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Liu S, Wu T, Song X, Quan L, Wang X, Liu Q, Zhou X. Single-cell sequencing reveals PTX3 involvement in ovarian cancer metastasis. J Ovarian Res 2024; 17:235. [PMID: 39580424 PMCID: PMC11585133 DOI: 10.1186/s13048-024-01558-2] [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: 02/15/2024] [Accepted: 11/13/2024] [Indexed: 11/25/2024] Open
Abstract
BACKGROUND Pentraxin 3 (PTX3) has been associated with the development and progression of various malignant tumors. However, its roles and the mechanisms underlying its involvement in ovarian cancer (OC) peritoneal metastasis remain unclear. METHODS Single-cell RNA sequencing (scRNA-seq) and immunohistochemistry (IHC) were conducted to determine the expression profiles, potential functionalities, and underlying mechanisms of PTX3 within the context of OC. To assess the proliferative response of OC cells, we utilized both EdU (5-ethynyl-2' -deoxyuridine) and CCK8 assays. The role of PTX3 in facilitating cell migration and invasion was quantified through the use of Transwell assays. The protein expression levels were meticulously analyzed via Western blotting. Furthermore, to explore the interactions between proteins, we conducted immunofluorescence (IF) staining and co-immunoprecipitation (Co-IP) experiments. To determine the factors responsible for the upregulation of PTX3, we performed both coculture and suspension assays, providing a comprehensive approach to understanding the regulatory mechanisms involved. RESULTS This study confirmed, for the first time, that the expression of PTX3 in OC metastatic lesions is greater than that in primary lesions and that tumor cells with high PTX3 expression have greater metastatic ability. PTX3 can activate the EMT and NF-κB signaling pathways in OC cells and can interact with the TLR4 and CD44 receptors in OC cells. Additionally, PTX3's modulation of the EMT and NF-κB pathways is partially dependent on its interaction with TLR4. Furthermore, this study revealed the intercellular regulatory network related to PTX3 in OC cells via bioinformatic analysis. High levels of PTX3 in OC cells potentially enhance the attraction of dendritic cells (DCs) and CD4 + T cells while diminishing the recruitment of B cells and CD8 + T cells. Finally, this study indicated that PTX3 upregulation was driven by multiple factors, including specific transcription factors (TFs) and modifications within the tumor microenvironment (TME). CONCLUSIONS Our research revealed the contribution of PTX3 to the peritoneal dissemination process in OC patients, identifying a novel potential biomarker and therapeutic target for this disease.
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Affiliation(s)
- Shuangyan Liu
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, China
| | - Tianhao Wu
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, China
| | - Xueying Song
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, China
| | - Linru Quan
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, China
| | - Xinyi Wang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, China
| | - Qing Liu
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, China.
| | - Xin Zhou
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, China.
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Tsai YH, Hong JJ, Cheng CM, Cheng MH, Chen CH, Hsieh ML, Hsieh KS, Shen CF. Case report: Cytokine and miRNA profiling in multisystem inflammatory syndrome in children. Front Med (Lausanne) 2024; 11:1422588. [PMID: 39149604 PMCID: PMC11324540 DOI: 10.3389/fmed.2024.1422588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 07/15/2024] [Indexed: 08/17/2024] Open
Abstract
Multisystem inflammatory syndrome in children (MIS-C) is an imperative pediatric inflammatory condition closely linked to COVID-19, which garners substantial attention since the onset of the pandemic. Like Kawasaki illness, this condition is characterized by an overactive immune response, leading to symptoms including pyrexia, cardiac and renal complications. To elucidate the pathogenesis of MIS-C and identify potential biomarkers, we conducted an extensive examination of specific cytokines (IL-6, IL-1β, IL-6R, IL-10, and TNF-α) and microRNA (miRNA) expression profiles at various intervals (ranging from 3 to 20 days) in the peripheral blood sample of a severely affected MIS-C patient. Our investigation revealed a gradual decline in circulating levels of IL-6, IL-1β, IL-10, and TNF-α following intravenous immune globulin (IVIG) therapy. Notably, IL-6 exhibited a significant reduction from 74.30 to 1.49 pg./mL, while IL-6R levels remained consistently stable throughout the disease course. Furthermore, we observed an inverse correlation between the expression of hsa-miR-596 and hsa-miR-224-5p and the aforementioned cytokines. Our findings underscore a robust association between blood cytokine and miRNA concentrations and the severity of MIS-C. These insights enhance our understanding of the genetic regulatory mechanisms implicated in MIS-C pathogenesis, offering potential avenues for early biomarker detection and therapy monitoring through miRNA analysis.
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Affiliation(s)
- Yun-Hao Tsai
- School of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Jun-Jie Hong
- Department of Taiwan Business Development, Inti Taiwan, Inc., Hsinchu, Taiwan
| | - Chao-Min Cheng
- Institute of Biomedical Engineering, College of Engineering, National Tsing Hua University, Hsinchu, Taiwan
| | - Mei-Hsiu Cheng
- Department of Taiwan Business Development, Inti Taiwan, Inc., Hsinchu, Taiwan
| | - Cheng-Han Chen
- Institute of Biomedical Engineering, College of Engineering, National Tsing Hua University, Hsinchu, Taiwan
- Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Min-Ling Hsieh
- Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng-Kung University, Tainan, Taiwan
| | - Kai-Sheng Hsieh
- Department of Pediatrics and Structural, Congenital Heart and Echocardiography Center, School of Medicine, China Medical University, Taichung, Taiwan
| | - Ching-Fen Shen
- Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng-Kung University, Tainan, Taiwan
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Bogdan M, Meca AD, Turcu-Stiolica A, Oancea CN, Kostici R, Surlin MV, Florescu C. Insights into the Relationship between Pentraxin-3 and Cancer. Int J Mol Sci 2022; 23:15302. [PMID: 36499628 PMCID: PMC9739619 DOI: 10.3390/ijms232315302] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 11/21/2022] [Accepted: 11/29/2022] [Indexed: 12/11/2022] Open
Abstract
Although cancer can be cured if detected early and treated effectively, it is still a leading cause of death worldwide. Tumor development can be limited by an appropiate immune response, but it can be promoted by chronic extensive inflammation through metabolic dysregulation and angiogenesis. In the past decade, numerous efforts have been made in order to identify novel candidates with predictive values in cancer diagnostics. In line with this, researchers have investigated the involvement of pentraxin-3 (PTX-3) in cellular proliferation and immune escape in various types of cancers, although it has not been clearly elucidated. PTX-3 is a member of the long pentraxin subfamily which plays an important role in regulating inflammation, innate immunity response, angiogenesis, and tissue remodeling. Increased synthesis of inflammatory biomarkers and activation of different cellular mechanisms can induce PTX-3 expression in various types of cells (neutrophils, monocytes, lymphocytes, myeloid dendritic cells, fibroblasts, and epithelial cells). PTX-3 has both pro- and anti-tumor functions, thus dual functions in oncogenesis. This review elucidates the potential usefulness of PTX-3 as a serum biomarker in cancer. While future investigations are needed, PTX-3 is emerging as a promising tool for cancer's diagnosis and prognosis, and also treatment monitoring.
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Affiliation(s)
- Maria Bogdan
- Department of Pharmacology, Faculty of Pharmacy, University of Medicine and Pharmacy, 200349 Craiova, Romania
| | - Andreea-Daniela Meca
- Department of Pharmacology, Faculty of Pharmacy, University of Medicine and Pharmacy, 200349 Craiova, Romania
| | - Adina Turcu-Stiolica
- Department of Pharmacoeconomics, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Carmen Nicoleta Oancea
- Department of Biochemistry, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Roxana Kostici
- Department of Toxicology, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Marin Valeriu Surlin
- Department of General Surgery, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Cristina Florescu
- Department of Cardiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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Zhang H, Wang R, Wang Z, Wu W, Zhang N, Zhang L, Hu J, Luo P, Zhang J, Liu Z, Feng S, Peng Y, Liu Z, Cheng Q. Molecular insight into pentraxin-3: Update advances in innate immunity, inflammation, tissue remodeling, diseases, and drug role. Biomed Pharmacother 2022; 156:113783. [PMID: 36240615 DOI: 10.1016/j.biopha.2022.113783] [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: 07/14/2022] [Revised: 09/28/2022] [Accepted: 09/28/2022] [Indexed: 11/20/2022] Open
Abstract
Pentraxin-3 (PTX3) is the prototype of the long pentraxin subfamily, an acute-phase protein consisting of a C-terminal pentraxin domain and a unique N-terminal domain. PTX3 was initially isolated from human umbilical vein endothelial cells and human FS-4 fibroblasts. It was subsequently found to be also produced by synoviocytes, chondrocytes, osteoblasts, smooth muscle cells, myeloid dendritic cells, epithelial cells, and tumor cells. Various modulatory factors, such as miRNAs, cytokines, drugs, and hypoxic conditions, could regulate the expression level of PTX3. PTX3 is essential in regulating innate immunity, inflammation, angiogenesis, and tissue remodeling. Besides, PTX3 may play dual (pro-tumor and anti-tumor) roles in oncogenesis. PTX3 is involved in the occurrence and development of many non-cancerous diseases, including COVID-19, and might be a potential biomarker indicating the prognosis, activity,and severity of diseases. In this review, we summarize and discuss the potential roles of PTX3 in the oncogenesis and pathogenesis of non-cancerous diseases and potential targeted therapies based on PTX3.
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Affiliation(s)
- Hao Zhang
- Department of Neurosurgery, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China; Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, China
| | - Ruixuan Wang
- Department of Oncology, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China
| | - Zeyu Wang
- Department of Neurosurgery, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China
| | - Wantao Wu
- Department of Oncology, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China
| | - Nan Zhang
- Department of Neurosurgery, Xiangya Hospital, Central South University, China; One-third Lab, College of Bioinformatics Science and Technology, Harbin Medical University, China
| | - Longbo Zhang
- Department of Neurosurgery, Xiangya Hospital, Central South University, China; Department of Neurosurgery, and Department of Cellular & Molecular Physiology,Yale University School of Medicine, USA; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China
| | - Jason Hu
- Department of Neonatology, Yale University School of Medicine, USA
| | - Peng Luo
- Department of Oncology, Zhujiang Hospital, Southern Medical University, China
| | - Jian Zhang
- Department of Oncology, Zhujiang Hospital, Southern Medical University, China
| | - Zaoqu Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, China
| | - Songshan Feng
- Department of Neurosurgery, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China
| | - Yun Peng
- Department of Geriatrics, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China
| | - Zhengzheng Liu
- Department of Oncology, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China.
| | - Quan Cheng
- Department of Neurosurgery, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China.
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Kim WR, Park EG, Lee YJ, Bae WH, Lee DH, Kim HS. Integration of TE Induces Cancer Specific Alternative Splicing Events. Int J Mol Sci 2022; 23:10918. [PMID: 36142830 PMCID: PMC9502224 DOI: 10.3390/ijms231810918] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 09/13/2022] [Accepted: 09/13/2022] [Indexed: 11/16/2022] Open
Abstract
Alternative splicing of messenger RNA (mRNA) precursors contributes to genetic diversity by generating structurally and functionally distinct transcripts. In a disease state, alternative splicing promotes incidence and development of several cancer types through regulation of cancer-related biological processes. Transposable elements (TEs), having the genetic ability to jump to other regions of the genome, can bring about alternative splicing events in cancer. TEs can integrate into the genome, mostly in the intronic regions, and induce cancer-specific alternative splicing by adjusting various mechanisms, such as exonization, providing splicing donor/acceptor sites, alternative regulatory sequences or stop codons, and driving exon disruption or epigenetic regulation. Moreover, TEs can produce microRNAs (miRNAs) that control the proportion of transcripts by repressing translation or stimulating the degradation of transcripts at the post-transcriptional level. Notably, TE insertion creates a cancer-friendly environment by controlling the overall process of gene expression before and after transcription in cancer cells. This review emphasizes the correlative interaction between alternative splicing by TE integration and cancer-associated biological processes, suggesting a macroscopic mechanism controlling alternative splicing by TE insertion in cancer.
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Affiliation(s)
- Woo Ryung Kim
- Department of Integrated Biological Sciences, Pusan National University, Busan 46241, Korea
- Institute of Systems Biology, Pusan National University, Busan 46241, Korea
| | - Eun Gyung Park
- Department of Integrated Biological Sciences, Pusan National University, Busan 46241, Korea
- Institute of Systems Biology, Pusan National University, Busan 46241, Korea
| | - Yun Ju Lee
- Department of Integrated Biological Sciences, Pusan National University, Busan 46241, Korea
- Institute of Systems Biology, Pusan National University, Busan 46241, Korea
| | - Woo Hyeon Bae
- Department of Integrated Biological Sciences, Pusan National University, Busan 46241, Korea
- Institute of Systems Biology, Pusan National University, Busan 46241, Korea
| | - Du Hyeong Lee
- Department of Integrated Biological Sciences, Pusan National University, Busan 46241, Korea
- Institute of Systems Biology, Pusan National University, Busan 46241, Korea
| | - Heui-Soo Kim
- Institute of Systems Biology, Pusan National University, Busan 46241, Korea
- Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Korea
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Park EG, Ha H, Lee DH, Kim WR, Lee YJ, Bae WH, Kim HS. Genomic Analyses of Non-Coding RNAs Overlapping Transposable Elements and Its Implication to Human Diseases. Int J Mol Sci 2022; 23:ijms23168950. [PMID: 36012216 PMCID: PMC9409130 DOI: 10.3390/ijms23168950] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 08/05/2022] [Accepted: 08/09/2022] [Indexed: 11/16/2022] Open
Abstract
It is estimated that up to 80% of the human genome is transcribed into RNA molecules but less than 2% of the genome encodes the proteins, and the rest of the RNA transcripts that are not translated into protein are called non-coding RNAs (ncRNAs). Many studies have revealed that ncRNAs have biochemical activities as epigenetic regulators at the post-transcriptional level. Growing evidence has demonstrated that transposable elements (TEs) contribute to a large percentage of ncRNAs’ transcription. The TEs inserted into certain parts of the genome can act as alternative promoters, enhancers, and insulators, and the accumulation of TEs increases genetic diversity in the human genome. The TEs can also generate microRNAs, so-called miRNA-derived from transposable elements (MDTEs), and are also implicated in disease progression, such as infectious diseases and cancer. Here, we analyzed the origin of ncRNAs and reviewed the published literature on MDTEs related to disease progression.
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Affiliation(s)
- Eun Gyung Park
- Department of Integrated Biological Sciences, Pusan National University, Busan 46241, Korea
- Institute of Systems Biology, Pusan National University, Busan 46241, Korea
| | - Hongseok Ha
- Division of Life Sciences, Korea University, Seoul 02841, Korea
| | - Du Hyeong Lee
- Department of Integrated Biological Sciences, Pusan National University, Busan 46241, Korea
- Institute of Systems Biology, Pusan National University, Busan 46241, Korea
| | - Woo Ryung Kim
- Department of Integrated Biological Sciences, Pusan National University, Busan 46241, Korea
- Institute of Systems Biology, Pusan National University, Busan 46241, Korea
| | - Yun Ju Lee
- Department of Integrated Biological Sciences, Pusan National University, Busan 46241, Korea
- Institute of Systems Biology, Pusan National University, Busan 46241, Korea
| | - Woo Hyeon Bae
- Department of Integrated Biological Sciences, Pusan National University, Busan 46241, Korea
- Institute of Systems Biology, Pusan National University, Busan 46241, Korea
| | - Heui-Soo Kim
- Institute of Systems Biology, Pusan National University, Busan 46241, Korea
- Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Korea
- Correspondence:
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Pentraxin 3 regulated by miR-224-5p modulates macrophage reprogramming and exacerbates osteoarthritis associated synovitis by targeting CD32. Cell Death Dis 2022; 13:567. [PMID: 35739102 PMCID: PMC9226026 DOI: 10.1038/s41419-022-04962-y] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 04/24/2022] [Accepted: 05/17/2022] [Indexed: 01/21/2023]
Abstract
Emerging evidence has shown an imbalance in M1/M2 macrophage polarization to play an essential role in osteoarthritis (OA) progression. However, the underlying mechanistic basis for this polarization is unknown. RNA sequencing of OA M1-polarized macrophages found highly expressed levels of pentraxin 3 (PTX3), suggesting a role for PTX3 in OA occurrence and development. Herein, PTX3 was found to be increased in the synovium and articular cartilage of OA patients and OA mice. Intra-articular injection of PTX3 aggravated, while PTX3 neutralization reversed synovitis and cartilage degeneration. No metabolic disorder or proteoglycan loss were observed in cartilage explants when treated with PTX3 alone. However, cartilage explants exhibited an OA phenotype when treated with culture supernatants of macrophages stimulated with PTX3, suggesting that PTX3 did not have a direct effect on chondrocytes. Therefore, the OA anti-chondrogenic effects of PTX3 are primarily mediated through macrophages. Mechanistically, PTX3 was upregulated by miR-224-5p deficiency, which activated the p65/NF-κB pathway to promote M1 macrophage polarization by targeting CD32. CD32 was expressed by macrophages, that when stimulated with PTX3, secreted abundant pro-inflammation cytokines that induced severe articular cartilage damage. The paracrine interaction between macrophages and chondrocytes produced a feedback loop that enhanced synovitis and cartilage damage. The findings of this study identified a functional pathway important to OA development. Blockade of this pathway and PTX3 may prevent and treat OA.
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Application Value of Real-Time Ultrasonic Elastograph with Serum Human Epididymis Protein 4, Interleukin-33, and Carbohydrate Antigen 153 in Diagnosis of Early Cervical Cancer. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:4880874. [PMID: 35449844 PMCID: PMC9018169 DOI: 10.1155/2022/4880874] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/15/2022] [Accepted: 04/02/2022] [Indexed: 02/02/2023]
Abstract
Objective To explore the application value of real-time ultrasonic elastograph (USE) with serum human epididymis protein 4 HE4, interleukin-33 (IL-33), and carbohydrate antigen 153 (CA153) in the diagnosis of early cervical cancer. Methods A total of 120 cervical cancer patients treated in our hospital (06, 2019-06, 2021) and meeting the study criteria were screened and divided into the benign group (BG, n = 70) and malignant group (MG, n = 50) according to their final diagnostic results, and healthy females who received physical examination in our hospital in the same period were selected as the control group (CG, n = 60). Patients in the three groups received real-time USE and detection of serum HE4, IL-33, and CA153 so as to analyze the diagnostic value of single examination and combined examination in diagnosing early cervical cancer. Results The patients' real-time USE score, E max, E mean, and elastic fibers were significantly higher in the MG than those in the BG (P < 0.05), and the patients' real-time USE E min, stroma ratio and collagen fibers were significantly lower in the MG than those in the BG (P < 0.05); the HE4, IL-33, and CA153 levels were obviously higher in the MG than those in the BG (P < 0.05) and were significantly higher in the BG than those in the CG (P < 0.05); the positive detection rate of combining real-time USE with serum HE4, IL-33, and CA153 was higher than that of single examination, and the diagnostic accuracy rate, sensitivity, specificity, positive predictive value, and negative predictive value of the combined examination were significantly higher than those of single examination (P < 0.05); according to the diagnostic efficacy of single examination and combined examination in diagnosing early cervical cancer by ROC curve, it was combined diagnosis > real-time USE > HE4 > CA153 > IL-33. Conclusion Combined examination of real-time USE and serum HE4, IL-33, and CA153 has higher diagnostic value in diagnosing early cervical cancer, which can obviously improve the diagnostic accuracy rate of cervical cancer.
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Mitra T, Elangovan S. Cervical cancer development, chemoresistance, and therapy: a snapshot of involvement of microRNA. Mol Cell Biochem 2021; 476:4363-4385. [PMID: 34453645 DOI: 10.1007/s11010-021-04249-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 08/17/2021] [Indexed: 12/24/2022]
Abstract
Cervical cancer (CC) is one of the leading causes of death in women due to cancer and a major concern in the developing world. Persistent human papilloma virus (HPV) infection is the major causative agent for CC. Besides HPV infection, genetic and epigenetic factors including microRNA (miRNA) also contribute to the malignant transformation. Earlier studies have revealed that miRNAs participate in cell proliferation, invasion and metastasis, angiogenesis, and chemoresistance processes by binding and inversely regulating the target oncogenes or tumor suppressor genes. Based on functions and mechanistic insights, miRNAs have been identified as cellular modulators that have an enormous role in diagnosis, prognosis, and cancer therapy. Signatures of miRNA could be used as diagnostic markers which are necessary for early diagnosis and management of CC. The therapeutic potential of miRNAs has been shown in CC; however, more comprehensive clinical trials are required for the clinical translation of miRNA-based diagnostics and therapeutics. Understanding the molecular mechanism of miRNAs and their target genes has been useful to develop miRNA-based therapeutic strategies for CC and overcome chemoresistance. In this review, we summarize the role of miRNAs in the development, progression, and metastasis of CC as well as chemoresistance. Further, we discuss the diagnostic and therapeutic potential of miRNAs to overcome chemoresistance and treatment of CC.
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Affiliation(s)
- Tandrima Mitra
- School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), Deemed To Be University, Bhubaneswar, Odisha, 751024, India
| | - Selvakumar Elangovan
- School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), Deemed To Be University, Bhubaneswar, Odisha, 751024, India.
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Chang X, Li D, Liu C, Zhang Z, Wang T. Pentraxin 3 is a diagnostic and prognostic marker for ovarian epithelial cancer patients based on comprehensive bioinformatics and experiments. Cancer Cell Int 2021; 21:193. [PMID: 33952272 PMCID: PMC8097951 DOI: 10.1186/s12935-021-01854-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 02/20/2021] [Accepted: 02/24/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Ovarian epithelial cancer is one of the leading malignant tumors in gynecology and lacks effective diagnostic and prognostic markers. Our study aims to screen and verify ovarian epithelial cancer biomarkers. METHODS GSE18520 and GSE26712 were downloaded from the GEO database. The "limma" and "WGCNA" packages were used to explore hub genes. The Kaplan-Meier Plotter database was used for survival analysis of the hub genes. Immunohistochemical analysis was used to identify the expression level of Pentraxin 3 in ovarian epithelial cancer samples. RESULTS In this study, we integrated and analyzed two datasets, GSE18520 and GSE26712, and a total of 238 differentially expressed genes (DEGs) were screened out. Enrichment analysis showed that these DEGs were related to collagen-containing extracellular matrix and other pathways. Further application of WGCNA (weighted gene coexpression network analysis) identified 15 gene modules, with the purple module showing the highest correlation with ovarian epithelial cancer. Twenty-five genes were shared between the purple module and DEGs, 13 genes were related to the prognosis of ovarian epithelial cancer patients, and the PTX3 gene had the highest hazardous risk (HR) value. We performed immunohistochemical analyses on the 255 Pentraxin-3 (PTX3)-based clinical samples. PTX3 was found to be overexpressed in ovarian epithelial cancer and related to the degree of differentiation. The Cox proportional hazard model indicates that high PTX3 expression is an independent risk factor for the prognosis of ovarian epithelial cancer patients. CONCLUSIONS In conclusion, through WGCNA and a series of comprehensive bioinformatics analyses, PTX3 was first identified as a novel diagnostic and prognostic biomarker for ovarian epithelial cancer.
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Affiliation(s)
- Xiaoying Chang
- Department of Pathology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping, Shenyang, 110004, China
| | - Dan Li
- Department of Pathology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping, Shenyang, 110004, China
| | - Chang Liu
- Department of Pathology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping, Shenyang, 110004, China
| | - Zhe Zhang
- Department of Pathology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping, Shenyang, 110004, China
| | - Tao Wang
- Department of Pathology, Shenyang KingMed Center for Clinical Laboratory Co., Ltd, Shenyang, 110164, China.
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Sabeena S, Ravishankar N. Role of microRNAs in Predicting the Prognosis of Cervical Cancer Cases: A Systematic Review and Meta-Analysis. Asian Pac J Cancer Prev 2021; 22:999-1006. [PMID: 33906290 PMCID: PMC8325113 DOI: 10.31557/apjcp.2021.22.4.999] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Indexed: 12/02/2022] Open
Abstract
Aim: There is growing evidence for the possible use of microRNAs (miRNAs) in cancers as diagnostic as well as prognostic biomarkers in the present era of Personalized Medicine. The objective of the present systematic review and meta-analysis was to assess the prognostic role of microRNAs in uterine cervical cancers. Methods: A systematic review and meta-analysis was carried out searching electronic databases for published articles between January 2009 and August 2020 based on standard systematic review guidelines. Meta-analysis was performed by pooling the hazard ratio (HR) with 95% confidence interval (CI) to assess the prognostic value of deregulated miRNAs by the random-effects model. Results: In the present meta-analysis, the aberrant expression of 14 microRNAs in 1,526 uterine cervical cancer cases before definitive therapy from 14 case-control studies were assessed. The pooled HR of two miRNAs, miRNA-155 and miRNA-224 which were upregulated in cervical cancer tissues was 1.76 (95% CI 1.27-2.45) revealing significant association with overall poor survival. Meanwhile, the pooled HR was 1.53 (95% CI 0.94-2.94) when all the deregulated miRNAs in cervical cancer tissues were evaluated. The pooled HR of downregulated miRNAs was 1.46 (95% CI 0.81, 2.64). Meanwhile, the pooled HR of three upregulated miRNAs-425-5p, 196a, 205 in the serum sample was 1.37 (95% CI 0.45 -4.20). Conclusion: The downregulation of aberrant miRNAs was not associated with poor overall survival rates.
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Affiliation(s)
| | - Nagaraja Ravishankar
- Department of Biostatistics, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India
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12
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Bakır E, Çal T, Aydın Dilsiz S, Canpınar H, Eken A, Ündeğer Bucurgat Ü. Assessment of the cytotoxic, genotoxic, and apoptotic potential of flurbiprofen in HeLa and HepG2 cell lines. J Biochem Mol Toxicol 2021; 35:1-11. [PMID: 33709623 DOI: 10.1002/jbt.22770] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 12/14/2020] [Accepted: 03/02/2021] [Indexed: 11/07/2022]
Abstract
In the literature, the anticancer potential of flurbiprofen isn't fully understood. In this study, the cytotoxic, genotoxic, and apoptotic effects of flurbiprofen were evaluated in human cervical and liver cancer cells. Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and it was observed that cytotoxicity increased in a concentration- and time-dependent manner. Genotoxicity was determined using alkaline Comet assay. DNA damage increased in a concentration-dependent manner. Early apoptosis was evaluated using real-time polymerase chain reaction, and it was found that apoptotic gene levels increased while antiapoptotic gene levels decreased. Late apoptosis and cell cycle analyzes were determined using flow cytometry. No evidence of late apoptosis was observed, and no significant arrest was found in the cell cycle. In conclusion, it seems that flurbiprofen has a cytotoxic, genotoxic, and apoptotic effects in both human cancer cell lines. Moreover, the findings indicate that flurbiprofen is effective at the gene level and induces apoptosis with an intracellular pathway.
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Affiliation(s)
- Elçin Bakır
- Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey
| | - Tuğbagül Çal
- Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
| | - Sevtap Aydın Dilsiz
- Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
| | - Hande Canpınar
- Department of Basic Oncology, Institute of Cancer, Hacettepe University, Ankara, Turkey
| | - Ayşe Eken
- Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey
| | - Ülkü Ündeğer Bucurgat
- Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
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13
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Wei H, Wang X, Niu X, Jiao R, Li X, Wang S. miR‑34c‑5p targets Notch1 and suppresses the metastasis and invasion of cervical cancer. Mol Med Rep 2020; 23:120. [PMID: 33300051 PMCID: PMC7751466 DOI: 10.3892/mmr.2020.11759] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 10/16/2020] [Indexed: 12/11/2022] Open
Abstract
Micro (mi)RNAs are crucial participants in the progression of cervical cancer (CC). Growing evidence indicates that miRNA (miR)-34c-5p is a pivotal tumor suppressor in numerous types of cancer and its functions in CC require further investigating. The present study demonstrated that there was a decreased level of miR-34c-5p in CC-associated cell lines compared with healthy control samples. It also demonstrated that miR-34c-5p targeted Notch1 and suppressed CC progression. Dual-Luciferase reporter assays verified the targeted relationship of miR-34c-5p and Notch1. The expression of Notch1 in HeLa cells was markedly reduced following miR-34c-5p overexpression and the proliferation, migration and invasion of HeLa cells were reduced although apoptosis was accelerated. However, overexpression of miR-34c-5p was reversed following the addition of Notch1, which supported the finding of the targeted relationship between miR-34c-5p and Notch1. Flow cytometry demonstrated that miR-34c-5p inhibited the proliferation of HeLa cells while accelerating apoptosis. The present study concluded that miR-34c-5p was a tumor suppressor in CC and may be a novel measure for the future treatment of CC.
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Affiliation(s)
- Huali Wei
- Department of Gynecology and Obstetrics, Emergency General Hospital, Beijing 100028, P.R. China
| | - Xiaolan Wang
- Department of Gynecology and Obstetrics, Emergency General Hospital, Beijing 100028, P.R. China
| | - Xiumin Niu
- Department of Gynecology and Obstetrics, Emergency General Hospital, Beijing 100028, P.R. China
| | - Ruili Jiao
- Department of Gynecology and Obstetrics, Chaoyang District Maternal and Child Health Hospital, Beijing 100020, P.R. China
| | - Xiaojuan Li
- Department of Medical Records and Statistics, Emergency General Hospital, Beijing 100028, P.R. China
| | - Sumei Wang
- Department of Gynecology and Obstetrics, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China
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14
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Zheng Q, Yu JJ, Li C, Li J, Wang J, Wang S. miR-224 targets BTRC and promotes cell migration and invasion in colorectal cancer. 3 Biotech 2020; 10:485. [PMID: 33117626 PMCID: PMC7585582 DOI: 10.1007/s13205-020-02477-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 10/12/2020] [Indexed: 12/15/2022] Open
Abstract
Our study aims to investigate the impact of miR-224 on cell migration and invasion in colorectal cancer (CRC) as well as its molecular mechanisms. The results showed that miR-224 was significantly upregulated in CRC compared to normal tissues via the TCGA database. Overexpression of miR-224 promoted CRC cell migration and invasion, while inhibition of miR-224 demonstrated the opposite result via transwell assays. In addition, we found that BTRC was a target gene of miR-224 through the miRecords database and dual-luciferase assay, while western blot together with RT-qPCR showed that inhibition of miR-224 led to elevated BTRC expression in protein level but not in mRNA level, and also decreased the expression of β-catenin. In reference to the Human Protein Atlas, BTRC protein expression was higher in normal tissues than in CRC tissues. In conclusion, miR-224 regulates its target BTRC protein expression and its related Wnt/β-catenin pathway. Its impact on cell migration and invasion in CRC cells suggested that miR-224 could be a prospective therapeutic target for early-stage non-metastatic CRC.
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Affiliation(s)
- Qi Zheng
- Department of Pathology, School of Basic Medical Sciences, Fudan University, 131 Dong’an Road, Shanghai, 200032 Shanghai China
| | - Jane J. Yu
- Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267 USA
| | - Chenggang Li
- State Key Laboratory of Medical Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China
| | - Jiali Li
- Department of Pathology, Huashan Hospital, Fudan University, Shanghai, China
| | - Jiping Wang
- Division of Surgical Oncology, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA USA
| | - Shuyang Wang
- Department of Pathology, School of Basic Medical Sciences, Fudan University, 131 Dong’an Road, Shanghai, 200032 Shanghai China
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15
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Meng F, Ou J, Liu J, Li X, Meng Y, Yan L, Deng P, Sun B. MicroRNA-877 is downregulated in cervical cancer and directly targets MACC1 to inhibit cell proliferation and invasion. Exp Ther Med 2019; 18:3650-3658. [PMID: 31602243 DOI: 10.3892/etm.2019.7989] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 08/02/2019] [Indexed: 12/13/2022] Open
Abstract
Previously, a number of microRNAs (miRNAs) have been reported to be dysregulated in cervical cancer, and dysregulated miRNAs may play crucial roles in the development and progression of cervical cancer. Hence, investigating the detailed roles of miRNAs that are aberrantly expressed in cervical cancer and the underlying molecular mechanisms is essential for early diagnosis and effective therapeutic approaches. miRNA-877 (miR-877) was found to be downregulated in hepatocellular carcinoma and renal cell carcinoma, and function as a tumor-suppressive miRNA. However, how miR-877 exerts an effect in cervical cancer progression and its underlying molecular mechanisms remains to be elucidated. In the current study, reverse transcription-quantitative PCR was performed to determine miR-877 expression in cervical cancer tissues and cell lines. The effects of miR-877 overexpression on cervical cancer cell proliferation and invasion were evaluated using MTT and Transwell cell invasion assays. In the present study, miR-877 was significantly downregulated in cervical cancer tissues and cell lines, and the decreased expression levels of miR-877 were significantly associated with increased International Federation of Gynecology and Obstetric stage as well as increased lymph node metastasis in patients with cervical cancer. Upregulation of miR-877 using miR-877 mimics resulted in the decreased proliferation and invasion of cervical cancer cells. Metastasis-associated in colon cancer-1 (MACC1) was assessed using bioinformatics analyses to determine whether it could be a potential target gene of miR-877, and the results were confirmed using a luciferase reporter assay. Furthermore, MACC1 was markedly upregulated in cervical cancer tissues, and its level was negatively correlated with the miR-877 level. Overexpression of miR-877 resulted in decreased expression levels of MACC1 in cervical cancer cells at both the mRNA and protein levels. In addition, the functional effects of MACC1 knockdown were similar to those induced by upregulated miR-877 in cervical cancer cells. MACC1 restored miR-877 overexpression-mediated suppression of cervical cancer cell proliferation and invasion. In conclusion, miR-877 may play an antitumor role in cervical cancer by directly targeting MACC1, which suggests that this miRNA may be a promising therapeutic target for the treatment of patients with such an aggressive gynecological cancer.
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Affiliation(s)
- Fanxu Meng
- Department of Radiotherapy, Jilin Cancer Hospital, Changchun, Jilin 130012, P.R. China
| | - Jian Ou
- Department of Radiotherapy, Jilin Cancer Hospital, Changchun, Jilin 130012, P.R. China
| | - Jinyu Liu
- Department of Radiotherapy, Jilin Cancer Hospital, Changchun, Jilin 130012, P.R. China
| | - Xindi Li
- Department of Radiotherapy, Jilin Cancer Hospital, Changchun, Jilin 130012, P.R. China
| | - Yanli Meng
- Department of Radiotherapy, Jilin Cancer Hospital, Changchun, Jilin 130012, P.R. China
| | - Ling Yan
- Department of Radiotherapy, Jilin Cancer Hospital, Changchun, Jilin 130012, P.R. China
| | - Ping Deng
- Department of Radiotherapy, Jilin Cancer Hospital, Changchun, Jilin 130012, P.R. China
| | - Baosheng Sun
- Department of Radiotherapy, Jilin Cancer Hospital, Changchun, Jilin 130012, P.R. China
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16
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Wang S, Gao B, Yang H, Liu X, Wu X, Wang W. MicroRNA-432 is downregulated in cervical cancer and directly targets FN1 to inhibit cell proliferation and invasion. Oncol Lett 2019; 18:1475-1482. [PMID: 31423213 DOI: 10.3892/ol.2019.10403] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 04/04/2019] [Indexed: 12/15/2022] Open
Abstract
Numerous studies have identified the dysregulation of microRNAs (miRNAs) in cervical cancer, and dysregulated miRNAs are involved in regulating a number of tumour- associated biological behaviours. Therefore, investigating the roles of cervical cancer-associated miRNAs and the underlying molecular mechanisms is essential for the development of novel diagnostic biomarkers and effective therapeutic targets. MicroRNA-432 (miR-432) dysregulation has been revealed to be implicated in the carcinogenesis and progression of a number of types of human cancer. However, the effects and underlying molecular mechanisms of miR-432 in cervical cancer have yet to be elucidated. In the present study, miR-432 expression was determined using reverse transcription-quantitative polymerase chain reaction. The results revealed that miR-432 was expressed at low levels in cervical cancer tissues and cell lines. Decreased miR-432 expression was significantly associated with the International Federation of Gynecology and Obstetrics stage, myometrium invasion and lymph node metastasis of patients with cervical cancer. Following transfection with miR-432 mimic, the expression of miR-432 was significantly upregulated in cervical cancer cells. Upregulation of miR-432 expression restricted the proliferation and invasion of cervical cancer cells. Bioinformatics analysis followed by luciferase reporter assays revealed that fibronectin 1 (FN1) was a direct target gene of miR-432 in cervical cancer cells. In addition, FN1 was upregulated in cervical cancer tissues and was inversely correlated with miR-432 levels. Furthermore, miR-432 upregulation decreased the expression levels of FN1 in cervical cancer cells at the mRNA and protein levels. Furthermore, silencing of FN1 could stimulate the tumour suppressor effects of miR-432 upregulation in cervical cancer cells. In addition, restored FN1 expression neutralized the effects of miR-432 overexpression in cervical cancer cells. The results of the present study indicate that miR-432 is a tumour suppressor that can restrain the aggressive phenotype of cervical cancer cells by directly targeting FN1, suggesting that this miRNA may be developed as an effective therapeutic strategy for patients with cervical cancer.
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Affiliation(s)
- Shanzong Wang
- Department of Pathology, The Third People's Hospital of Linyi, Linyi, Shandong 276023, P.R. China
| | - Baohong Gao
- Department of Gynecology, The Third People's Hospital of Linyi, Linyi, Shandong 276023, P.R. China
| | - Hailin Yang
- Department of Oncology, The Third People's Hospital of Linyi, Linyi, Shandong 276023, P.R. China
| | - Xuejian Liu
- Department of Oncology, The Third People's Hospital of Linyi, Linyi, Shandong 276023, P.R. China
| | - Xia Wu
- Department of Oncology, The Third People's Hospital of Linyi, Linyi, Shandong 276023, P.R. China
| | - Weijuan Wang
- Department of Gynecology, The Third People's Hospital of Linyi, Linyi, Shandong 276023, P.R. China
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17
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Cui Y, Xu HF, Liu MY, Xu YJ, He JC, Zhou Y, Cang SD. Mechanism of exosomal microRNA-224 in development of hepatocellular carcinoma and its diagnostic and prognostic value. World J Gastroenterol 2019; 25:1890-1898. [PMID: 31057302 PMCID: PMC6478613 DOI: 10.3748/wjg.v25.i15.1890] [Citation(s) in RCA: 79] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Revised: 02/17/2019] [Accepted: 02/23/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Exosomes contain proteins, lipids, and biological molecules such as DNA and RNA. Nucleic acids in exosomes are a group of molecules that can act as biomarkers. Currently, there are many reports on exosomal microRNAs, which are ideal biomarkers for the early diagnosis of cancer. However, there are few reports on the role of exosomal microRNAs in the diagnosis and prognosis of hepatocellular carcinoma (HCC).
AIM To understand the mechanism of exosomal microRNA-224 (miR-224) in the development of HCC and evaluate its diagnostic and prognostic value.
METHODS Cell culture and transfection of exosomal miRNA-224, real-time quantitative PCR, luciferase reporter assay, and other methods were used to find new biomarkers related to the development of HCC that can be used to diagnose HCC and predict HCC prognosis.
RESULTS By targeting glycine N-methyltransferase, incubating exosomes with miR-224 mimic resulted in a significant increase in cell proliferation compared to that of the control group, while incubation with the miR-224 inhibitor significantly reduced cell proliferation. The same results were obtained for the cell invasion assay. Serum exosomal miR-224 did have some ability to differentiate patients with HCC from healthy controls, with an area under the curve of 0.910, and HCC patients with higher serum exosomal miR-224 expression had lower overall survival.
CONCLUSION Exosomal miR-224 is a tumor promotor and can be a marker of diagnosis and prognosis of HCC patients, however, its ability to distinguish liver diseases needs further verification.
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MESH Headings
- 3' Untranslated Regions/genetics
- Adult
- Aged
- Aged, 80 and over
- Biomarkers, Tumor/blood
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinogenesis/genetics
- Carcinoma, Hepatocellular/blood
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/mortality
- Cell Line, Tumor
- Cell Proliferation/genetics
- Exosomes/metabolism
- Female
- Gene Expression Regulation, Neoplastic
- Glycine N-Methyltransferase/genetics
- Glycine N-Methyltransferase/metabolism
- Humans
- Kaplan-Meier Estimate
- Liver Neoplasms/blood
- Liver Neoplasms/diagnosis
- Liver Neoplasms/genetics
- Liver Neoplasms/mortality
- Male
- MicroRNAs/blood
- MicroRNAs/genetics
- MicroRNAs/metabolism
- Middle Aged
- Prognosis
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Affiliation(s)
- Yao Cui
- Department of Oncology, Henan Key Laboratory for Precision Medicine in Cancer, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou 450003, Henan Province, China
| | - Hai-Feng Xu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Interventional Therapy Department, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Ming-Yue Liu
- Department of Oncology, Henan Key Laboratory for Precision Medicine in Cancer, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou 450003, Henan Province, China
| | - Yu-Jie Xu
- Department of Oncology, Henan Key Laboratory for Precision Medicine in Cancer, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou 450003, Henan Province, China
| | - Jun-Chuang He
- Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou 450003, Henan Province, China
| | - Yun Zhou
- Department of Oncology, Henan Key Laboratory for Precision Medicine in Cancer, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou 450003, Henan Province, China
| | - Shun-Dong Cang
- Department of Oncology, Henan Key Laboratory for Precision Medicine in Cancer, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou 450003, Henan Province, China
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