeloid Leukemia Patients. Oncol Res Treat 2021; 44:530-537. [PMID: 34515193 DOI: 10.1159/000518722] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 07/26/2021] [Indexed: 11/19/2022]
Abstract
BACKGROUND MicroRNAs (miRNAs) have been observed to exhibit altered expression patterns in chronic myeloid leukemia (CML). Therefore, this study was aimed to evaluate the clinical importance of miR-126 and miR-122 expression in concert to imatinib response in CML patients. METHODS The present study included 100 CML and 100 healthy subjects. The expression of the 2 miRNAs was performed using TaqMan probe chemistry, and snU6 was used as internal control. RESULTS The expression of miR-126 and miR-122 was downregulated in CML patients, with a mean fold change ± SD 0.20 ± 0.33 and 0.22 ± 0.37, respectively. While the expression of both miRNAs was analysed before and after imatinib treatment, it was observed that the expression levels of both were increased after imatinib treatment by 26.25-fold (5.33 against 0.20) and 13.95-fold (3.07 against 0.22) and the increase was statistically significant (p < 0.0001 and p < 0.0001, respectively). The expression of miR-126 was not conclusive when compared in different clinical stages of the CML disease as it showed a decreased expression in patients with accelerated phase compared to chronic phase (mean fold change = 0.03 and 0.27, respectively), but patients with chronic phase and blastic phase had comparable expression (mean fold change = 0.27 and 0.24, respectively). We also observed an increased expression of both miRNAs after imatinib therapy in each clinical phase. CONCLUSION The study concludes that expression of miR-126 and miR-122 increases after imatinib treatment in CML patients and that miR-126 defines the good responders of imatinib therapy.
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Affiliation(s)
- Mirza Masroor Ali Beg
- Department of Biochemistry, Faculty of Medicine, Alatoo International University, Bishkek, Kyrgyzstan
- Department of Medical Bitechnology, Yeungnam University, Gyeongsan, Republic of Korea
| | - Sameer Ahmad Guru
- Department of Medical Laboratory, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | | | - Irfan Ahmad
- Department of Clinical Laboratory Science, King Khalid University, Abha, Saudi Arabia
- Research Center for Advanced Materials Science, King Khalid University, Abha, Saudi Arabia
| | - Aliya Rizvi
- Department of Pathology, King George Medical University, Lucknow, India
| | - Juheb Akhter
- Department of Toxicology, Jamia Hamdard, New Delhi, India
| | - Yamini Goyal
- Department of Biotechnology, Jamia Millia Islamia, New Delhi, India
| | - Amit K Verma
- Department of Zoology and Environmental Sciences, GKV, Haridwar, India
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Chae YJ, Chang JE, Lee MK, Lim J, Shin KH, Lee KR. Regulation of drug transporters by microRNA and implications in disease treatment. JOURNAL OF PHARMACEUTICAL INVESTIGATION 2021. [DOI: 10.1007/s40005-021-00538-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Circular RNA Pleiotrophin promotes carcinogenesis in glioma via regulation of microRNA-122/SRY-box transcription factor 6 axis. Eur J Cancer Prev 2021; 29:165-173. [PMID: 31609809 DOI: 10.1097/cej.0000000000000535] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
BACKGROUND Circular RNAs (circRNAs) are recently identified as gene regulators in mammals and play important roles in carcinogenesis of cancer. For example, circRNA_PTN has been recognized as a biomarker of human cancer and is overexpressed in glioma. The molecular function of circRNA_PTN and its downstream targets in glioma, however, remains elusive. METHODS Quantitative polymerase chain reaction analysis was used to measure the expression of circular RNA pleiotrophin (circ_PTN) and miR-122. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, propidium iodide and Annexin-V/propidium iodide assay were performed to determine cell proliferation and apoptosis of glioma cells. Circular RNA Interactome and TargetScan were used to predict the potential microRNA targeting of circ_PTN and the potential targets of miR-122, respectively. Luciferase activity assay was used to validate these interactions. Downstream molecular mechanisms, including SRY-box transcription factor 6 (SOX6), extracellular regulated protein kinases (ERK), Cyclin D1, B-cell lymphoma-2 (BCL-2) and BCL2 associated X, apoptosis regulator (BAX), were determined by western blot. RESULTS Circ_PTN was overexpressed in glioma cells, and its knockdown induced cell proliferation inhibition, cell cycle arrest and apoptosis in glioma cells. The target microRNA of circ_PTN was predicted to be miR-122, the expression of which was negatively correlated with circ_PTN in glioma cells. Moreover, SOX6 was predicted as a potential target of miR-122, and miR-122 overexpression decreased SOX6 expression. MiR-122 inhibitor reversed the tumor-suppressing effects of circ_PTN knockdown, while overexpression of SOX6 impaired the miR-122 overexpression-induced cell growth inhibition and apoptosis. In addition, mitogen activated kinase-like protein (MAPK)/ERK pathway was involved in circ_PTN/miR-122/SOX6 axis. CONCLUSIONS Circ_PTN acted as a sponge of miR-122 and upregulated miR-122 target SOX6, thus promoting carcinogenesis of glioma cells.
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Wu J, Zhou X, Li P, Lin X, Wang J, Hu Z, Zhang P, Chen D, Cai H, Niessner R, Haisch C, Sun P, Zheng Y, Jiang Z, Zhou H. Ultrasensitive and Simultaneous SERS Detection of Multiplex MicroRNA Using Fractal Gold Nanotags for Early Diagnosis and Prognosis of Hepatocellular Carcinoma. Anal Chem 2021; 93:8799-8809. [PMID: 34076420 DOI: 10.1021/acs.analchem.1c00478] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Sensitive and simultaneous detection of multiple cancer-related biomarkers in serum is essential for diagnosis, therapy, prognosis, and staging of cancer. Herein, we proposed a magnetically assisted sandwich-type surface-enhanced Raman scattering (SERS)-based biosensor for ultrasensitive and multiplex detection of three hepatocellular carcinoma-related microRNA (miRNA) biomarkers. The biosensor consists of an SERS tag (probe DNA-conjugated DNA-engineered fractal gold nanoparticles, F-AuNPs) and a magnetic capture substrate (capture DNA-conjugated Ag-coated magnetic nanoparticles, AgMNPs). The proposed strategy achieved simultaneous and sensitive detection of three miRNAs (miRNA-122, miRNA-223, and miRNA-21), and the limits of detection of the three miRNAs in human serum are 349 aM for miRNA-122, 374 aM for miRNA-223, and 311 aM for miRNA-21. High selectivity and accuracy of the SERS biosensor were proved by practical analysis in human serum. Moreover, the biosensor exhibited good practicability in multiplex detection of three miRNAs in 92 clinical sera from AFP-negative patients, patients before and after hepatectomy, recurred and relapse-free patients after hepatectomy, and hepatocellular carcinoma patients at distinct Barcelona clinic liver cancer stages. The experiment results demonstrate that our SERS-based assay is a promising candidate in clinical application and exhibited potential for the prediction, diagnosis, monitoring, and staging of cancers.
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Affiliation(s)
- Jiamin Wu
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Xia Zhou
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Ping Li
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Xiaoling Lin
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Jinhua Wang
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Ziwei Hu
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Pengcheng Zhang
- College of Chemistry and Chemical Engineering, Zhoukou Normal University, Zhoukou, Henan 466000, China
| | - Dong Chen
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China
| | - Huaihong Cai
- College of Chemistry and Materials Science, Jinan University, Guangzhou, Guangdong 510632, China
| | - Reinhard Niessner
- Institute of Hydrochemistry and Chair for Analytical Chemistry, Technical University of Munich, Marchioninistr. 17, Munich D-81377, Germany
| | - Christoph Haisch
- Institute of Hydrochemistry and Chair for Analytical Chemistry, Technical University of Munich, Marchioninistr. 17, Munich D-81377, Germany
| | - Pinghua Sun
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Yun Zheng
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China
| | - Zhengjin Jiang
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Haibo Zhou
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
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Ghosh S, Kumar V, Mukherjee H, Lahiri D, Roy P. Nutraceutical regulation of miRNAs involved in neurodegenerative diseases and brain cancers. Heliyon 2021; 7:e07262. [PMID: 34195404 PMCID: PMC8225984 DOI: 10.1016/j.heliyon.2021.e07262] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 02/24/2021] [Accepted: 06/05/2021] [Indexed: 12/12/2022] Open
Abstract
The human brain is a well-connected, intricate network of neurons and supporting glial cells. Neurodegenerative diseases arise as a consequence of extensive loss of neuronal cells leading to disruption of their natural structure and function. On the contrary, rapid proliferation and growth of glial as well as neuronal cells account for the occurrence of malignancy in brain. In both cases, the molecular microenvironment holds pivotal importance in the progression of the disease. MicroRNAs (miRNA) are one of the major components of the molecular microenvironment. miRNAs are small, noncoding RNAs that control gene expression post-transcriptionally. As compared to other tissues, the brain expresses a substantially high number of miRNAs. In the early stage of neurodegeneration, miRNA expression upregulates, while in oncogenesis, miRNA expression is gradually lost. Neurodegeneration and brain cancer is presumed to be under the influence of identical pathways of cell proliferation, differentiation and cell death which are tightly regulated by miRNAs. It has been confirmed experimentally that miRNA expression can be regulated by nutraceuticals - macronutrients, micronutrients or natural products derived from food; thereby making dietary supplements immensely significant for targeting miRNAs having altered expression patterns during neurodegeneration or oncogenesis. In this review, we will discuss in detail, about the common miRNAs involved in brain cancers and neurodegenerative diseases along with the comprehensive list of miRNAs involved separately in both pathological conditions. We will also discuss the role of nutraceuticals in the regulation of those miRNAs which are involved in both of these pathological conditions.
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Affiliation(s)
- Souvik Ghosh
- Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247667, India
- Biomaterials and Multiscale Mechanics Laboratory, Department of Metallurgical and Materials Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247667, India
- Centre of Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247667, India
| | - Viney Kumar
- Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247667, India
| | - Haimanti Mukherjee
- Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247667, India
| | - Debrupa Lahiri
- Biomaterials and Multiscale Mechanics Laboratory, Department of Metallurgical and Materials Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247667, India
- Centre of Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247667, India
| | - Partha Roy
- Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247667, India
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Roychowdhury D, Gupta S, Qin X, Arighi CN, Vijay-Shanker K. emiRIT: a text-mining-based resource for microRNA information. DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION 2021; 2021:6287648. [PMID: 34048547 PMCID: PMC8163238 DOI: 10.1093/database/baab031] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 03/15/2021] [Accepted: 05/04/2021] [Indexed: 01/18/2023]
Abstract
microRNAs (miRNAs) are essential gene regulators, and their dysregulation often leads to diseases. Easy access to miRNA information is crucial for interpreting generated experimental data, connecting facts across publications and developing new hypotheses built on previous knowledge. Here, we present extracting miRNA Information from Text (emiRIT), a text-miningbased resource, which presents miRNA information mined from the literature through a user-friendly interface. We collected 149 ,233 miRNA –PubMed ID pairs from Medline between January 1997 and May 2020. emiRIT currently contains ‘miRNA –gene regulation’ (69 ,152 relations), ‘miRNA disease (cancer)’ (12 ,300 relations), ‘miRNA –biological process and pathways’ (23, 390 relations) and circulatory ‘miRNAs in extracellular locations’ (3782 relations). Biological entities and their relation to miRNAs were extracted from Medline abstracts using publicly available and in-house developed text-mining tools, and the entities were normalized to facilitate querying and integration. We built a database and an interface to store and access the integrated data, respectively. We provide an up-to-date and user-friendly resource to facilitate access to comprehensive miRNA information from the literature on a large scale, enabling users to navigate through different roles of miRNA and examine them in a context specific to their information needs. To assess our resource’s information coverage, we have conducted two case studies focusing on the target and differential expression information of miRNAs in the context of cancer and a third case study to assess the usage of emiRIT in the curation of miRNA information. Database URL: https://research.bioinformatics.udel.edu/emirit/
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Affiliation(s)
- Debarati Roychowdhury
- Department of Computer and Information Sciences, University of Delaware, 101 Smith Hall, 18 Amstel Ave, Newark, DE 19716, USA
| | - Samir Gupta
- Department of Computer and Information Sciences, University of Delaware, 101 Smith Hall, 18 Amstel Ave, Newark, DE 19716, USA
| | - Xihan Qin
- Department of Computer and Information Sciences, Center of Bioinformatics and Computational Biology, University of Delaware, 15 Innovation Way, Room 205, Newark, DE 19711, USA
| | - Cecilia N Arighi
- Department of Computer and Information Sciences, Center of Bioinformatics and Computational Biology, University of Delaware, 15 Innovation Way, Room 205, Newark, DE 19711, USA
| | - K Vijay-Shanker
- Department of Computer and Information Sciences, University of Delaware, 101 Smith Hall, 18 Amstel Ave, Newark, DE 19716, USA
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Ju C, Wang M, Tak E, Kim B, Emontzpohl C, Yang Y, Yuan X, Kutay H, Liang Y, Hall DR, Dar WA, Bynon JS, Carmeliet P, Ghoshal K, Eltzschig HK. Hypoxia-inducible factor-1α-dependent induction of miR122 enhances hepatic ischemia tolerance. J Clin Invest 2021; 131:140300. [PMID: 33792566 PMCID: PMC8011886 DOI: 10.1172/jci140300] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 02/10/2021] [Indexed: 12/29/2022] Open
Abstract
Hepatic ischemia and reperfusion (IR) injury contributes to the morbidity and mortality associated with liver transplantation. microRNAs (miRNAs) constitute a family of noncoding RNAs that regulate gene expression at the posttranslational level through the repression of specific target genes. Here, we hypothesized that miRNAs could be targeted to enhance hepatic ischemia tolerance. A miRNA screen in a murine model of hepatic IR injury pointed us toward the liver-specific miRNA miR122. Subsequent studies in mice with hepatocyte-specific deletion of miR122 (miR122loxP/loxP Alb-Cre+ mice) during hepatic ischemia and reperfusion revealed exacerbated liver injury. Transcriptional studies implicated hypoxia-inducible factor-1α (HIF1α) in the induction of miR122 and identified the oxygen-sensing prolyl hydroxylase domain 1 (PHD1) as a miR122 target. Further studies indicated that HIF1α-dependent induction of miR122 participated in a feed-forward pathway for liver protection via the enhancement of hepatic HIF responses through PHD1 repression. Moreover, pharmacologic studies utilizing nanoparticle-mediated miR122 overexpression demonstrated attenuated liver injury. Finally, proof-of-principle studies in patients undergoing orthotopic liver transplantation showed elevated miR122 levels in conjunction with the repression of PHD1 in post-ischemic liver biopsies. Taken together, the present findings provide molecular insight into the functional role of miR122 in enhancing hepatic ischemia tolerance and suggest the potential utility of pharmacologic interventions targeting miR122 to dampen hepatic injury during liver transplantation.
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Affiliation(s)
- Cynthia Ju
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
| | - Meng Wang
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
| | - Eunyoung Tak
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Boyun Kim
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
| | - Christoph Emontzpohl
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
| | - Yang Yang
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
| | - Xiaoyi Yuan
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
| | - Huban Kutay
- Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
| | - Yafen Liang
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
| | - David R. Hall
- Department of Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Wasim A. Dar
- Department of Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - J. Steve Bynon
- Department of Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Peter Carmeliet
- Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, and
- Center for Cancer Biology, Department of Oncology, Katholieke University Leuven, Leuven, Belgium
| | - Kalpana Ghoshal
- Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
- Department of Pathology, The Ohio State University, Columbus, Ohio, USA
| | - Holger K. Eltzschig
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
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MicroRNA Interference in Hepatic Host-Pathogen Interactions. Int J Mol Sci 2021; 22:ijms22073554. [PMID: 33808062 PMCID: PMC8036276 DOI: 10.3390/ijms22073554] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 03/24/2021] [Accepted: 03/27/2021] [Indexed: 12/14/2022] Open
Abstract
The liver is well recognized as a non-immunological visceral organ that is involved in various metabolic activities, nutrient storage, and detoxification. Recently, many studies have demonstrated that resident immune cells in the liver drive various immunological reactions by means of several molecular modulators. Understanding the mechanistic details of interactions between hepatic host immune cells, including Kupffer cells and lymphocytes, and various hepatic pathogens, especially viruses, bacteria, and parasites, is necessary. MicroRNAs (miRNAs), over 2600 of which have been discovered, are small, endogenous, interfering, noncoding RNAs that are predicted to regulate more than 15,000 genes by degrading specific messenger RNAs. Several recent studies have demonstrated that some miRNAs are associated with the immune response to pathogens in the liver. However, the details of the underlying mechanisms of miRNA interference in hepatic host-pathogen interactions still remain elusive. In this review, we summarize the relationship between the immunological interactions of various pathogens and hepatic resident immune cells, as well as the role of miRNAs in the maintenance of liver immunity against pathogens.
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Ngo MHT, Jeng HY, Kuo YC, Nanda JD, Brahmadhi A, Ling TY, Chang TS, Huang YH. The Role of IGF/IGF-1R Signaling in Hepatocellular Carcinomas: Stemness-Related Properties and Drug Resistance. Int J Mol Sci 2021; 22:ijms22041931. [PMID: 33669204 PMCID: PMC7919800 DOI: 10.3390/ijms22041931] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 02/10/2021] [Accepted: 02/10/2021] [Indexed: 12/12/2022] Open
Abstract
Insulin-like Growth Factor (IGF)/IGF-1 Receptor (IGF-1R) signaling is known to regulate stem cell pluripotency and differentiation to trigger cell proliferation, organ development, and tissue regeneration during embryonic development. Unbalanced IGF/IGF-1R signaling can promote cancer cell proliferation and activate cancer reprogramming in tumor tissues, especially in the liver. Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, with a high incidence and mortality rate in Asia. Most patients with advanced HCC develop tyrosine kinase inhibitor (TKI)-refractoriness after receiving TKI treatment. Dysregulation of IGF/IGF-1R signaling in HCC may activate expression of cancer stemness that leads to TKI refractoriness and tumor recurrence. In this review, we summarize the evidence for dysregulated IGF/IGF-1R signaling especially in hepatitis B virus (HBV)-associated HCC. The regulation of cancer stemness expression and drug resistance will be highlighted. Current clinical treatments and potential therapies targeting IGF/IGF-1R signaling for the treatment of HCC will be discussed.
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Affiliation(s)
- Mai-Huong Thi Ngo
- International PhD Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; (M.-H.T.N.); (J.D.N.); (A.B.)
- Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Han-Yin Jeng
- Research Center of Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei 11031, Taiwan; (H.-Y.J.); (Y.-C.K.)
| | - Yung-Che Kuo
- Research Center of Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei 11031, Taiwan; (H.-Y.J.); (Y.-C.K.)
| | - Josephine Diony Nanda
- International PhD Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; (M.-H.T.N.); (J.D.N.); (A.B.)
| | - Ageng Brahmadhi
- International PhD Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; (M.-H.T.N.); (J.D.N.); (A.B.)
| | - Thai-Yen Ling
- Department and Graduate Institute of Pharmacology, National Taiwan University, Taipei 11031, Taiwan
- Correspondence: (T.-Y.L.); (T.-S.C.); (Y.-H.H.); Tel.: +886-2-2312-3456 (ext. 8-8322) (T.-Y.L.); +886-5-3621-000 (ext. 2242) (T.-S.C.); +886-2-2736-1661 (ext. 3150) (Y.-H.H.)
| | - Te-Sheng Chang
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33382, Taiwan
- Division of Internal Medicine, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan
- Correspondence: (T.-Y.L.); (T.-S.C.); (Y.-H.H.); Tel.: +886-2-2312-3456 (ext. 8-8322) (T.-Y.L.); +886-5-3621-000 (ext. 2242) (T.-S.C.); +886-2-2736-1661 (ext. 3150) (Y.-H.H.)
| | - Yen-Hua Huang
- International PhD Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; (M.-H.T.N.); (J.D.N.); (A.B.)
- Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Research Center of Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei 11031, Taiwan; (H.-Y.J.); (Y.-C.K.)
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Center for Reproductive Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan
- Comprehensive Cancer Center, Taipei Medical University, Taipei 11031, Taiwan
- Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan
- PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
- Correspondence: (T.-Y.L.); (T.-S.C.); (Y.-H.H.); Tel.: +886-2-2312-3456 (ext. 8-8322) (T.-Y.L.); +886-5-3621-000 (ext. 2242) (T.-S.C.); +886-2-2736-1661 (ext. 3150) (Y.-H.H.)
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Tian Y, Zhong L, Gao S, Yu Y, Sun D, Liu X, Ji J, Yao Y, Liu Y, Jiang Z. LncRNA LINC00974 Downregulates miR-122 to Upregulate RhoA in Oral Squamous Cell Carcinoma. Cancer Biother Radiopharm 2021; 36:18-22. [PMID: 31702382 DOI: 10.1089/cbr.2019.2907] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Affiliation(s)
- Yanyan Tian
- Department of Stomatology, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China
| | - Lin Zhong
- Department of Stomatology, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China
| | - Shanling Gao
- Department of Stomatology, Baotou Eighth Hospital, Baotou, China
| | - Yunzhi Yu
- Department of Stomatology, Hospital of FIRMACO, The Fourth Affiliated of Inner Mongolia Medical University, Baotou, China
| | | | - Xiaxia Liu
- Department of Stomatology, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China
| | - Junying Ji
- Department of Stomatology, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China
| | - Yanan Yao
- Department of Stomatology, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China
| | - Yuexin Liu
- Department of Stomatology, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China
| | - Zhiwei Jiang
- Department of Stomatology, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China
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