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Umezu T, Tanaka S, Kubo S, Enomoto M, Tamori A, Ochiya T, Taguchi Y, Kuroda M, Murakami Y. Characterization of circulating miRNAs in the treatment of primary liver tumors. Cancer Rep (Hoboken) 2024; 7:e1964. [PMID: 38146079 PMCID: PMC10849994 DOI: 10.1002/cnr2.1964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 11/13/2023] [Accepted: 12/06/2023] [Indexed: 12/27/2023] Open
Abstract
BACKGROUND AND AIM Circulating micro RNAs (miRNAs) indicate clinical pathologies such as inflammation and carcinogenesis. In this study, we aimed to investigate whether miRNA expression level patterns in could be used to diagnose hepatocellular carcinoma (HCC) and biliary tract cancer (BTC), and the relationship miRNA expression patterns and cancer etiology. METHODS Patients with HCC and BTC with indications for surgery were selected for the study. Total RNA was extracted from the extracellular vesicle (EV)-rich fraction of the serum and analyzed using Toray miRNA microarray. Samples were divided into two cohorts in order of collection, the first 85 HCC were analyzed using a microarray based on miRBase ver.2.0 (hereafter v20 cohort), and the second 177 HCC and 43 BTC were analyzed using a microarray based on miRBase ver.21 (hereafter v21 cohort). RESULTS Using miRNA expression patterns, we found that HCC and BTC could be identified with an area under curve (AUC) 0.754 (v21 cohort). Patients with anti-hepatitis C virus (HCV) treatment (SVR-HCC) and without antiviral treatment (HCV-HCC) could be distinguished by an AUC 0.811 (v20 cohort) and AUC 0.798 (v21 cohort), respectively. CONCLUSIONS In this study, we could diagnose primary hepatic malignant tumor using miRNA expression patterns. Moreover, the difference of miRNA expression in SVR-HCC and HCV-HCC can be important information for enclosing cases that are prone to carcinogenesis after being cured with antiviral agents, but also for uncovering the mechanism for some carcinogenic potential remains even after persistent virus infection has disappeared.
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Affiliation(s)
- Tomohiro Umezu
- Department of Molecular PathologyTokyo Medical UniversityTokyoJapan
| | - Shogo Tanaka
- Department of Hepato‐Biliary‐Pancreatic SurgeryOsaka Metropolitan University, Graduate School of MedicineOsakaJapan
| | - Shoji Kubo
- Department of Hepato‐Biliary‐Pancreatic SurgeryOsaka Metropolitan University, Graduate School of MedicineOsakaJapan
| | - Masaru Enomoto
- Department of Hepatology, Graduate School of MedicineOsaka Metropolitan University, Graduate School of MedicineOsakaJapan
| | - Akihiro Tamori
- Department of Hepatology, Graduate School of MedicineOsaka Metropolitan University, Graduate School of MedicineOsakaJapan
| | - Takahiro Ochiya
- Department of Molecular and Cellular Medicine, Institute of Medical ScienceTokyo Medical UniversityTokyoJapan
| | | | - Masahiko Kuroda
- Department of Molecular PathologyTokyo Medical UniversityTokyoJapan
| | - Yoshiki Murakami
- Department of Molecular PathologyTokyo Medical UniversityTokyoJapan
- Department of DentistryAsahi UniversityGifuJapan
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Hasheminasabgorji E, Mishan MA, Tabari MAK, Bagheri A. miR-638: A Promising Cancer Biomarker with Therapeutic Potential. Curr Mol Med 2023; 23:377-389. [PMID: 35382724 DOI: 10.2174/1566524022666220405125900] [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: 10/26/2021] [Revised: 02/03/2022] [Accepted: 02/16/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND There is an unmet need to improve the diagnosis of cancer with precise treatment strategies. Therefore, more powerful diagnostic, prognostic, and therapeutic biomarkers are needed to overcome tumor cells. microRNAs (miRNAs, miRs), as a class of small non-coding RNAs, play essential roles in cancer through the tumor-suppressive or oncogenic effects by post-transcriptional regulation of their targets. Many studies have provided shreds of evidence on aberrantly expressed miRNAs in numerous cancers and have shown that miRNAs could play potential roles as diagnostic, prognostic, and even therapeutic biomarkers in patients with cancers. Findings have revealed that miR-638 over or underexpression might play a critical role in cancer initiation, development, and progression. However, the mechanistic effects of miR-638 on cancer cells are still controversial. CONCLUSION In the present review, we have focused on the diagnostic, prognostic, and therapeutic potentials of miR-638 and discussed its mechanistic roles in various types of cancers.
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Affiliation(s)
- Elham Hasheminasabgorji
- Department of Clinical Biochemistry and Medical Genetics, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
- Arnie Charbonneau Cancer Institute, Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Mohammad Amir Mishan
- Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Amin Khazeei Tabari
- Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
- USERN Office, Mazandaran University of Medical Sciences, Sari, Iran
| | - Abouzar Bagheri
- Department of Clinical Biochemistry and Medical Genetics, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
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Badami E, Busà R, Douradinha B, Russelli G, Miceli V, Gallo A, Zito G, Conaldi PG, Iannolo G. Hepatocellular carcinoma, hepatitis C virus infection and miRNA involvement: Perspectives for new therapeutic approaches. World J Gastroenterol 2022; 28:2417-2428. [PMID: 35979260 PMCID: PMC9258280 DOI: 10.3748/wjg.v28.i22.2417] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/22/2022] [Accepted: 04/15/2022] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is the principal etiology of cirrhosis and, ultimately, hepatocellular carcinoma (HCC). At present, approximately 71 million people are chronically infected with HCV, and 10%-20% of these are expected to develop severe liver complications throughout their lifetime. Scientific evidence has clearly shown the causal association between miRNAs, HCV infection and HCC. Although it is not completely clear whether miRNA dysregulation in HCC is the cause or the consequence of its development, variations in miRNA patterns have been described in different liver diseases, including HCC. Many studies have analyzed the importance of circulating miRNAs and their effect on cell proliferation and apoptosis. In this Review, we aim to summarize current knowledge on the association between miRNA, HCV and HCC from a diagnostic point of view, and also the potential implications for therapeutic approaches.
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Affiliation(s)
- Ester Badami
- Regenerative Medicine and Immunotherapy Area, Fondazione Ri.MED, Palermo 90127, Italy
| | - Rosalia Busà
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Bruno Douradinha
- Regenerative Medicine and Immunotherapy Area, Fondazione Ri.MED, Palermo 90127, Italy
| | - Giovanna Russelli
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Vitale Miceli
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Alessia Gallo
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Giovanni Zito
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Pier Giulio Conaldi
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Gioacchin Iannolo
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
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Mawatari S, Kumagai K, Oda K, Tabu K, Ijuin S, Fujisaki K, Tashima S, Inada Y, Uto H, Saisyoji A, Hiramine Y, Hashiguchi M, Tamai T, Hori T, Taniyama O, Toyodome A, Sakae H, Kure T, Sakurai K, Moriuchi A, Kanmura S, Ido A. Features of patients who developed hepatocellular carcinoma after direct-acting antiviral treatment for hepatitis C Virus. PLoS One 2022; 17:e0262267. [PMID: 35020772 PMCID: PMC8754290 DOI: 10.1371/journal.pone.0262267] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 12/21/2021] [Indexed: 02/07/2023] Open
Abstract
Background The features of hepatitis C virus patients with a sustained virologic response (SVR) who developed hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) therapy are unclear. Methods The study population included 1494 DAA-SVR patients without a history of HCC. The cumulative carcinogenesis rate after the end of treatment (EOT) and factors related to HCC were analyzed. Results Sixty (4.0%) patients developed HCC during a median observation period of 47.6 months. At four years, the cumulative carcinogenesis rate was 4.7%. A Cox proportional hazards analysis showed that age ≥73 years (hazard ratio [HR]: 2.148), male sex (HR: 3.060), hyaluronic acid (HA) ≥75 ng/mL (HR: 3.996), alpha-fetoprotein at EOT (EOT-AFP) ≥5.3 ng/mL (HR: 4.773), and albumin at EOT (EOT-Alb) <3.9 g/dL (HR: 2.305) were associated with HCC development. Especially, EOT-AFP ≥5.3 ng/mL was associated with HCC development after 3 years from EOT (HR: 6.237). Among patients who developed HCC, AFP did not increase in patients with EOT-AFP <5.3 ng/mL at the onset of HCC. Of these 5 factors, EOT-AFP ≥5.3 ng/mL was scored as 2 points; the others were scored as 1 point. The 4-year cumulative carcinogenesis rate for patients with total scores of 0–2, 3–4, and 5–6 points were 0.6%, 11.9%, and 27.1%, respectively (p<0.001). Conclusions EOT-AFP ≥5.3 ng/mL is useful for predicting HCC development after an SVR. However, AFP does not increase in patients with EOT-AFP <5.3 ng/mL at the onset of HCC. The combination of EOT-AFP, age, sex, HA, and EOT-Alb is important for predicting carcinogenesis.
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Affiliation(s)
- Seiichi Mawatari
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- * E-mail:
| | - Kotaro Kumagai
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kohei Oda
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kazuaki Tabu
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Sho Ijuin
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kunio Fujisaki
- Department of Hepatology, Kirishima Medical Center, Hayato-cho, Kirishima, Kagoshima, Japan
| | - Shuzo Tashima
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Department of Hepatology, Kirishima Medical Center, Hayato-cho, Kirishima, Kagoshima, Japan
| | - Yukiko Inada
- Center for Digestive and Liver Diseases, Miyazaki Medical Center Hospital, Miyazaki, Japan
| | - Hirofumi Uto
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Center for Digestive and Liver Diseases, Miyazaki Medical Center Hospital, Miyazaki, Japan
| | - Akiko Saisyoji
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Department of Internal Medicine, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Yasunari Hiramine
- Department of Internal Medicine, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Masafumi Hashiguchi
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Department of Gastroenterology and Hepatology, Kagoshima City Hospital, Kagoshima, Japan
| | - Tsutomu Tamai
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Department of Gastroenterology and Hepatology, Kagoshima City Hospital, Kagoshima, Japan
| | - Takeshi Hori
- Department of Gastroenterology and Hepatology, Kagoshima City Hospital, Kagoshima, Japan
| | - Ohki Taniyama
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Ai Toyodome
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Haruka Sakae
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Takeshi Kure
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Department of Gastroenterology, Kagoshima Medical Association Hospital, Kagoshima, Japan
| | - Kazuhiro Sakurai
- Department of Gastroenterology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan
| | - Akihiro Moriuchi
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Department of Gastroenterology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan
| | - Shuji Kanmura
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Akio Ido
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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In Hepatocellular Carcinoma, miRNA-296-3p Targets MSL2 and Suppresses Cell Proliferation and Invasion. JOURNAL OF ONCOLOGY 2021; 2021:7430468. [PMID: 34899909 PMCID: PMC8660223 DOI: 10.1155/2021/7430468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 11/11/2021] [Accepted: 11/13/2021] [Indexed: 11/17/2022]
Abstract
Hepatocellular carcinoma (HCC) is the third-highest cause of cancer-related death in the world. miRNAs have a role in cell division, differentiation, and death biological processes. They are typically dysregulated in cancers, affecting tumor progression. miRNA-296-3p appears to play a crucial role in cancer control, according to new research. However, its expression and roles in HCC are unknown. This study used qRT-PCR and western blotting to detect the miRNA-296-3p and male-specific lethal 2 (MSL2) expression. In addition, cell proliferation, migration, invasion, and apoptosis were studied using CCK-8, flow cytometric analysis, colony formation assay, wound healing test, and transwell assays. The results show that miRNA-296-3p is underexpressed in HCC cell lines, particularly in Huh-7 and HepG2 cells. miRNA-296-3p overexpression lowers the ability of HCC cells to proliferate, migrate, and invade while increasing cell death. Luciferase reporter experiments revealed that the MSL2 is a direct target of miRNA-296-3p. Furthermore, overexpression of miRNA-296-3p reduced MSL2 mRNA and protein levels considerably, according to our findings. Furthermore, the rescue experiments showed that the MSL2 overexpression partially blocked the inhibition effects of miRNA-296-3p mimic on the proliferation and migration of HCC cells. The above results show that miRNA-296-3p may have a repressive effect in HCC by targeting MSL2 and could be used as a therapeutic target for HCC treatment.
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Hsa-miR-330-5p Aggravates Thyroid Carcinoma via Targeting FOXE1. JOURNAL OF ONCOLOGY 2021; 2021:1070365. [PMID: 34306074 PMCID: PMC8272668 DOI: 10.1155/2021/1070365] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 06/18/2021] [Indexed: 11/23/2022]
Abstract
Background Thyroid carcinoma (TC) is one of the frequent endocrine malignancies, and growing evidence suggests that aberrant microRNA (miRNA) expression contributes to TC development and progression. Nevertheless, the function of miR-330-5p in the progression of TC remains unknown. Methods The expression levels of miR-330-5 in patients with thyroid carcinoma and healthy controls were detected, and their potential diagnostic and prognostic values were analyzed. Results In this study, we firstly found that miR-330-5p expression was markedly upregulated in TC tissue and cell lines. Functionally, the downregulation of miR-330-5p suppressed TC cell proliferation, migration, and invasion. Further studies revealed that miR-330-5p negatively regulated the expression of forkhead box E1 (FOXE1). More importantly, the results of rescue experiments suggested that FOXE1 overexpression reduced the positive effects of miR-330-5p overexpression in TPC-1 and K-1 cells. Conclusions This work revealed that miR-330-5p facilitated the TC progression through targeting FOXE1, which may offer novel therapeutic options for TC.
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The Relevance of MicroRNAs in the Pathogenesis and Prognosis of HCV-Disease: The Emergent Role of miR-17-92 in Cryoglobulinemic Vasculitis. Viruses 2020; 12:v12121364. [PMID: 33260407 PMCID: PMC7761224 DOI: 10.3390/v12121364] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 11/18/2020] [Accepted: 11/27/2020] [Indexed: 12/26/2022] Open
Abstract
Hepatitis C virus (HCV) is a major public health problem. HCV is a hepatotropic and lymphotropic virus that leads to hepatocellular carcinoma (HCC) and lymphoproliferative disorders such as cryoglobulinemic vasculitis (CV) and non-Hodgkin's lymphoma (NHL). The molecular mechanisms by which HCV induces these diseases are not fully understood. MicroRNAs (miRNAs) are small non-coding molecules that negatively regulate post-transcriptional gene expression by decreasing their target gene expression. We will attempt to summarize the current knowledge on the role of miRNAs in the HCV life cycle, HCV-related HCC, and lymphoproliferative disorders, focusing on both the functional effects of their deregulation as well as on their putative role as biomarkers, based on association analyses. We will also provide original new data regarding the miR 17-92 cluster in chronically infected HCV patients with and without lymphoproliferative disorders who underwent antiviral therapy. All of the cluster members were significantly upregulated in CV patients compared to patients without CV and significantly decreased in those who achieved vasculitis clinical remission after viral eradication. To conclude, miRNAs play an important role in HCV infection and related oncogenic processes, but their molecular pathways are not completely clear. In some cases, they may be potential therapeutic targets or non-invasive biomarkers of tumor progression.
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miR-665 promotes hepatocellular carcinoma cell migration, invasion, and proliferation by decreasing Hippo signaling through targeting PTPRB. Cell Death Dis 2018; 9:954. [PMID: 30237408 PMCID: PMC6148030 DOI: 10.1038/s41419-018-0978-y] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Revised: 08/20/2018] [Accepted: 08/23/2018] [Indexed: 12/20/2022]
Abstract
Growing evidence suggests that aberrant microRNA (miRNA) expression contributes to hepatocellular carcinoma (HCC) development and progression. However, the potential role and mechanism of miR-665 in the progression of liver cancer remains largely unknown. Our current study showed that miR-665 expression was upregulated in HCC cells and tissues. High expression of miR-665 exhibited more severe tumor size, vascular invasion and Edmondson grading in HCC patients. Gain- or loss-of-function assays demonstrated that miR-665 promoted cell proliferation, migration, invasion, and the epithelial-mesenchymal transition (EMT) of HCC cells in vitro and in vivo. Tyrosine phosphatase receptor type B (PTPRB) was downregulated in HCC tissues, and was negatively correlated with miR-665 expression. Through western blotting and luciferase reporter assay, PTPRB was identified as a direct downstream target of miR-665. Restoration of PTPRB reverses the effects of miR-665 on HCC migration, invasion, and cell proliferation. A mechanistic study showed that PTPTRB mediated the functional role of miR-665 through regulation of the Hippo signaling pathway. In conclusion, our results suggested that miR-665 was a negative regulator of the PTPRB and could promote tumor proliferation and metastasis in HCC through decreasing Hippo signaling pathway activity, which can be a potential target for HCC treatment.
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Principal Component Analysis-Based Unsupervised Feature Extraction Applied to Single-Cell Gene Expression Analysis. ACTA ACUST UNITED AC 2018. [DOI: 10.1007/978-3-319-95933-7_90] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Wada T, Toma T, Matsuda Y, Yachie A, Itami S, Taguchi YH, Murakami Y. Microarray analysis of circulating microRNAs in familial Mediterranean fever. Mod Rheumatol 2017; 27:1040-1046. [PMID: 28165838 DOI: 10.1080/14397595.2017.1285845] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Accepted: 01/09/2017] [Indexed: 10/25/2022]
Abstract
OBJECTIVES Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in MEFV. Mutations in exon 10 are associated with typical FMF phenotypes, whereas the pathogenic role of variants in exons 2 and 3 remains uncertain. Recent evidence suggests that circulating microRNAs (miRNAs) are potentially useful biomarkers in several diseases. Therefore, their expression was assessed in FMF. METHODS The subjects were 24 patients with FMF who were between attacks: eight with exon 10 mutations (group A), eight with exon 3 mutations (group B), and eight without exon 3 or 10 mutations (group C). We also investigated eight cases of PFAPA as disease controls. Exosome-rich fractionated RNA was subjected to miRNA profiling by microarray. RESULTS Using the expression patterns of 26 miRNAs, we classified FMF (groups A, B, and C) and PFAPA with 78.1% accuracy. In FMF patients, groups A and B, A and C, and B and C were distinguished with 93.8, 87.5, and 100% accuracy using 24, 30, and 25 miRNA expression patterns, respectively. CONCLUSIONS These findings suggest that expression patterns of circulating miRNAs differ among FMF subgroups based on MEFV mutations between FMF episodes. These patterns may serve as a useful biomarker for detecting subgroups of FMF.
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Affiliation(s)
- Taizo Wada
- a Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences , Kanazawa University , Kanazawa , Japan
| | - Tomoko Toma
- a Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences , Kanazawa University , Kanazawa , Japan
| | - Yusuke Matsuda
- a Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences , Kanazawa University , Kanazawa , Japan
| | - Akihiro Yachie
- a Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences , Kanazawa University , Kanazawa , Japan
| | - Saori Itami
- b Department of Hepatology, Graduate School of Medicine , Osaka City University , Osaka , Japan
| | - Y-H Taguchi
- c Department of Physics , Chuo University , Tokyo , Japan
| | - Yoshiki Murakami
- b Department of Hepatology, Graduate School of Medicine , Osaka City University , Osaka , Japan
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Cheng L, Wang H, Han S. MiR-3910 Promotes the Growth and Migration of Cancer Cells in the Progression of Hepatocellular Carcinoma. Dig Dis Sci 2017; 62:2812-2820. [PMID: 28823082 DOI: 10.1007/s10620-017-4670-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2017] [Accepted: 06/30/2017] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Previous studies have reported that specific depletion of mammalian sterile-like kinase (MST1) in the mouse liver driven Hepatocellular carcinoma (HCC). However, how the expression of MST1 was regulated in the progression of HCC remains largely unknown. MATERIALS AND METHODS The expression of miR-3910 in the HCC tissues and cell lines were examined using q-PCR. The functions of miR-3910 in HCC were examined using MTT assay, Boyden chamber assay and soft agar assay. The effects of miR-3910 on the metastasis of HCC cells were evaluated using the mouse model. RESULTS Here, we have shown that miR-3910 regulated the expression of MST1. MiR-3910 was up-regulated in HCC samples and cell lines, and the expression of miR-3910 was induced by the oncogenic RasV12. In the functional study, miR-3910 was found to promote the growth and migration of HCC cells, and knocking down miR-3910 inhibited the metastasis of HCC cells. Mechanically, it was found that miR-3910 activated YAP signaling by targeting MST1. CONCLUSION Taken together, this study demonstrated that miR-3910 exerted oncogenic effects on the progression of HCC and suggested that miR-3910 might be a therapeutic target for cancer therapy.
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Affiliation(s)
- Lina Cheng
- Department of Gastroenterology, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), 7th Weiwu Road, Zhengzhou, 450003, Henan Province, China
| | - Hongwei Wang
- Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Shuangyin Han
- Department of Gastroenterology, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), 7th Weiwu Road, Zhengzhou, 450003, Henan Province, China.
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12
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Li Y, Turpin CP, Wang S. Role of thrombospondin 1 in liver diseases. Hepatol Res 2017; 47:186-193. [PMID: 27492250 PMCID: PMC5292098 DOI: 10.1111/hepr.12787] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Revised: 07/13/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023]
Abstract
Thrombospondin 1 (TSP1) is a matricellular glycoprotein that can be secreted by many cell types. Through binding to extracellular proteins and/or cell surface receptors, TSP1 modulates a variety of cellular functions. Since its discovery in 1971, TSP1 has been found to play important roles in multiple biological processes including angiogenesis, apoptosis, latent transforming growth factor-β activation, and immune regulation. Thrombospondin 1 is also involved in regulating many organ functions. However, the role of TSP1 in liver diseases has not been extensively addressed. In this review, we summarize the findings about the possible role that TSP1 plays in chronic liver diseases focusing on non-alcoholic fatty liver diseases, liver fibrosis, and hepatocellular carcinoma.
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Affiliation(s)
- Yanzhang Li
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA
- Medical College of Henan University, Kaifeng, Henan 475004, China
| | - Courtney P Turpin
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA
| | - Shuxia Wang
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA
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