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Zhu X, Yang T, Zheng Y, Nie Q, Chen J, Li Q, Ren X, Yin X, Wang S, Yan Y, Liu Z, Wu M, Lu D, Yu Y, Chen L, Chatterjee E, Li G, Cretoiu D, Bowen TS, Li J, Xiao J. EIF4A3-Induced Circular RNA CircDdb1 Promotes Muscle Atrophy through Encoding a Novel Protein CircDdb1-867aa. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2406986. [PMID: 39412095 PMCID: PMC11615752 DOI: 10.1002/advs.202406986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 09/22/2024] [Indexed: 12/06/2024]
Abstract
Little is known about if and how circular RNAs (circRNAs) are involved in skeletal muscle atrophy. Here a conserved circular RNA Damage-specific DNA binding protein 1 (circDdb1), derived from the host gene encoding Damage-specific DNA binding protein 1 (DDB1), as a mechanism of muscle atrophy is identified. circDdb1 expression is markedly increased in a variety of muscle atrophy types in vivo and in vitro, and human aging muscle. Both in vivo and in vitro, ectopic expression of circDdb1 causes muscle atrophy. In contrast, multiple forms of muscle atrophy caused by dexamethasone, tumor necrosis factor-alpha (TNF-α), or angiotensin II (Ang II) in myotube cells, as well as by denervation, angiotensin II, and immobility in mice, are prevented by circDdb1 inhibition. Eukaryotic initiation factor 4A3 (EIF4A3) is identified as a regulator of circDdb1 expression in muscle atrophy, whereas circDdb1 encodes a novel protein, circDdb1-867aa. circDdb1-867aa binds with and increases the phosphorylation level of eukaryotic elongation factor 2 (eEF2) at Thr56 to reduce protein translation and promote muscle atrophy. In summary, these findings establish circDdb1 as a shared regulator of muscle atrophy across multiple diseases and a potential therapeutic target.
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Affiliation(s)
- Xiaolan Zhu
- Cardiac Regeneration and Ageing LabInstitute of Geriatrics (Shanghai University)Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life SciencesShanghai UniversityNantong226011China
- Institute of Cardiovascular SciencesShanghai Engineering Research Center of Organ RepairJoint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education)School of Life SciencesShanghai UniversityShanghai200444China
| | - Tingting Yang
- Cardiac Regeneration and Ageing LabInstitute of Geriatrics (Shanghai University)Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life SciencesShanghai UniversityNantong226011China
- Institute of Cardiovascular SciencesShanghai Engineering Research Center of Organ RepairJoint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education)School of Life SciencesShanghai UniversityShanghai200444China
| | - Yongjun Zheng
- Division of Pain ManagementHuadong Hospital Affiliated to Fudan UniversityShanghai200040China
| | - Qiumeng Nie
- Cardiac Regeneration and Ageing LabInstitute of Geriatrics (Shanghai University)Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life SciencesShanghai UniversityNantong226011China
- Institute of Cardiovascular SciencesShanghai Engineering Research Center of Organ RepairJoint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education)School of Life SciencesShanghai UniversityShanghai200444China
| | - Jingying Chen
- Cardiac Regeneration and Ageing LabInstitute of Geriatrics (Shanghai University)Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life SciencesShanghai UniversityNantong226011China
- Institute of Cardiovascular SciencesShanghai Engineering Research Center of Organ RepairJoint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education)School of Life SciencesShanghai UniversityShanghai200444China
| | - Qian Li
- Cardiac Regeneration and Ageing LabInstitute of Geriatrics (Shanghai University)Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life SciencesShanghai UniversityNantong226011China
- Institute of Cardiovascular SciencesShanghai Engineering Research Center of Organ RepairJoint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education)School of Life SciencesShanghai UniversityShanghai200444China
| | - Xinyi Ren
- Cardiac Regeneration and Ageing LabInstitute of Geriatrics (Shanghai University)Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life SciencesShanghai UniversityNantong226011China
- Institute of Cardiovascular SciencesShanghai Engineering Research Center of Organ RepairJoint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education)School of Life SciencesShanghai UniversityShanghai200444China
| | - Xiaohang Yin
- Cardiac Regeneration and Ageing LabInstitute of Geriatrics (Shanghai University)Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life SciencesShanghai UniversityNantong226011China
- Institute of Cardiovascular SciencesShanghai Engineering Research Center of Organ RepairJoint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education)School of Life SciencesShanghai UniversityShanghai200444China
| | - Siqi Wang
- Cardiac Regeneration and Ageing LabInstitute of Geriatrics (Shanghai University)Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life SciencesShanghai UniversityNantong226011China
- Institute of Cardiovascular SciencesShanghai Engineering Research Center of Organ RepairJoint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education)School of Life SciencesShanghai UniversityShanghai200444China
| | - Yuwei Yan
- Cardiac Regeneration and Ageing LabInstitute of Geriatrics (Shanghai University)Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life SciencesShanghai UniversityNantong226011China
- Institute of Cardiovascular SciencesShanghai Engineering Research Center of Organ RepairJoint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education)School of Life SciencesShanghai UniversityShanghai200444China
| | - Zhengyu Liu
- Cardiac Regeneration and Ageing LabInstitute of Geriatrics (Shanghai University)Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life SciencesShanghai UniversityNantong226011China
- Institute of Cardiovascular SciencesShanghai Engineering Research Center of Organ RepairJoint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education)School of Life SciencesShanghai UniversityShanghai200444China
| | - Ming Wu
- Department of OrthopedicsShanghai Gongli HospitalShanghai200135China
| | - Dongchao Lu
- School of Integrative MedicineShanghai University of Traditional Chinese MedicineShanghai201203China
| | - Yan Yu
- Department of Spine SurgeryTongji HospitalSchool of MedicineTongji UniversityShanghai200065China
| | - Lei Chen
- Department of Spine SurgeryTongji HospitalSchool of MedicineTongji UniversityShanghai200065China
| | - Emeli Chatterjee
- Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical SchoolBostonMA02114USA
| | - Guoping Li
- Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical SchoolBostonMA02114USA
| | - Dragos Cretoiu
- Department of Medical GeneticsCarol Davila University of Medicine and PharmacyBucharest020031Romania
- Materno‐Fetal Assistance Excellence UnitAlessandrescu‐Rusescu National Institute for Mother and Child HealthBucharest011062Romania
| | - T Scott Bowen
- School of Biomedical SciencesFaculty of Biological SciencesUniversity of LeedsLeedsLS2 9JTUK
| | - Jin Li
- Cardiac Regeneration and Ageing LabInstitute of Geriatrics (Shanghai University)Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life SciencesShanghai UniversityNantong226011China
- Institute of Cardiovascular SciencesShanghai Engineering Research Center of Organ RepairJoint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education)School of Life SciencesShanghai UniversityShanghai200444China
| | - Junjie Xiao
- Cardiac Regeneration and Ageing LabInstitute of Geriatrics (Shanghai University)Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life SciencesShanghai UniversityNantong226011China
- Institute of Cardiovascular SciencesShanghai Engineering Research Center of Organ RepairJoint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education)School of Life SciencesShanghai UniversityShanghai200444China
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Hua M, Chen Y, Jia M, Lv W, Xu Y, Zhang Y. RNA-binding protein THUMPD2 inhibits proliferation and promotes metastasis in epithelial ovarian cancer. Heliyon 2024; 10:e33201. [PMID: 39071668 PMCID: PMC11279259 DOI: 10.1016/j.heliyon.2024.e33201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 06/13/2024] [Accepted: 06/17/2024] [Indexed: 07/30/2024] Open
Abstract
Ovarian cancer (OC) is a common and lethal gynaecological malignancy. RNA-binding proteins (RBPs) play a crucial role in governing RNA metabolism and have been implicated in the development and progression of diverse cancer types. Slight alterations in RBPs' expression or activity can induce substantial modifications in the regulatory network. THUMPD2, as member of the RBP family, was found to have differential expression in ovarian cancer, with the mechanism has not been studied yet. In this study, THUMPD2 protein was found to be weakly expressed in the early (I + II) stages of OC (P = 0.013), with a low expression rate of 78.6 %, and highly expressed in late (III + IV) stages (P = 0.009), with a high expression rate of 84.8 %. The shRNA-mediated knockdown of THUMPD2 in OVCAR3 and SKOV3 cells resulted in increased cell proliferation but inhibited metastasis, whereas THUMPD2 overexpression had the opposite effect. THUMPD2 overexpression suppressed tumour growth in vivo. Conversely, low THUMPD2 expression promoted tumour growth. Furthermore, we identified the potential target genes and pathways of THUMPD2 using GO and KEGG analyses, which were related to the centrosome, microtubules, cell cycle, and extracellular matrix. We demonstrated that low expression of THUMPD2 in the early stage promoted tumour growth and high expression in the late stage promoted tumour metastasis. Our findings reveal the dual function of THUMPD2 in OC and suggest that THUMPD2 may serve as a therapeutic target for the treatment of OC.
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Affiliation(s)
- Minhui Hua
- Suzhou Medical College of Soochow University, Suzhou, 215123, China
- Department of Gynecology and Obstetrics, Affiliated Hospital of Nantong University, Nantong, 226001, China
| | - Yujie Chen
- Department of Gynecology and Obstetrics, Affiliated Hospital of Nantong University, Nantong, 226001, China
| | - Meiqun Jia
- Department of Gynecology, Affiliated Tumor Hospital of Nantong University, Nantong, 226001, China
| | - Wenxuan Lv
- Department of Gynecology and Obstetrics, Affiliated Hospital of Nantong University, Nantong, 226001, China
| | - Yunzhao Xu
- Department of Gynecology and Obstetrics, Affiliated Hospital of Nantong University, Nantong, 226001, China
| | - Yuquan Zhang
- Suzhou Medical College of Soochow University, Suzhou, 215123, China
- Department of Gynecology and Obstetrics, Affiliated Hospital of Nantong University, Nantong, 226001, China
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Thamjamrassri P, Ariyachet C. Circular RNAs in Cell Cycle Regulation of Cancers. Int J Mol Sci 2024; 25:6094. [PMID: 38892280 PMCID: PMC11173060 DOI: 10.3390/ijms25116094] [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: 04/28/2024] [Revised: 05/26/2024] [Accepted: 05/29/2024] [Indexed: 06/21/2024] Open
Abstract
Cancer has been one of the most problematic health issues globally. Typically, all cancers share a common characteristic or cancer hallmark, such as sustaining cell proliferation, evading growth suppressors, and enabling replicative immortality. Indeed, cell cycle regulation in cancer is often found to be dysregulated, leading to an increase in aggressiveness. These dysregulations are partly due to the aberrant cellular signaling pathway. In recent years, circular RNAs (circRNAs) have been widely studied and classified as one of the regulators in various cancers. Numerous studies have reported that circRNAs antagonize or promote cancer progression through the modulation of cell cycle regulators or their associated signaling pathways, directly or indirectly. Mostly, circRNAs are known to act as microRNA (miRNA) sponges. However, they also hold additional mechanisms for regulating cellular activity, including protein binding, RNA-binding protein (RBP) recruitment, and protein translation. This review will discuss the current knowledge of how circRNAs regulate cell cycle-related proteins through the abovementioned mechanisms in different cancers.
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Affiliation(s)
- Pannathon Thamjamrassri
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand;
- Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
- Medical Biochemistry Program, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Chaiyaboot Ariyachet
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand;
- Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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Gao Y, Qiao X, Liu Z, Zhang W. The role of E2F2 in cancer progression and its value as a therapeutic target. Front Immunol 2024; 15:1397303. [PMID: 38807594 PMCID: PMC11130366 DOI: 10.3389/fimmu.2024.1397303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 04/30/2024] [Indexed: 05/30/2024] Open
Abstract
The E2F family of transcription factors plays a crucial role in the regulation of cell cycle progression and cell proliferation. Accumulative evidence indicates that aberrant expression or activation of E2F2 is a common phenomenon in malignances. E2F2 has emerged as a key player in the development and progression of various types of tumors. A wealth of research has substantiated that E2F2 could contribute to the enhancement of tumor cell proliferation, angiogenesis, and invasiveness. Moreover, E2F2 exerts its influence on a myriad of cellular processes by engaging with a spectrum of auxiliary factors and downstream targets, including apoptosis and DNA repair. The dysregulation of E2F2 in the context of carcinogenesis may be attributable to a multitude of mechanisms, which encompass modifications in upstream regulatory elements or epigenetic alterations. This review explores the function of E2F2 in cancer progression and both established and emerging therapeutic strategies aiming at targeting this oncogenic pathway, while also providing a strong basis for further research on the biological function and clinical applications of E2F2.
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Affiliation(s)
- Yang Gao
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Xinjie Qiao
- Department of Rhinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhenhui Liu
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Wenzhou Zhang
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
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Chen T, Li Z, Chen J, Xu Z. Circ_0000877 accelerates proliferation and immune escape of non-small cell lung cancer cells by regulating microRNA-637/E2F2 axis. ENVIRONMENTAL TOXICOLOGY 2024; 39:2980-2992. [PMID: 38317501 DOI: 10.1002/tox.24172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 01/14/2024] [Accepted: 01/26/2024] [Indexed: 02/07/2024]
Abstract
BACKGROUND Recently, circular RNA (circRNA) has become a vital targeted therapy gene for non-small-cell lung cancer (NSCLC) cells. CircRNA_0000877 (Circ_0000877) has been researched in diffuse large B-cell lymphoma (DLBCL). However, whether circ_0000877 regulated NSCLC cell progression is still poorly investigated. The research attempted to investigate the influence of circ_0000877 in NSCLC. METHODS Circ_0000877 levels in NSCLC tissues and cell lines were determined applying RT-qPCR. Cell functions were evaluated by CCK-8, EdU, flow cytometry, ELISA, and western blot. Gene interactions were predicted by Cirular RNA interactome database and Target Scan website and certified by dual-luciferase reporter, RIP, and RNA pull-down assays. Finally, mice experimental model was established to explore the effects of circ_0000877 on tumor growth in vivo. RESULTS The elevated trend of circ_0000877 expression was discovered in NSCLC tissues compared to para-carcinoma tissues. The clinicopathological data uncovered that up-regulated circ_0000877 was linked to tumor size, differentiation, and TNM stages of NSCLC patients. Knockdown of circ_0000877 inhibited the proliferation, triggered apoptosis, and prohibited immune escape in NSCLC cells. It was certified that miR-637 was directly interacted with circ_0000877 and targeted by E2F2. Overexpressed E2F2 strongly overturned the functions of circ_0000877 knockdown in NSCLC cells. Mice experimental data demonstrated that circ_0000877 knockdown suppressed tumor growth in vivo. CONCLUSION The research demonstrated that circ_0000877 exhibited the promotive effect on NSCLC cells proliferation and immune escape by regulating miR-637/E2F2 axis.
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Affiliation(s)
- Ting'an Chen
- Department of Pathology, Guangyuan Central Hospital, Guangyuan, Sichuan, China
| | - Zhengdong Li
- Precision Medical Centre, Guangyuan Central Hospital, Guangyuan, Sichuan, China
| | - Junzhu Chen
- Department of Pathology, Guangyuan Central Hospital, Guangyuan, Sichuan, China
| | - Zhe Xu
- Guangyuan Central Hospital, Guangyuan, Sichuan, China
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Wang H, Zhang Y, Miao H, Xu T, Nie X, Cheng W. CircRAD23B promotes proliferation and carboplatin resistance in ovarian cancer cell lines and organoids. Cancer Cell Int 2024; 24:42. [PMID: 38273320 PMCID: PMC10811902 DOI: 10.1186/s12935-024-03228-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Accepted: 01/15/2024] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) are involved in the regulation of progression and drug resistance in ovarian cancer (OC). In the present study, we aimed to explore the role of circRAD23B, a newly identified circRNA, in the regulation of carboplatin-resistant OC. METHODS CircRAD23B expression levels were measured using qRT-PCR. The biological roles of circRAD23B were analysed using CCK-8, colony formation, EDU, flow cytometry, and cell viability assays. RNA pull-down and luciferase assays were used to investigate the interactions of circRAD23B with mRNAs and miRNAs. RESULTS CircRAD23B was significantly increased in carboplatin-resistant OC tissues. CircRAD23B promoted proliferation and reduced sensitivity to carboplatin in cell lines and patient-derived organoids (PDOs), consistent with in vivo findings. Mechanistically, circRAD23B acted as a molecular sponge, abrogating its inhibitory effect on Y-box binding protein 1 (YBX1) by adsorbing miR-1287-5p. Rescue experiments confirmed that the pro-proliferation and carboplatin resistance mediated by circRAD23B was partially reversed by the upregulation of miR-1287-5p. CONCLUSIONS Our results demonstrated, for the first time, the role of the circRAD23B/miR-1287-5p/YBX1 axis in OC progression and carboplatin resistance in cell lines, PDOs, and animal models, providing a basis for the development of targeted therapies for patients with OC.
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Affiliation(s)
- Hui Wang
- Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
| | - Yashuang Zhang
- Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
| | - Huixian Miao
- Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
| | - Ting Xu
- Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
| | - Xianglin Nie
- Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
| | - Wenjun Cheng
- Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
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Li H, Lin R, Zhang Y, Zhu Y, Huang S, Lan J, Lu N, Xie C, He S, Zhang W. N6-methyladenosine-modified circPLPP4 sustains cisplatin resistance in ovarian cancer cells via PIK3R1 upregulation. Mol Cancer 2024; 23:5. [PMID: 38184597 PMCID: PMC10770956 DOI: 10.1186/s12943-023-01917-5] [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: 04/01/2022] [Accepted: 12/15/2023] [Indexed: 01/08/2024] Open
Abstract
BACKGROUND Cisplatin (CDDP) is the first-line chemotherapeutic strategy to treat patients with ovarian cancer (OC). The development of CDDP resistance remains an unsurmountable obstacle in OC treatment and frequently induces tumor recurrence. Circular RNAs (circRNAs) are noncoding RNAs with important functions in cancer progression. Whether circRNAs function in CDDP resistance of OC is unclear. METHODS Platinum-resistant circRNAs were screened via circRNA deep sequencing and examined using in situ hybridization (ISH) in OC. The role of circPLPP4 in CDDP resistance was assessed by clone formation and Annexin V assays in vitro, and by OC patient-derived xenografts and intraperitoneal tumor models in vivo. The mechanism underlying circPLPP4-mediated activation of miR-136/PIK3R1 signaling was examined by luciferase reporter assay, RNA pull-down, RIP, MeRIP and ISH. RESULTS circPLPP4 was remarkably upregulated in platinum resistant OC. circPLPP4 overexpression significantly enhanced, whereas circPLPP4 silencing reduced, OC cell chemoresistance. Mechanistically, circPLPP4 acts as a microRNA sponge to sequester miR-136, thus competitively upregulating PIK3R1 expression and conferring CDDP resistance. The increased circPLPP4 level in CDDP-resistant cells was caused by increased RNA stability, mediated by increased N6-methyladenosine (m6A) modification of circPLPP4. In vivo delivery of an antisense oligonucleotide targeting circPLPP4 significantly enhanced CDDP efficacy in a tumor model. CONCLUSIONS Our study reveals a plausible mechanism by which the m6A -induced circPLPP4/ miR-136/ PIK3R1 axis mediated CDDP resistance in OC, suggesting that circPLPP4 may serve as a promising therapeutic target against CDDP resistant OC. A circPLPP4-targeted drug in combination with CDDP might represent a rational regimen in OC.
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Affiliation(s)
- Han Li
- Department of Gynecology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
| | - Run Lin
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China
| | - Yanna Zhang
- Department of Gynecology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, China
| | - Yanni Zhu
- Department of Gynecology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
| | - Shuting Huang
- Department of Gynecology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
| | - Jing Lan
- Department of Gynecology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
| | - Nian Lu
- Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, China
| | - Chuanmiao Xie
- Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, China.
| | - Shanyang He
- Department of Gynecology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
| | - Weijing Zhang
- Department of Gynecology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, China.
- Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, China.
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Kang Q, Zhang J, Xie C, Fang S, Chai W. Circular RNA SLC8A1 triggers hippocampal neuronal ferroptosis by regulating FUS-mediated ATF3 mRNA stability in epilepsy. Exp Cell Res 2024; 434:113848. [PMID: 37918704 DOI: 10.1016/j.yexcr.2023.113848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 09/27/2023] [Accepted: 10/30/2023] [Indexed: 11/04/2023]
Abstract
BACKGROUND Epilepsy is a neurological disorder characterized by recurrent seizures and is often unresponsive to current treatment options. Ferroptosis, a recently defined iron-dependent regulated cell death, has been suggested as a potential therapeutic target for epilepsy due to its association with oxidative stress. Additionally, circRNA SLC8A1 (circSLC8A1) has been implicated in various neurological disorders and oxidative stress-related diseases but its involvement in epilepsy progression, particularly in relation to ferroptosis and oxidative stress, remains unclear. METHODS qRT-PCR, Western blot, IHC and ELISA assays were employed to validate the relative expression of targeted genes and proteins. The levels of ROS, iron, LOP and GSH were detected by commercial kits. RNA pull-down and RIP assays were employed to detect the interactions among circSLC8A1, FUS and ATF3. A rat epilepsy model was established for further in vivo confirmation. RESULTS AND CONCLUSION In this study, we investigated the potential involvement of circSLC8A1 in epilepsy progression and its connection to ferroptosis and oxidative stress. Our findings demonstrate that circSLC8A1 triggers neuronal ferroptosis by stabilizing ATF3 mRNA expression through recruitment with FUS. The induced neuronal ferroptosis contributes to epilepsy progression. These results enhance our understanding of epilepsy pathogenesis and may provide insights for the development of novel therapeutic strategies.
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Affiliation(s)
- Qin Kang
- Department of Neurology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, Jiangxi Province, PR China
| | - Ji Zhang
- Department of Neurology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, Jiangxi Province, PR China
| | - Chen Xie
- Department of Neurology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, Jiangxi Province, PR China
| | - Susu Fang
- Department of Neurology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, Jiangxi Province, PR China
| | - Wen Chai
- Department of Neurology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, Jiangxi Province, PR China.
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Lin HH, Chang CY, Huang YR, Shen CH, Wu YC, Chang KL, Lee YC, Lin YC, Ting WC, Chien HJ, Zheng YF, Lai CC, Hsiao KY. Exon Junction Complex Mediates the Cap-Independent Translation of Circular RNA. Mol Cancer Res 2023; 21:1220-1233. [PMID: 37527157 DOI: 10.1158/1541-7786.mcr-22-0877] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 06/22/2023] [Accepted: 07/25/2023] [Indexed: 08/03/2023]
Abstract
Evidence that circular RNAs (circRNA) serve as protein template is accumulating. However, how the cap-independent translation is controlled remains largely uncharacterized. Here, we show that the presence of intron and thus splicing promote cap-independent translation. By acquiring the exon junction complex (EJC) after splicing, the interaction between circRNA and ribosomes was promoted, thereby facilitating translation. Prevention of splicing by treatment with spliceosome inhibitor or mutating splicing signal hindered cap-independent translation of circRNA. Moreover, EJC-tethering using Cas13 technology reconstituted EJC-dependent circRNA translation. Finally, the level of a coding circRNA from succinate dehydrogenase assembly factor 2 (circSDHAF2) was found to be elevated in the tumorous tissues from patients with colorectal cancer, and shown to be critical in tumorigenesis of colorectal cancer in both cell and murine models. These findings reveal that EJC-dependent control of circSDHAF2 translation is involved in the regulation of oncogenic pathways. IMPLICATIONS EJC-mediated cap-independent translation of circRNA is implicated in the tumorigenesis of colorectal cancer.
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Affiliation(s)
- Hui-Hsuan Lin
- Doctoral Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung, Taiwan
- Institute of Biochemistry, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan
| | - Chiu-Yuan Chang
- Institute of Biochemistry, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan
| | - Yi-Ren Huang
- Institute of Biochemistry, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan
| | - Che-Hung Shen
- Doctoral Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung, Taiwan
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
| | - Yu-Chen Wu
- Institute of Biochemistry, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan
| | - Kai-Li Chang
- Department of Physiology, National Cheng Kung University, Tainan, Taiwan
| | - Yueh-Chun Lee
- Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Ya-Chi Lin
- Department of Plant Pathology, College of Agriculture and Natural Resources, National Chung Hsing University, Taichung, Taiwan
- Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan
| | - Wen-Chien Ting
- Division of Colorectal Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Han-Ju Chien
- Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan
| | - Yi-Feng Zheng
- Institute of Molecular Biology, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan
| | - Chien-Chen Lai
- Institute of Molecular Biology, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan
| | - Kuei-Yang Hsiao
- Doctoral Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung, Taiwan
- Institute of Biochemistry, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan
- Doctoral Program in Translational Medicine, College of Life Sciences, National Chung Hsing University, Taichung
- Rong Hsing Research Center for Translational Medicine, College of Life Sciences, National Chung Hsing University, Taichung
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10
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Ju Z, Lei M, Xuan L, Luo J, Zhou M, Wang Y, Shen L, Skonieczna M, Ivanov DS, M H Zakaly H, Markovic V, Zhou P, Huang R. P53-response circRNA_0006420 aggravates lung cancer radiotherapy resistance by promoting formation of HUR/PTBP1 complex. J Adv Res 2023:S2090-1232(23)00203-5. [PMID: 37541584 DOI: 10.1016/j.jare.2023.07.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Revised: 07/18/2023] [Accepted: 07/26/2023] [Indexed: 08/06/2023] Open
Abstract
BACKGROUND p53 wild-type lung cancer cells can develop radiation resistance. Circular RNA (circRNA) consists of a family of transcripts with exclusive structures. circRNA is critical in tumorigenesis and is a potential biomarker or therapeutic target. It is uncertain how circRNA expression and functions are regulated post-radiation in p53 wild-type cancer cells. METHODS A549 or H1299 cells were divided into p53-wt and p53-KO groups by CRISPR/Cas9; both groups were subjected to 4Gy ionizing radiation (IR: p53-wt-IR and p53-KO-IR). RNA-seq, CCK8, cell cycle, and other functional and mechanism experiments were performed in vivo. p53 gene knockout mice were generated to test the cell results in vitro. RESULTS circRNAs were found in differential groups. circRNA_0006420 (IRSense) was upregulated in p53-wt cells but had the same expression level as p53-KO cells after radiation, indicating that p53 silencing prevents its upregulation after IR. In the presence of p53, upregulated IRSense post-radiation induces G2/M arrest by regulating DNA damage repair (DDR) pathway-related proteins. Meanwhile, upregulated IRSense post-radiation aggravates the radiation-induced epithelial-mesenchymal transition (EMT). Interestingly, in the presence of p53, it promotes IRSense/HUR/PTBP1 complex formation resulting in the promotion of the radiation-induced EMT. Moreover, c-Jun regulates the upregulation of p53 transcription after radiation treatment. For these lung cancer cells with p53, upregulated IRSense aggravates lung cancer cell proliferation and increases radiation resistance by interacting with HUR (ElAV-like protein 1) and PTBP1 (polypyrimidine tract-binding protein 1) in the nucleus. CONCLUSIONS Lung cancer cells retaining p53 may upregulate circRNA_0006420 (IRSense) expression post radiation to form an IRSense/HUR/PTBP1 complex leading to radiotherapy resistance. This study furthers our understanding of the roles of circRNA in regulating the effect of radiotherapy and provides novel therapeutic avenues for effective clinical lung cancer therapies.
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Affiliation(s)
- Zhao Ju
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, 410078, China
| | - Mingjun Lei
- Department of Oncology, Xiangya Hospital, Central South University.
| | - Lihui Xuan
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, 410078, China.
| | - Jinhua Luo
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, 410078, China.
| | - Meiling Zhou
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, 410078, China.
| | - Yin Wang
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, 410078, China.
| | - Liangfang Shen
- Department of Oncology, Xiangya Hospital, Central South University.
| | - Magdalena Skonieczna
- Department of Systems Biology and Engineering, Silesian University of Technology, Institute of Automatic Control, Akademicka 16, Gliwice 44-100, Poland, Biotechnology Centre, Silesian University of Technology, Krzywoustego 8, Gliwice 44-100, Poland.
| | - Dmitry S Ivanov
- Quantum Electronics Division, Lebedev Physical Institute, 119991 Moscow, Russia.
| | - Hesham M H Zakaly
- Experimental Physics Department, Institute of Physics and Technology, Ural Federal University, Ekaterinburg, Russia.
| | - Vladimir Markovic
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac.
| | - Pingkun Zhou
- Beijing Institute of Radiation medicine, Beijing, China.
| | - Ruixue Huang
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, 410078, China.
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11
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Zhang M, Xu Y, Zhang Y, Lou G. E2F8 knockdown suppresses cell proliferation and induces cell cycle arrest via Wnt/β-Catenin pathway in ovarian cancer. CHINESE J PHYSIOL 2023; 66:266-275. [PMID: 37635486 DOI: 10.4103/cjop.cjop-d-22-00142] [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] [Indexed: 08/29/2023] Open
Abstract
Ovarian cancer is one of the leading causes of death in female reproductive system cancers. However, the pathogenesis of ovarian cancer remains elusive. Our aim is to investigate the potential targets for ovarian cancer. Two microarray datasets were obtained from the Gene Expression Omnibus public database. Using R package limma, the differentially expressed genes (DEGs) were identified from the datasets. There were 95 overlapping DEGs in two microarray datasets. GO, KEGG pathway analysis, and protein-protein interaction (PPI) network analysis were carried out based on the DEGs. Wnt signaling pathway and cell cycle were enriched in the KEGG pathway analysis. Moreover, the top 10 hub genes with the most nodes were determined by PPI network analysis. E2F8, one of hub genes was positively linked to a bad outcome in ovarian cancer patients. Furthermore, E2F8 knockdown suppressed cell proliferation and induced cell cycle arrest in ovarian cancer. In addition, we found that silencing E2F8 inhibited the Wnt/β-catenin signaling pathway. In ovarian cancer cells with E2F8 knockdown, overexpressing β-catenin restored both the suppressed capacity of cell proliferation and cell cycle progression. Therefore, our results revealed that E2F8 had an involvement in the development of ovarian cancer which might act as a therapeutic target.
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Affiliation(s)
- Meiyin Zhang
- Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Ye Xu
- Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Yongjian Zhang
- Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Ge Lou
- Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
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12
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Tong Y, Zhang S, Riddle S, Song R, Yue D. Circular RNAs in the Origin of Developmental Lung Disease: Promising Diagnostic and Therapeutic Biomarkers. Biomolecules 2023; 13:biom13030533. [PMID: 36979468 PMCID: PMC10046088 DOI: 10.3390/biom13030533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 03/11/2023] [Accepted: 03/12/2023] [Indexed: 03/17/2023] Open
Abstract
Circular RNA (circRNA) is a newly discovered noncoding RNA that regulates gene transcription, binds to RNA-related proteins, and encodes protein microRNAs (miRNAs). The development of molecular biomarkers such as circRNAs holds great promise in the diagnosis and prognosis of clinical disorders. Importantly, circRNA-mediated maternal-fetus risk factors including environmental (high altitude), maternal (preeclampsia, smoking, and chorioamnionitis), placental, and fetal (preterm birth and low birth weight) factors are the early origins and likely to contribute to the occurrence and progression of developmental and pediatric cardiopulmonary disorders. Although studies of circRNAs in normal cardiopulmonary development and developmental diseases have just begun, some studies have revealed their expression patterns. Here, we provide an overview of circRNAs’ biogenesis and biological functions. Furthermore, this review aims to emphasize the importance of circRNAs in maternal-fetus risk factors. Likewise, the potential biomarker and therapeutic target of circRNAs in developmental and pediatric lung diseases are explored.
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Affiliation(s)
- Yajie Tong
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Shuqing Zhang
- School of Pharmacy, China Medical University, Shenyang 110122, China
| | - Suzette Riddle
- Cardiovascular Pulmonary Research Laboratories, Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Rui Song
- Lawrence D. Longo MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA
- Correspondence: (R.S.); (D.Y.); Tel.: +01-909-558-4325 (R.S.); +86-24-9661551125 (D.Y.)
| | - Dongmei Yue
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Correspondence: (R.S.); (D.Y.); Tel.: +01-909-558-4325 (R.S.); +86-24-9661551125 (D.Y.)
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13
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Liu M, Cao S, Guo Z, Wu Z, Meng J, Wu Y, Shao Y, Li Y. Roles and mechanisms of CircRNAs in ovarian cancer. Front Cell Dev Biol 2022; 10:1044897. [PMID: 36506086 PMCID: PMC9727202 DOI: 10.3389/fcell.2022.1044897] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 11/09/2022] [Indexed: 11/24/2022] Open
Abstract
Ovarian cancer (OC) is one of the female malignancies with nearly 45% 5-year survival rate. Circular RNAs (circRNAs), a kind of single-stranded non-coding RNAs, are generated from the back-splicing of cellular housekeeping noncoding RNAs and precursor messenger RNAs. Recent studies revealed that circRNAs have different biological function, including sponging miRNAs, encoding micropeptides, regulating stability of cytoplasmic mRNAs, affecting transcription and splicing, via interacting with DNA, RNA and proteins. Due to their stability, circRNAs have the potential of acting as biomarkers and treatment targets. In this review, we briefly illustrate the biogenesis mechanism and biological function of circRNAs in OC, and make a perspective of circRNAs drug targeting immune responses and signaling pathways in OC. This article can provide a systematic view into the current situation and future of circRNAs in OC.
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Affiliation(s)
- Min Liu
- Lab for Noncoding RNA and Cancer, School of Life Sciences, Shanghai University, Shanghai, China
| | - Siyu Cao
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Ziyi Guo
- Lab for Noncoding RNA and Cancer, School of Life Sciences, Shanghai University, Shanghai, China
| | - Zong Wu
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiao Meng
- Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yong Wu
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yang Shao
- Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yanli Li
- Lab for Noncoding RNA and Cancer, School of Life Sciences, Shanghai University, Shanghai, China
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Circular RNAs in Epithelial Ovarian Cancer: From Biomarkers to Therapeutic Targets. Cancers (Basel) 2022; 14:cancers14225711. [PMID: 36428803 PMCID: PMC9688053 DOI: 10.3390/cancers14225711] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/15/2022] [Accepted: 11/16/2022] [Indexed: 11/24/2022] Open
Abstract
Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, and more than 70% of patients are diagnosed at advanced stages. Despite the application of surgery and chemotherapy, the prognosis remains poor due to the high relapse rate. It is urgent to identify novel biomarkers and develop novel therapeutic strategies for EOC. Circular RNAs (circRNAs) are a class of noncoding RNAs generated from the "back-splicing" of precursor mRNA. CircRNAs exert their functions via several mechanisms, including acting as miRNA sponges, interacting with proteins, regulating transcription, and encoding functional proteins. Recent studies have identified many circRNAs that are dysregulated in EOC and may be used as diagnostic and prognostic markers. Increasing evidence has revealed that circRNAs play a critical role in ovarian cancer progression by regulating various cellular processes, including proliferation, apoptosis, metastasis, and chemosensitivity. The circRNA-based therapy may be a novel strategy that is worth exploring in the future. Here, we provide an overview of EOC and circRNA biogenesis and functions. We then discuss the dysregulations of circRNAs in EOC and the possibility of using them as diagnostic/prognostic markers. We also summarize the role of circRNAs in regulating ovarian cancer development and speculate their potential as therapeutic targets.
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15
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Xing Y, Liang X, Lv X, Cheng Y, Du J, Liu C, Yang Y. New insights into the role of circular RNAs in ovarian cancer. Pathol Res Pract 2022; 238:154073. [PMID: 36007396 DOI: 10.1016/j.prp.2022.154073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 07/31/2022] [Accepted: 08/10/2022] [Indexed: 10/15/2022]
Abstract
Ovarian cancer (OC) is one of the most aggressive tumors in women and has a poor prognosis and the highest mortality rate. Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs that have recently attracted interest in cancer research. Increasing evidence has demonstrated that circRNAs play an oncogenic or suppressive role in tumorigenesis and progression, and show tissue- or developmental-stage-specific expression. Due to high stability, conservation, abundance, and specificity, circRNAs are considered promising biomarkers for the diagnosis and prognosis of cancer. Herein, we have summarized the expression profiles of circRNAs in OC tissues, serums, and cell lines. Moreover, we discuss how circRNAs participate in the regulation of multiple biological processes in OC, including cell proliferation, apoptosis, migration, invasion, autophagy, epithelial-to-mesenchymal transition, glucose metabolism, angiogenesis, immune response, and chemotherapy resistance, by sponging microRNAs and interacting with proteins.
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Affiliation(s)
- Yijuan Xing
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000 Gansu, China; Department of Obstetrics and Gynecology, First Hospital of Lanzhou University, Key Laboratory of Gynecologic Oncology Gansu Province, Lanzhou 730000, Gansu, China
| | - Xiaolei Liang
- Department of Obstetrics and Gynecology, First Hospital of Lanzhou University, Key Laboratory of Gynecologic Oncology Gansu Province, Lanzhou 730000, Gansu, China; Department of Obstetrics and Gynecology, First Hospital of Lanzhou University, Lanzhou 730000 Gansu, China
| | - Xiao Lv
- Department of Obstetrics and Gynecology, First Hospital of Lanzhou University, Key Laboratory of Gynecologic Oncology Gansu Province, Lanzhou 730000, Gansu, China; Department of Obstetrics and Gynecology, First Hospital of Lanzhou University, Lanzhou 730000 Gansu, China
| | - Yuemei Cheng
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000 Gansu, China; Department of Obstetrics and Gynecology, First Hospital of Lanzhou University, Key Laboratory of Gynecologic Oncology Gansu Province, Lanzhou 730000, Gansu, China
| | - Junhong Du
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000 Gansu, China; Department of Obstetrics and Gynecology, First Hospital of Lanzhou University, Key Laboratory of Gynecologic Oncology Gansu Province, Lanzhou 730000, Gansu, China
| | - Chang Liu
- Department of Obstetrics and Gynecology, First Hospital of Lanzhou University, Key Laboratory of Gynecologic Oncology Gansu Province, Lanzhou 730000, Gansu, China; Department of Obstetrics and Gynecology, First Hospital of Lanzhou University, Lanzhou 730000 Gansu, China
| | - Yongxiu Yang
- Department of Obstetrics and Gynecology, First Hospital of Lanzhou University, Key Laboratory of Gynecologic Oncology Gansu Province, Lanzhou 730000, Gansu, China; Department of Obstetrics and Gynecology, First Hospital of Lanzhou University, Lanzhou 730000 Gansu, China.
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16
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Najafi S. The emerging roles and potential applications of circular RNAs in ovarian cancer: a comprehensive review. J Cancer Res Clin Oncol 2022; 149:2211-2234. [PMID: 36053324 DOI: 10.1007/s00432-022-04328-z] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 08/24/2022] [Indexed: 12/25/2022]
Abstract
Ovarian cancer (OC) is among the most common human malignancies and the first cause of deaths among gynecologic cancers. Early diagnosis can help improving prognosis in those patients, and accordingly exploring novel molecular mechanisms may lead to find therapeutic targets. Circular RNAs (circRNAs) comprise a group of non-coding RNAs in multicellular organisms, which are identified with characteristic circular structure. CircRNAs have been found with substantial functions in regulating gene expression through interacting with RNA-binding proteins, targeting microRNAs, and transcriptional regulation. They have been found to be involved in regulating several critical processes such as cell growth, and death, organ development, signal transduction, and tumorigenesis. Accordingly, circRNAs have been implicated in a number of human diseases including malignancies. They are particularly reported to contribute to several hallmarks of cancer leading to cancer development and progression, although a number also are described with tumor-suppressor function. In OC, circRNAs are linked to regulation of cell growth, invasiveness, metastasis, angiogenesis, and chemoresistance. Notably, clinical studies also have shown potentials in diagnosis, prediction of prognosis, and therapeutic targets for OC. In this review, I have an overview to the putative mechanisms, and functions of circRNAs in regulating OC pathogenesis in addition to their clinical potentials.
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Affiliation(s)
- Sajad Najafi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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17
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Ran Y, Chen R, Huang D, Qin Y, Liu Z, He J, Mei Y, Zhou Y, Yin N, Qi H. The landscape of circular RNA in preterm birth. Front Immunol 2022; 13:879487. [PMID: 36072601 PMCID: PMC9441874 DOI: 10.3389/fimmu.2022.879487] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Accepted: 08/03/2022] [Indexed: 12/24/2022] Open
Abstract
Background Preterm birth (PTB) is a multifactorial syndrome that seriously threatens the health of pregnant women and babies worldwide. Recently, circular RNAs (circRNAs) have been understood as important regulators of various physiological and pathological processes. However, the expression pattern and potential roles of circRNAs in PTB are largely unclear. Methods In this study, we extracted and analyzed the circRNA expression profiles in maternal and fetal samples of preterm and term pregnancies, including maternal plasma, maternal monocytes, myometrium, chorion, placenta, and cord blood. We identified the circRNAs which is associated with PTB in different tissues and explored their relationships from the perspective of the overall maternal-fetal system. Furthermore, co-expression analysis of circRNAs and mRNAs, target microRNAs (miRNAs), and RNA-binding proteins (RBPs), provided new clues about possible mechanisms of circRNA function in PTB. In the end, we investigated the potential special biofunctions of circRNAs in different tissues and their common features and communication in PTB. Results Significant differences in circRNA types and expression levels between preterm and term groups have been proved, as well as between tissues. Nevertheless, there were still some PTB-related differentially expressed circRNAs (DECs) shared by these tissues. The functional enrichment analysis showed that the DECs putatively have important tissue-specific biofunctions through their target miRNA and co-expressed mRNAs, which contribute to the signature pathologic changes of each tissue within the maternal-fetal system in PTB (e.g., the contraction of the myometrium). Moreover, DECs in different tissues might have some common biological activities, which are mainly the activation of immune-inflammatory processes (e.g., interleukin1/6/8/17, chemokine, TLRs, and complement). Conclusions In summary, our data provide a preliminary blueprint for the expression and possible roles of circRNAs in PTB, which lays the foundation for future research on the mechanisms of circRNAs in PTB.
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Affiliation(s)
- Yuxin Ran
- Women and Children’s Hospital of Chongqing Medical University (Chongqing Health Center for Women and Children), Chongqing, China
- Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
- Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Ruixin Chen
- Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, China
| | - Dongni Huang
- Women and Children’s Hospital of Chongqing Medical University (Chongqing Health Center for Women and Children), Chongqing, China
- Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
| | - Yan Qin
- Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zheng Liu
- Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
- Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jie He
- Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
- Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Youwen Mei
- Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
- Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yunqian Zhou
- Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
- Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Nanlin Yin
- Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
- Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
- Center for Reproductive Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- *Correspondence: Nanlin Yin, ; Hongbo Qi,
| | - Hongbo Qi
- Women and Children’s Hospital of Chongqing Medical University (Chongqing Health Center for Women and Children), Chongqing, China
- Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
- *Correspondence: Nanlin Yin, ; Hongbo Qi,
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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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Ghafouri-Fard S, Khoshbakht T, Hussen BM, Taheri M, Samsami M. Emerging role of circular RNAs in the pathogenesis of ovarian cancer. Cancer Cell Int 2022; 22:172. [PMID: 35488239 PMCID: PMC9052556 DOI: 10.1186/s12935-022-02602-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 04/18/2022] [Indexed: 01/11/2023] Open
Abstract
Ovarian cancer is a female malignancy with high fatality-to-case ratio, which is due to late detection of cancer. Understanding the molecular mechanisms participating in these processes would facilitate design of therapeutic modalities and identification of novel tumor markers. Recent investigations have shown contribution of circular RNAs (circRNAs) in the evolution of ovarian cancer. These transcripts are produced through a back-splicing mechanism. The enclosed configuration of circRNAs protects them from degradation and potentiates them as biomarkers. Several circRNAs such as circMUC16, circRNA_MYLK, circRNA-UBAP2, circWHSC1, hsa_circ_0013958, circFGFR3, hsa_circRNA_102958 and circ_0072995 have been found to be up-regulated in this cancer, acting as oncogenes. On the other hand, circ-ITCH, circPLEKHM3, circ_100395, circ_0078607, circATRNL1, circHIPK3, circRHOBTB3, circEXOC6B, circ9119 and CDR1as are among down-regulated circRNAs in ovarian cancer. Expression levels of circCELSR1, circ_CELSR1, circATL2, circNRIP1, circTNPO3 and hsa_circ_0000714 have been shown to affect resistance of ovarian cancer cells to chemotherapy. Moreover, circ_100395, circFGFR3, circ_0000554, circCELSR1, circ-PTK2, circLNPEP, circ-CSPP1, circ_0000745, circ_100395 and circPLEKHM3 have been shown to regulate epithelial-mesenchymal transition and metastatic ability of ovarian cancer cells. In the current review, we explain the roles of circRNAs in the evolution and progression of ovarian cancer.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tayyebeh Khoshbakht
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bashdar Mahmud Hussen
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Arbīl, Kurdistan Region, Iraq
- Center of Research and Strategic Studies, Lebanese French University, Arbīl, Kurdistan Region, Iraq
| | - Mohammad Taheri
- Institute of Human Genetics, Jena University Hospital, Jena, Germany.
| | - Majid Samsami
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Lyu M, Li X, Shen Y, Lu J, Zhang L, Zhong S, Wang J. CircATRNL1 and circZNF608 Inhibit Ovarian Cancer by Sequestering miR-152-5p and Encoding Protein. Front Genet 2022; 13:784089. [PMID: 35281849 PMCID: PMC8905624 DOI: 10.3389/fgene.2022.784089] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 01/31/2022] [Indexed: 12/27/2022] Open
Abstract
Background: CircRNAs have been found to be involved in the pathogenesis of various diseases. We aimed to explore the roles of circRNAs in ovarian cancer. Methods: The expression levels of circRNAs in ovarian cancer and normal ovarian tissues were analyzed using RNA sequencing. Fluorescent in situ hybridization (FISH), proliferation assays and transwell assays were used to assess the effects of circRNAs on ovarian cancer. Results: CircATRNL1 and circZNF608 were downregulated in 20 ovarian cancer tissues compared to normal tissues. CircATRNL1 and circZNF608 are mainly located in the cytoplasm of ovarian cancer cells, and circATRNL1 is a highly conserved circRNA. The overexpression of circATRNL1 and circZNF608 inhibits the proliferation and invasion of ovarian cancer cells. We predicted miRNA–circRNA interactions for circZNF608 and circATRNL1 and obtained 63 interactions. However, a luciferase reporter assay showed that only miR-152-5p was sequestered by circZNF608. Bioinformatics analysis and experiments indicated that circATRNL1 contains an internal ribosome entry site and an open reading frame encoding a 131 aa protein. Conclusion: In conclusion, circATRNL1 and circZNF608 are two downregulated circRNAs in ovarian cancer and work as tumor suppressors. CircZNF608 may exert antitumor activity in ovarian cancer by binding miR-152-5p, and circATRNL1 may encode a 131 aa protein.
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Affiliation(s)
- Mengmeng Lyu
- Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, China
| | - Xiujuan Li
- Department of General Surgery, The Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, China
| | - Yang Shen
- Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, China
| | - Jin Lu
- Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, China
| | - Lihua Zhang
- Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, China
| | - Shanliang Zhong
- Center of Clinical Laboratory Science, The Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, China
| | - Jinhua Wang
- Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, China
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21
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Wu J, Wu Y, Guo Q, Wang S, Wu X. RNA-binding proteins in ovarian cancer: a novel avenue of their roles in diagnosis and treatment. J Transl Med 2022; 20:37. [PMID: 35062979 PMCID: PMC8783520 DOI: 10.1186/s12967-022-03245-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 01/11/2022] [Indexed: 12/18/2022] Open
Abstract
Ovarian cancer (OC), an important cause of cancer-related death in women worldwide, is one of the most malignant cancers and is characterized by a poor prognosis. RNA-binding proteins (RBPs), a class of endogenous proteins that can bind to mRNAs and modify (or even determine) the amount of protein they can generate, have attracted great attention in the context of various diseases, especially cancers. Compelling studies have suggested that RBPs are aberrantly expressed in different cancer tissues and cell types, including OC tissues and cells. More specifically, RBPs can regulate proliferation, apoptosis, invasion, metastasis, tumorigenesis and chemosensitivity and serve as potential therapeutic targets in OC. Herein, we summarize what is currently known about the biogenesis, molecular functions and potential roles of human RBPs in OC and their prospects for application in the clinical treatment of OC.
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Affiliation(s)
- Jiangchun Wu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.,Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People's Republic of China
| | - Yong Wu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.,Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People's Republic of China
| | - Qinhao Guo
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.,Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People's Republic of China
| | - Simin Wang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.,Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People's Republic of China
| | - Xiaohua Wu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. .,Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People's Republic of China.
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22
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Shi Y, Liu JB, Deng J, Zou DZ, Wu JJ, Cao YH, Yin J, Ma YS, Da F, Li W. The role of ceRNA-mediated diagnosis and therapy in hepatocellular carcinoma. Hereditas 2021; 158:44. [PMID: 34758879 PMCID: PMC8582193 DOI: 10.1186/s41065-021-00208-7] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 10/12/2021] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide due to its high degree of malignancy, high incidence, and low survival rate. However, the underlying mechanisms of hepatocarcinogenesis remain unclear. Long non coding RNA (lncRNA) has been shown as a novel type of RNA. lncRNA by acting as ceRNA can participate in various biological processes of HCC cells, such as tumor cell proliferation, migration, invasion, apoptosis and drug resistance by regulating downstream target gene expression and cancer-related signaling pathways. Meanwhile, lncRNA can predict the efficacy of treatment strategies for HCC and serve as a potential target for the diagnosis and treatment of HCC. Therefore, lncRNA serving as ceRNA may become a vital candidate biomarker for clinical diagnosis and treatment. In this review, the epidemiology of HCC, including morbidity, mortality, regional distribution, risk factors, and current treatment advances, was briefly discussed, and some biological functions of lncRNA in HCC were summarized with emphasis on the molecular mechanism and clinical application of lncRNA-mediated ceRNA regulatory network in HCC. This paper can contribute to the better understanding of the mechanism of the influence of lncRNA-mediated ceRNA networks (ceRNETs) on HCC and provide directions and strategies for future studies.
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Affiliation(s)
- Yi Shi
- College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou, 412007, Hunan, China.,Cancer Institute, Affiliated Tumor Hospital of Nantong University, Nantong, 226631, China.,National Engineering Laboratory for Deep Process of Rice and Byproducts, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, 410004, Hunan, China
| | - Ji-Bin Liu
- Cancer Institute, Affiliated Tumor Hospital of Nantong University, Nantong, 226631, China
| | - Jing Deng
- National Engineering Laboratory for Deep Process of Rice and Byproducts, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, 410004, Hunan, China
| | - Da-Zhi Zou
- Department of Spine Surgery, Longhui County People's Hospital, Longhui, 422200, Hunan, China
| | - Jian-Jun Wu
- Nantong Haimen Yuelai Health Centre, Haimen, 226100, China
| | - Ya-Hong Cao
- Department of Respiratory, Nantong Traditional Chinese Medicine Hospital, Nantong, 226019, Jiangsu Province, China
| | - Jie Yin
- Department of General Surgery, Haian people's Hospital, Haian, 226600, Jiangsu, China
| | - Yu-Shui Ma
- Cancer Institute, Affiliated Tumor Hospital of Nantong University, Nantong, 226631, China.
| | - Fu Da
- Cancer Institute, Affiliated Tumor Hospital of Nantong University, Nantong, 226631, China. .,National Engineering Laboratory for Deep Process of Rice and Byproducts, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, 410004, Hunan, China.
| | - Wen Li
- College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou, 412007, Hunan, China. .,National Engineering Laboratory for Deep Process of Rice and Byproducts, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, 410004, Hunan, China.
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Das A, Sinha T, Shyamal S, Panda AC. Emerging Role of Circular RNA-Protein Interactions. Noncoding RNA 2021; 7:48. [PMID: 34449657 PMCID: PMC8395946 DOI: 10.3390/ncrna7030048] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 07/26/2021] [Accepted: 07/29/2021] [Indexed: 12/17/2022] Open
Abstract
Circular RNAs (circRNAs) are emerging as novel regulators of gene expression in various biological processes. CircRNAs regulate gene expression by interacting with cellular regulators such as microRNAs and RNA binding proteins (RBPs) to regulate downstream gene expression. The accumulation of high-throughput RNA-protein interaction data revealed the interaction of RBPs with the coding and noncoding RNAs, including recently discovered circRNAs. RBPs are a large family of proteins known to play a critical role in gene expression by modulating RNA splicing, nuclear export, mRNA stability, localization, and translation. However, the interaction of RBPs with circRNAs and their implications on circRNA biogenesis and function has been emerging in the last few years. Recent studies suggest that circRNA interaction with target proteins modulates the interaction of the protein with downstream target mRNAs or proteins. This review outlines the emerging mechanisms of circRNA-protein interactions and their functional role in cell physiology.
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Affiliation(s)
- Arundhati Das
- Institute of Life Sciences, Nalco Square, Bhubaneswar 751023, India; (A.D.); (T.S.); (S.S.)
- School of Biotechnology, KIIT University, Bhubaneswar 751024, India
| | - Tanvi Sinha
- Institute of Life Sciences, Nalco Square, Bhubaneswar 751023, India; (A.D.); (T.S.); (S.S.)
| | - Sharmishtha Shyamal
- Institute of Life Sciences, Nalco Square, Bhubaneswar 751023, India; (A.D.); (T.S.); (S.S.)
| | - Amaresh Chandra Panda
- Institute of Life Sciences, Nalco Square, Bhubaneswar 751023, India; (A.D.); (T.S.); (S.S.)
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