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Liu Y, Zhang K, Yang X. CircMCTP2 enhances the progression of bladder cancer by regulating the miR-99a-5p/FZD8 axis. J Egypt Natl Canc Inst 2024; 36:8. [PMID: 38494582 DOI: 10.1186/s43046-024-00206-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 01/13/2024] [Indexed: 03/19/2024] Open
Abstract
BACKGROUND CircRNAs and miRNAs are involved in the progression of tumor. CircMCTP2 is considered as a novel tumor promoter. However, the exact functions of circMCTP2 in bladder cancer are still unclear. This study was designed to explore the underlying mechanisms of circMCTP2-modulated tumor development in bladder cancer. METHODS The present study is an original research. The levels of circMCTP2 in a total of 39 bladder cancer specimens and cell lines were determined by RT-qPCR. The expression of FZD8 in T24 and RT-4 cells treated with miR-99a-5p mimics were examined using western blotting. In addition, the proliferative, migrative and invasive abilities of transfected cells were determined by CCK8 and Transwell assays. Furthermore, the apoptosis of transfected cells was evaluated using flow cytometry. Dual luciferase reporter assay was performed to elucidate the relationship between miR-99a-5p and circMCTP2/FZD8. RESULTS The levels of circMCTP2 were elevated in bladder cancer samples and cells, and this was related to worse survival rate. Downregulation of circMCTP2 suppressed growth and metastasis of cells, whereas the apoptotic rate of cells was enhanced. The levels of miR-99a-5rp was elevated after the downregulation of circMCTP2. Moreover, reverse correlation between the expression of miR-99a-5p and circMCTP2 was revealed in bladder cancer specimens. Additionally, FZD8 was the putative target of miR-99a-5p and the mimics of miR-99a-5p inhibited the proliferation, migration and invasion of bladder cancer cells via the FZD8/Wnt-b-catenin axis. Moreover, circMCTP2 regulated the growth and metastasis of bladder cancer cells potentially through regulating the miR-99a-5p/FZD8/Wnt-b-catenin axis. In summary, circMCTP2 was considered as an oncogenic factor through regulating the miR-99a-5p/FZD8/Wnt-b-catenin axis. CONCLUSIONS This novel signaling could regulate the biological behaviours of bladder cancer cells, and these findings highlighted circMCTP2 as a critical target for treating bladder cancer.
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Affiliation(s)
- Yan Liu
- Department of Urinary Surgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, 121000, China.
| | - Kexin Zhang
- Department of Urinary Surgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, 121000, China
| | - Xianxu Yang
- Department of Urinary Surgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, 121000, China
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Kang MK, Kim G, Park JG, Jang SY, Lee HW, Tak WY, Kweon YO, Park SY, Lee YR, Hur K. Tissue Circular RNA_0004018 and 0003570 as Novel Prognostic Biomarkers for Hepatitis B-Related Hepatocellular Carcinoma. Genes (Basel) 2023; 14:1963. [PMID: 37895312 PMCID: PMC10606672 DOI: 10.3390/genes14101963] [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: 09/24/2023] [Revised: 10/13/2023] [Accepted: 10/19/2023] [Indexed: 10/29/2023] Open
Abstract
The clinical significance of hsa_circ_0004018 and hsa_circ_0003570 in patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) is unclear. We aimed to explore the clinical significance and prognostic utility of these two circular RNAs (circRNAs) in patients with HBV-HCC. Based on 86 paired tissue samples of HCC and adjacent non-HCC, the relative expression profiles of hsa_circ_0004018 and hsa_circ_0003570 were determined using quantitative real-time polymerase chain reactions. The cut-off values were the median expression of each of the two circRNAs in 86 patients with HBV-HCC. The combination group comprised patients with high levels of the two circRNAs. Clinicopathological features, body composition profiles at the L3 level, and survival rates were investigated. The expression of hsa_circ_0004018 and hsa_circ_0003570 was downregulated in HCC tissues compared with non-HCC tissues. High expression levels of hsa_circ_0003570 (hazard ratio (HR), 0.437; p = 0.009) and hsa_circ_0004018 (HR, 0.435; p = 0.005) were inversely independent risk factors for overall and progression-free survival in patients with HBV-HCC, whereas the combination group was also an inversely independent risk factor for overall (HR, 0.399; p = 0.005) and progression-free survival (HR, 0.422; p = 0.003) in patients with HBV-HCC. The combination of hsa_circ_0003570 and hsa_circ_0004018 may be a potential prognostic biomarker for HBV-HCC.
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Affiliation(s)
- Min-Kyu Kang
- Department of Internal Medicine, College of Medicine, Yeungnam University, 170 Hyunchung-ro, Nam-gu, Daegu 42415, Republic of Korea
| | - Gyeonghwa Kim
- Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea
| | - Jung Gil Park
- Department of Internal Medicine, College of Medicine, Yeungnam University, 170 Hyunchung-ro, Nam-gu, Daegu 42415, Republic of Korea
| | - Se Young Jang
- Department of Internal Medicine, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Republic of Korea
| | - Hye Won Lee
- Department of Pathology, School of Medicine, Keimyung University, 1095 Dalgubeoldae-ro, Dalseo-gu, Daegu 41944, Republic of Korea
| | - Won Young Tak
- Department of Internal Medicine, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Republic of Korea
| | - Young Oh Kweon
- Department of Internal Medicine, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Republic of Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Republic of Korea
| | - Yu Rim Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Republic of Korea
| | - Keun Hur
- Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea
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Yepmo M, Potier JB, Pinget M, Grabarz A, Bouzakri K, Dumond Bourie A. Discussing the role of circular RNA in the pathogenesis of non-alcoholic fatty liver disease and its complications. Front Endocrinol (Lausanne) 2022; 13:1035159. [PMID: 36407314 PMCID: PMC9667057 DOI: 10.3389/fendo.2022.1035159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 10/17/2022] [Indexed: 01/24/2023] Open
Abstract
Circular RNAs (circRNAs) are class of non-coding RNA, which are characterized by a covalently closed loop structure. Functionally they can act on cellular physiology, notably by sponging microRNAs (miR), regulating gene expression or interacting with binding protein. To date, circRNAs might represent an interesting, underexploited avenue for new target discovery for therapeutic applications, especially in the liver. The first characteristic of non-alcoholic fatty liver disease (NAFLD) is hepatic cholesterol accumulation, followed by its advanced form of the affection, nonalcoholic steatohepatitis (NASH), due to the occurrence of lobular inflammation, irreversible fibrosis, and in some cases hepatocellular carcinoma (HCC). Therefore, studies have investigated the importance of the dysregulation of circRNAs in the onset of metabolic disorders. In this review, we summarize the potential role of circRNAs in the development of metabolic diseases associated with the liver such as NAFLD or NASH, and their potential to become therapeutic strategies for these pathologies.
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Affiliation(s)
- Melissa Yepmo
- Centre européen d’étude du Diabète, Unité Mixte de Recherche de l’Université de Strasbourg « Diabète et Thérapeutique », Strasbourg, France
| | - Jean-Baptiste Potier
- Centre européen d’étude du Diabète, Unité Mixte de Recherche de l’Université de Strasbourg « Diabète et Thérapeutique », Strasbourg, France
- ILONOV, Strasbourg, France
| | - Michel Pinget
- Centre européen d’étude du Diabète, Unité Mixte de Recherche de l’Université de Strasbourg « Diabète et Thérapeutique », Strasbourg, France
| | | | - Karim Bouzakri
- Centre européen d’étude du Diabète, Unité Mixte de Recherche de l’Université de Strasbourg « Diabète et Thérapeutique », Strasbourg, France
- ILONOV, Strasbourg, France
| | - Aurore Dumond Bourie
- Centre européen d’étude du Diabète, Unité Mixte de Recherche de l’Université de Strasbourg « Diabète et Thérapeutique », Strasbourg, France
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Circular Noncoding RNA hsa_circ_0003570 as a Prognostic Biomarker for Hepatocellular Carcinoma. Genes (Basel) 2022; 13:genes13081484. [PMID: 36011395 PMCID: PMC9407695 DOI: 10.3390/genes13081484] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 08/14/2022] [Accepted: 08/16/2022] [Indexed: 11/17/2022] Open
Abstract
Circular RNAs (circRNAs) are potential biomarkers owing to their stability, tissue specificity, and abundance. This study aimed to evaluate the clinical significance of hsa_circ_0003570 expression and to investigate its potential as a biomarker in hepatocellular carcinoma (HCC). We evaluated hsa_circ_0003570 expression in 121 HCC tissue samples, its association with clinicopathological characteristics, and overall and progression-free survival. Hsa_circ_0003570 expression was downregulated in HCC tissues. Low hsa_circ_0003570 expression was more common in tumors larger than 5 cm (odds ratio (OR), 6.369; 95% confidence interval (CI), 2.725−14.706; p < 0.001), vessel invasion (OR, 5.128; 95% CI, 2.288−11.494; p < 0.001); advanced tumor-node metastasis stage (III/IV; OR, 4.082; 95% CI, 1.866−8.929; p < 0.001); higher Barcelona Clinic Liver Cancer stage (B/C; OR, 3.215; 95% CI, 1.475−6.993; p = 0.003); and higher AFP (>200 ng/mL; OR, 2.475; 95% CI, 1.159−5.291; p = 0.018). High hsa_circ_0003570 expression was an independent prognostic factor for overall survival (hazard ratio (HR), 0.541; 95% confidence interval (CI), 0.327−0.894; p = 0.017) and progression-free survival (HR, 0.633; 95% CI, 0.402−0.997; p = 0.048). Hsa_circ_0003570 is a potential prognostic biomarker in patients with HCC, and further validation of hsa_circ_0003570 is needed.
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Niu ZS, Wang WH. Circular RNAs in hepatocellular carcinoma: Recent advances. World J Gastrointest Oncol 2022; 14:1067-1085. [PMID: 35949213 PMCID: PMC9244981 DOI: 10.4251/wjgo.v14.i6.1067] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 09/22/2021] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
Circular RNAs (circRNAs) have covalently closed loop structures at both ends, exhibiting characteristics dissimilar to those of linear RNAs. Emerging evidence suggests that aberrantly expressed circRNAs play crucial roles in hepatocellular carcinoma (HCC) by affecting the proliferation, apoptosis and invasive capacity of HCC cells. Certain circRNAs may be used as biomarkers to diagnose and predict the prognosis of HCC. Therefore, circRNAs are expected to become novel biomarkers and therapeutic targets for HCC. Herein, we briefly review the characteristics and biological functions of circRNAs, focusing on their roles in HCC to provide new insights for the early diagnosis and targeted therapy of HCC.
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Affiliation(s)
- Zhao-Shan Niu
- Laboratory of Micromorphology, School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Wen-Hong Wang
- Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong Province, China
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