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1
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Sheng S, Guo J, Lu C, Hu X. Non-coding RNAs in thoracic disease: Barrett's esophagus and esophageal adenocarcinoma. Clin Chim Acta 2025; 571:120242. [PMID: 40074193 DOI: 10.1016/j.cca.2025.120242] [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: 01/31/2025] [Revised: 03/08/2025] [Accepted: 03/09/2025] [Indexed: 03/14/2025]
Abstract
Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy with increasing incidence and poor survival rates, primarily due to late-stage diagnosis. This cancer often develops from Barrett's Esophagus (BE), a precancerous condition linked to chronic gastroesophageal reflux disease (GERD). The transition from BE to EAC is a complex multistep process involving numerous genetic, epigenetic, and molecular changes that lead to the malignant transformation of the esophageal epithelium. Despite advancements in understanding the molecular mechanisms underlying EAC, early detection and effective treatment options remain limited, highlighting an urgent need for innovative diagnostic and therapeutic strategies. Recent research has focused on non-coding RNAs (ncRNAs), which play crucial roles in regulating gene expression and cellular processes relevant to cancer progression. Various types of ncRNAs, including microRNAs, long non-coding RNAs, and circular RNAs, have been implicated in the development of BE and EAC by modulating key signaling pathways such as Wnt/β-catenin and NF-κB. Additionally, ncRNAs are stable in biological fluids, presenting opportunities for their use as non-invasive biomarkers for early detection and monitoring of EAC. This review aims to elucidate the involvement of ncRNAs in the progression from BE to EAC, their potential as therapeutic targets, and their emerging roles in intercellular communication. We will also discuss the challenges in translating ncRNA research into clinical applications, emphasizing their promise in revolutionizing early detection and treatment strategies for EAC.
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Affiliation(s)
- Siyuan Sheng
- Department of Medicine, Hunan University of Arts and Science, Changde, Hunan Province 415000, China.
| | - Jianhui Guo
- Spine Surgery of Changde Second People's Hospital, Changde, Hunan Province 415000, China
| | - Chuangang Lu
- Sanya Central Hospital, Sanya, Hainan Province 572000, China
| | - Xia Hu
- Department of Medicine, Hunan University of Arts and Science, Changde, Hunan Province 415000, China
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2
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Guo X, Huang A, Qi Y, Chen J, Yang M, Jin M. METTL3/IGF2BP2 Promotes the Malignant Progression of Esophageal Cancer by Activating the PIK3CA/AKT Pathway. Thorac Cancer 2025; 16:e70022. [PMID: 39980152 PMCID: PMC11842509 DOI: 10.1111/1759-7714.70022] [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: 12/02/2024] [Revised: 01/23/2025] [Accepted: 02/10/2025] [Indexed: 02/22/2025] Open
Abstract
Esophageal cancer (EC) is a leading cause of cancer-related mortality worldwide. Methyltransferase-like 3 (METTL3), a key enzyme involved in m6A methylation, has been implicated in the development and progression of various cancers, including EC. However, its potential mechanism of action in EC progression remains unclear. METTL3 expression was found to be upregulated in EC tissues and cells. Knockdown of METTL3 suppressed EC cell proliferation, invasion, migration, and angiogenesis, while promoting apoptosis. Mechanistically, METTL3 maintained PIK3CA mRNA expression and stability in an m6A-dependent and IGF2BP2-dependent manner, respectively. METTL3 silencing inactivated the AKT pathway by regulating PIK3CA expression. Furthermore, overexpression of PIK3CA mitigated the effects of METTL3 silencing on the malignant growth of KYSE180 and TE1 cells in vivo and in vitro. METTL3/IGF2BP2 promoted the malignant progression of EC by activating the PIK3CA/AKT pathway. Targeting the METTL3-PIK3CA axis may offer a novel therapeutic approach for EC treatment.
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Affiliation(s)
- Xinmeng Guo
- Department of PathologyBeijing Chao‐Yang Hospital, Capital Medical UniversityBeijingChina
| | - Anqi Huang
- Department of PathologyBeijing Chao‐Yang Hospital, Capital Medical UniversityBeijingChina
| | - Ya'nan Qi
- Department of PathologyBeijing Chao‐Yang Hospital, Capital Medical UniversityBeijingChina
| | - Jiaqi Chen
- Department of PathologyBeijing Chao‐Yang Hospital, Capital Medical UniversityBeijingChina
| | - Meng Yang
- Department of PathologyBeijing Chao‐Yang Hospital, Capital Medical UniversityBeijingChina
| | - Mulan Jin
- Department of PathologyBeijing Chao‐Yang Hospital, Capital Medical UniversityBeijingChina
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3
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Heidarzadehpilehrood R, Pirhoushiaran M. Biomarker potential of competing endogenous RNA networks in Polycystic Ovary Syndrome (PCOS). Noncoding RNA Res 2024; 9:624-640. [PMID: 38571815 PMCID: PMC10988127 DOI: 10.1016/j.ncrna.2024.01.002] [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: 10/22/2023] [Revised: 12/21/2023] [Accepted: 01/08/2024] [Indexed: 04/05/2024] Open
Abstract
Polycystic ovary syndrome (PCOS) is the most common condition affecting women of reproductive age globally. PCOS continues to be the largest contributing factor to female infertility despite significant progress in our knowledge of the molecular underpinnings and treatment of the condition. The fact that PCOS is a very diverse condition makes it one of the key reasons why we haven't been able to overcome it. Non-coding RNAs (ncRNAs) are implicated in the development of PCOS, according to growing evidence. However, it is unclear how the complex regulatory relationships between the many ncRNA types contribute to the growth of this malignancy. Competing endogenous RNA (ceRNA), a recently identified mechanism in the RNA world, suggests regulatory interactions between various RNAs, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), transcribed pseudogenes, and circular RNAs (circRNAs). Recent studies on PCOS have shown that dysregulation of multiple ceRNA networks (ceRNETs) between these ncRNAs plays crucial roles in developing the defining characteristics of PCOS development. And it is believed that such a finding may open a new door for a deeper comprehension of PCOS's unexplored facets. In addition, it may be able to provide fresh biomarkers and effective therapy targets for PCOS. This review will go over the body of information that exists about the primary roles of ceRNETs before highlighting the developing involvement of several newly found ceRNETs in a number of PCOS characteristics.
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Affiliation(s)
- Roozbeh Heidarzadehpilehrood
- Department of Obstetrics & Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia
| | - Maryam Pirhoushiaran
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, 1417613151, Iran
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Ashrafizadeh M, Dai J, Torabian P, Nabavi N, Aref AR, Aljabali AAA, Tambuwala M, Zhu M. Circular RNAs in EMT-driven metastasis regulation: modulation of cancer cell plasticity, tumorigenesis and therapy resistance. Cell Mol Life Sci 2024; 81:214. [PMID: 38733529 PMCID: PMC11088560 DOI: 10.1007/s00018-024-05236-w] [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: 12/05/2023] [Revised: 03/05/2024] [Accepted: 04/03/2024] [Indexed: 05/13/2024]
Abstract
The non-coding RNAs comprise a large part of human genome lack of capacity in encoding functional proteins. Among various members of non-coding RNAs, the circular RNAs (circRNAs) have been of importance in the pathogenesis of human diseases, especially cancer. The circRNAs have a unique closed loop structure and due to their stability, they are potential diagnostic and prognostic factors in cancer. The increasing evidences have highlighted the role of circRNAs in the modulation of proliferation and metastasis of cancer cells. On the other hand, metastasis has been responsible for up to 90% of cancer-related deaths in patients, requiring more investigation regarding the underlying mechanisms modulating this mechanism. EMT enhances metastasis and invasion of tumor cells, and can trigger resistance to therapy. The cells demonstrate dynamic changes during EMT including transformation from epithelial phenotype into mesenchymal phenotype and increase in N-cadherin and vimentin levels. The process of EMT is reversible and its reprogramming can disrupt the progression of tumor cells. The aim of current review is to understanding the interaction of circRNAs and EMT in human cancers and such interaction is beyond the regulation of cancer metastasis and can affect the response of tumor cells to chemotherapy and radiotherapy. The onco-suppressor circRNAs inhibit EMT, while the tumor-promoting circRNAs mediate EMT for acceleration of carcinogenesis. Moreover, the EMT-inducing transcription factors can be controlled by circRNAs in different human tumors.
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Affiliation(s)
- Milad Ashrafizadeh
- Department of Radiation Oncology, Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong 250000, China
- Department of General Surgery and Integrated Chinese and Western Medicine, Institute of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong, 518060, China
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Jingyuan Dai
- School of computer science and information systems, Northwest Missouri State University, Maryville, MO, 64468, USA.
| | - Pedram Torabian
- Cumming School of Medicine, Arnie Charbonneau Cancer Research Institute, University of Calgary, Calgary, AB, T2N 4Z6, Canada
- Department of Medical Sciences, University of Calgary, Calgary, AB, T2N 4Z6, Canada
| | - Noushin Nabavi
- Department of Urologic Sciences and Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, V6H3Z6, Canada
| | - Amir Reza Aref
- Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
- Department of Translational Sciences, Xsphera Biosciences Inc. Boston, Boston, MA, USA
| | - Alaa A A Aljabali
- Faculty of Pharmacy, Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University, Irbid, Jordan
| | - Murtaza Tambuwala
- Lincoln Medical School, University of Lincoln, Brayford Pool Campus, Lincoln, LN6 7TS, UK.
- College of Pharmacy, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates.
| | - Minglin Zhu
- Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
- Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan, Hubei, 430071, China.
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Chu A, Sun C, Liu Z, Liu S, Li M, Song R, Gan L, Wang Y, Fan R. Circ-POSTN promotes the progression and reduces radiosensitivity in esophageal cancer by regulating the miR-876-5p/FYN axis. Thorac Cancer 2024; 15:1082-1094. [PMID: 38553795 PMCID: PMC11062886 DOI: 10.1111/1759-7714.15273] [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: 01/05/2024] [Revised: 02/19/2024] [Accepted: 02/22/2024] [Indexed: 05/03/2024] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) play critical roles in the tumorigenesis and radiosensitivity of multiple cancers. Nevertheless, the biological functions of circRNA periostin (circ-POSTN) in esophageal cancer (EC) progression and radiosensitivity have not been well elucidated. METHODS The expression of circ-POSTN, microRNA-876-5p (miR-876-5p), and proto-oncogene tyrosine-protein kinase (FYN) was analyzed by quantitative reverse transcription PCR (RT-qPCR). Cell proliferation was assessed by MTT, colony formation, and 5-ethynyl-2'-deoxyuridine (EDU) assays. All protein levels were detected by western blot assay. Cell apoptosis and invasion were assessed by flow cytometry analysis and transwell assay, respectively. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction between miR-876-5p and circ-POSTN or FYN. The role of circ-POSTN in vivo was explored by establishing mice xenograft model. RESULTS Circ-POSTN was overexpressed in EC tissues and cells. Knockdown of circ-POSTN inhibited cell proliferation and invasion and elevated apoptosis and radiosensitivity in EC cells. MiR-876-5p was a direct target of circ-POSTN, and its knockdown reversed the role of sh-circ-POSTN in EC cells. FYN was a direct target of miR-876-5p, and FYN elevation weakened the effects of miR-876-5p overexpression on the progression and radiosensitivity of EC cells. Moreover, circ-POSTN acted as a miR-876-5p sponge to regulate FYN expression. Circ-POSTN interference also suppressed tumor growth and enhanced radiosensitivity in vivo. CONCLUSION Circ-POSTN knockdown inhibited proliferation and invasion, but increased apoptosis and enhanced radiosensitivity in EC cells via modulating miR-876-5p/FYN axis, which might be a potential diagnostic and therapeutic target for EC.
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Affiliation(s)
- Alan Chu
- Department of Radiation OncologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Chen Sun
- Department of Radiation OncologyThe Second Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Zongwen Liu
- Department of Radiation OncologyThe Second Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Shijia Liu
- Department of Radiation OncologyThe Second Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Mengxi Li
- Department of Radiation OncologyThe Second Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Rui Song
- Department of Radiation OncologyThe Second Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Lanlan Gan
- Department of Radiation OncologyThe Second Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Yongtai Wang
- Department of Radiation OncologyThe Second Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Ruitai Fan
- Department of Radiation OncologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
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Cui H, Liang X, Zhu Y, Elayah SA, Qi H, Xie L, Guo Z, Siya F, Ming Y, Yuxin G, Tu J, Na S. Mena as a key enhancer factor of EMT to promote metastasis of human tongue squamous cell carcinoma. Oral Dis 2024; 30:2084-2096. [PMID: 37203597 DOI: 10.1111/odi.14616] [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: 03/14/2023] [Revised: 04/08/2023] [Accepted: 05/02/2023] [Indexed: 05/20/2023]
Abstract
OBJECTIVE The aim of this study was to investigate the effect of mammalian-enabled (Mena) on tongue squamous cell carcinoma (TSCC) metastasis and its mechanism. MATERIALS AND METHODS Immunochemistry was performed to investigate the Mena and tumor-related markers expression, and its clinicopathological characteristics in 46 TSCC specimens. TSCC cell SCC9 and Cal27 untransfected or stable transfected with Mena overexpression and small interfering RNA were used to determine the role of Mena in cell proliferation, cell migration, invasion and metastasis, and EMT-related markers in vitro, and the effect of Mena on TSCC growth and metastasis through tumor-bearing and tumor metastasis immunodeficient mice models in vivo. RESULTS Immunochemistry showed that the expression of Mena was significantly correlated with lymphatic metastasis and TNM stage, E-cadherin, Vimentin, and MMP2. Mena did not affect cell proliferation and colony formation in vitro, and tumor growth in vivo. However, it promoted cell migration and invasion in vitro, and TSCC metastasis in vivo. CONCLUSIONS Mena expression is associated with lymphatic metastasis and tumor stage and promotes TSCC invasion and metastasis by inducing the EMT process. Thus, Mena may be a biomarker for prognosis and targeted therapy in TSCC patients.
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Affiliation(s)
- Hao Cui
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Xiang Liang
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Yifei Zhu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Sadam Ahmed Elayah
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Hong Qi
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Pathology, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Linyang Xie
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Zhichen Guo
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Fang Siya
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Yu Ming
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Gong Yuxin
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Junbo Tu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Sijia Na
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
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Wei QY, Jin F, Wang ZY, Li BJ, Cao WB, Sun ZY, Mo SJ. MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma. World J Gastroenterol 2024; 30:1497-1523. [PMID: 38617454 PMCID: PMC11008420 DOI: 10.3748/wjg.v30.i11.1497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 01/12/2024] [Accepted: 03/01/2024] [Indexed: 03/21/2024] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.
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Affiliation(s)
- Qi-Ying Wei
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Feng Jin
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Zhong-Yu Wang
- Department of Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Bing-Jie Li
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Wen-Bo Cao
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Zhi-Yan Sun
- Division of Special Service, Department of Basic Oncology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Sai-Jun Mo
- Department of Basic Science of Oncology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
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Mazloomi S, Mousavi V, Aghadavod E, Mafi A. Circular RNAs: Emerging Modulators in the Pathophysiology of Polycystic Ovary Syndrome and their Clinical Implications. Curr Mol Med 2024; 24:153-166. [PMID: 36627779 DOI: 10.2174/1566524023666230110151155] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 11/17/2022] [Accepted: 11/22/2022] [Indexed: 01/12/2023]
Abstract
Polycystic ovary syndrome (PCOS) is a prevalent endocrine/metabolic disorder in women of reproductive age. PCOS is characterized by hyperandrogenism, polycystic ovary morphology, and ovulatory dysfunction/anovulation. It involves multiple effects in patients, including granulosa/theca cell hyperplasia, menstrual disturbances, infertility, acne, obesity, insulin resistance, and cardiovascular disorders. Biochemical analyses and the results of RNA sequencing studies in recent years have shown a type of non-coding RNAs as a splicing product known as circular RNAs (circRNAs). Several biological functions have been identified in relation to circRNAs, including a role in miRNA sponge, protein sequestration, increased parental gene expression, and translation leading to polypeptides. These circular molecules are more plentiful and specialized than other types of RNAs. For this reason, they are referred to as potential biomarkers in different diseases. Evidence suggests that circRNAs may have regulatory potentials through different signaling pathways, such as the miRNA network. Probably most experts in the field of obstetricians are not aware of circRNAs as a useful biomarker. Therefore, this review focused on the researches that have been done on the involvement of circRNAs in PCOS and summarized recent supportive evidence, and evaluated the circRNA association and mechanisms involved in PCOS.
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Affiliation(s)
- Sahar Mazloomi
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Vahide Mousavi
- School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Esmat Aghadavod
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
- Department of Clinical Biochemistry, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Alireza Mafi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
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Zhang X, Chen X, Sun D, Song N, Li M, Zheng W, Yu Y, Ding G, Jiang Y. ENAH-202 promotes cancer progression in oral squamous cell carcinoma by regulating ZNF502/VIM axis. Cancer Med 2023; 12:20892-20905. [PMID: 37902191 PMCID: PMC10709750 DOI: 10.1002/cam4.6652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 09/22/2023] [Accepted: 09/26/2023] [Indexed: 10/31/2023] Open
Abstract
BACKGROUND We aimed to demonstrate the regulatory effect of long non-coding RNA (lncRNA) ENAH-202 on oral squamous cell carcinoma (OSCC) development as well as its molecular mechanism. METHODS We detected ENAH-202 expression in OSCC tissues and cell lines by quantitative real-time PCR (qPCR). The biological function of ENAH-202 was assessed in vitro and in vivo using CCK-8, colony formation assays, transwell assays, xenograft formation, and tail vein injection. The further molecular mechanism by which ENAH-202 promoted OSCC progression was identified using RNA pull-down, LS-MS/MS analysis, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) assays. RESULTS ENAH-202 was significantly upregulated in OSCC tissues and cells. ENAH-202 promoted OSCC cell proliferation, migration, and invasion in vitro and in vivo. The expression of enabled homolog (ENAH) and epithelial-to-mesenchymal transition (EMT)-related proteins was changed with the expression of ENAH-202. Moreover, ENAH-202 promoted the transcription of Vimentin (VIM) by binding with ZNF502, which can help ENAH-202 promote OSCC progression. CONCLUSIONS ENAH-202 facilitated OSCC cell proliferation and metastasis by regulating ZNF502/VIM axis, which played an important role in OSCC progression.
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Affiliation(s)
- Xinyue Zhang
- School of StomatologyWeifang Medical UniversityWeifangShandongChina
- Weifang Key Laboratory of Oral BiomedicineWeifang Medical UniversityWeifangShandongChina
| | - Xi Chen
- School of StomatologyWeifang Medical UniversityWeifangShandongChina
- Weifang Key Laboratory of Oral BiomedicineWeifang Medical UniversityWeifangShandongChina
| | - Dongyuan Sun
- School of StomatologyWeifang Medical UniversityWeifangShandongChina
- Weifang Key Laboratory of Oral BiomedicineWeifang Medical UniversityWeifangShandongChina
| | - Ning Song
- School of StomatologyWeifang Medical UniversityWeifangShandongChina
- Weifang Key Laboratory of Oral BiomedicineWeifang Medical UniversityWeifangShandongChina
| | - Minmin Li
- School of StomatologyWeifang Medical UniversityWeifangShandongChina
- Weifang Key Laboratory of Oral BiomedicineWeifang Medical UniversityWeifangShandongChina
| | - Wentian Zheng
- School of StomatologyWeifang Medical UniversityWeifangShandongChina
- Weifang Key Laboratory of Oral BiomedicineWeifang Medical UniversityWeifangShandongChina
| | - Yang Yu
- School of StomatologyWeifang Medical UniversityWeifangShandongChina
- Weifang Key Laboratory of Oral BiomedicineWeifang Medical UniversityWeifangShandongChina
| | - Gang Ding
- School of StomatologyWeifang Medical UniversityWeifangShandongChina
- Weifang Key Laboratory of Oral BiomedicineWeifang Medical UniversityWeifangShandongChina
| | - Yingying Jiang
- School of StomatologyWeifang Medical UniversityWeifangShandongChina
- Weifang Key Laboratory of Oral BiomedicineWeifang Medical UniversityWeifangShandongChina
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10
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Cui Y, Wu Y, Zhu Y, Liu W, Huang L, Hong Z, Zhang M, Zheng X, Sun G. The possible molecular mechanism underlying the involvement of the variable shear factor QKI in the epithelial-mesenchymal transformation of oesophageal cancer. PLoS One 2023; 18:e0288403. [PMID: 37428781 DOI: 10.1371/journal.pone.0288403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Accepted: 06/26/2023] [Indexed: 07/12/2023] Open
Abstract
OBJECTIVE Based on the GEO, TCGA and GTEx databases, we reveal the possible molecular mechanism of the variable shear factor QKI in epithelial mesenchymal transformation (EMT) of oesophageal cancer. METHODS Based on the TCGA and GTEx databases, the differential expression of the variable shear factor QKI in oesophageal cancer samples was analysed, and functional enrichment analysis of QKI was performed based on the TCGA-ESCA dataset. The percent-spliced in (PSI) data of oesophageal cancer samples were downloaded from the TCGASpliceSeq database, and the genes and variable splicing types that were significantly related to the expression of the variable splicing factor QKI were screened out. We further identified the significantly upregulated circRNAs and their corresponding coding genes in oesophageal cancer, screened the EMT-related genes that were significantly positively correlated with QKI expression, predicted the circRNA-miRNA binding relationship through the circBank database, predicted the miRNA-mRNA binding relationship through the TargetScan database, and finally obtained the circRNA-miRNA-mRNA network through which QKI promoted the EMT process. RESULTS Compared with normal control tissue, QKI expression was significantly upregulated in tumour tissue samples of oesophageal cancer patients. High expression of QKI may promote the EMT process in oesophageal cancer. QKI promotes hsa_circ_0006646 and hsa_circ_0061395 generation by regulating the variable shear of BACH1 and PTK2. In oesophageal cancer, QKI may promote the production of the above two circRNAs by regulating variable splicing, and these circRNAs further competitively bind miRNAs to relieve the targeted inhibition of IL-11, MFAP2, MMP10, and MMP1 and finally promote the EMT process. CONCLUSION Variable shear factor QKI promotes hsa_circ_0006646 and hsa_circ_0061395 generation, and downstream related miRNAs can relieve the targeted inhibition of EMT-related genes (IL11, MFAP2, MMP10, MMP1) and promote the occurrence and development of oesophageal cancer, providing a new theoretical basis for screening prognostic markers of oesophageal cancer patients.
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Affiliation(s)
- Yishuang Cui
- School of Public Health, North China University of Science and Technology, Tangshan, Hebei Province, China
- Department of Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, Tangshan, Hebei Province, China
| | - Yanan Wu
- School of Public Health, North China University of Science and Technology, Tangshan, Hebei Province, China
- Department of Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, Tangshan, Hebei Province, China
| | - Yingze Zhu
- Department of Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, Tangshan, Hebei Province, China
- School of Clinical Medicine, North China University of Science and Technology, Tangshan, Hebei Province, China
- Affiliated Hospital, North China University of Science and Technology, Tangshan, Hebei Province, China
| | - Wei Liu
- Department of Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, Tangshan, Hebei Province, China
- School of Clinical Medicine, North China University of Science and Technology, Tangshan, Hebei Province, China
- Affiliated Hospital, North China University of Science and Technology, Tangshan, Hebei Province, China
| | - Lanxiang Huang
- Department of Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, Tangshan, Hebei Province, China
- School of Clinical Medicine, North China University of Science and Technology, Tangshan, Hebei Province, China
- Affiliated Hospital, North China University of Science and Technology, Tangshan, Hebei Province, China
| | - Ziqian Hong
- School of Public Health, North China University of Science and Technology, Tangshan, Hebei Province, China
- Department of Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, Tangshan, Hebei Province, China
| | - Mengshi Zhang
- School of Public Health, North China University of Science and Technology, Tangshan, Hebei Province, China
- Department of Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, Tangshan, Hebei Province, China
| | - Xuan Zheng
- School of Public Health, North China University of Science and Technology, Tangshan, Hebei Province, China
- Department of Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, Tangshan, Hebei Province, China
| | - Guogui Sun
- School of Public Health, North China University of Science and Technology, Tangshan, Hebei Province, China
- Department of Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, Tangshan, Hebei Province, China
- School of Clinical Medicine, North China University of Science and Technology, Tangshan, Hebei Province, China
- Affiliated Hospital, North China University of Science and Technology, Tangshan, Hebei Province, China
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Liu A, Jiang B, Song C, Zhong Q, Mo Y, Yang R, Chen C, Peng C, Peng F, Tang H. Isoliquiritigenin inhibits circ0030018 to suppress glioma tumorigenesis via the miR-1236/HER2 signaling pathway. MedComm (Beijing) 2023; 4:e282. [PMID: 37250146 PMCID: PMC10220153 DOI: 10.1002/mco2.282] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 04/22/2023] [Accepted: 04/22/2023] [Indexed: 05/31/2023] Open
Abstract
In the central nervous system diseases, glioma is one of the most common malignancies around the world. Despite the recent improvements in therapies for glioma, the prognosis of some high-risk glioma remains poor. In glioma, isoliquiritigenin (ISL) is reported to have antioxidative and antitumor activities. However, the potential mechanisms between ISL and circle RNAs (circRNAs) in the glioma tumorigenesis process have not yet been reported. Here, we treated glioma cells with ISL, and circRNA expression levels were detected. Circ0030018 was found significantly downregulated by ISL. Therefore, we explored circ0030018 expression profiles and functions in glioma, finding that circ0030018 was evidently overexpressed in glioma cell lines. Colony formation, CCK-8, and transwell assay made clear that circ0030018 silencing dramatically cut down glioma growth and invasion. Moreover, ROS level was detected to find that circ0030018 silence remarkably enhanced cell oxidative stress in glioma. Mechanism studies were conducted to investigate the underlying basis of circ0030018 function in glioma, unveiling that circ0030018 realized its functions partially through the miR-1236/HER2 signaling in glioma. In conclusion, our study investigated the roles and mechanisms of the ISL on the circ0030018/miR-1236/HER2 pathway in glioma tumorigenesis and progression. Circ0030018 could act as the prospective biologic signature or therapeutic target for glioma.
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Affiliation(s)
- Aiqun Liu
- Department of NeurologySchool of Clinical Medicine the First Affiliated Hospital of Guangdong Pharmaceutical UniversityGuangzhouChina
| | - Baohong Jiang
- Department of Pharmacy, the First Affiliated Hospital, Hengyang Medical SchoolUniversity of South ChinaHengyangChina
| | - Cailu Song
- State Key Laboratory of Oncology in South ChinaSun Yat‐sen University Cancer CenterGuangzhouChina
| | - Qizhi Zhong
- Department of NeurologySchool of Clinical Medicine the First Affiliated Hospital of Guangdong Pharmaceutical UniversityGuangzhouChina
| | - Yufan Mo
- Department of NeurologySchool of Clinical Medicine the First Affiliated Hospital of Guangdong Pharmaceutical UniversityGuangzhouChina
| | - Ruiqin Yang
- Department of NeurologySchool of Clinical Medicine the First Affiliated Hospital of Guangdong Pharmaceutical UniversityGuangzhouChina
| | - Ciyu Chen
- Department of NeurologySchool of Clinical Medicine the First Affiliated Hospital of Guangdong Pharmaceutical UniversityGuangzhouChina
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine ResourcesChengdu University of Traditional Chinese MedicineChengduChina
| | - Fu Peng
- West China School of PharmacySichuan UniversityChengduChina
| | - Hailin Tang
- State Key Laboratory of Oncology in South ChinaSun Yat‐sen University Cancer CenterGuangzhouChina
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12
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Na S, Cui H, Guo Z, Liang X, Sakran KA, Guo X, Li X, Xie L, Zhu Y, Qi H, Tu J. Overexpression of Mena is associated with tumor progression and poor prognosis in oral squamous cell carcinoma via EMT. Front Oncol 2022; 12:1052375. [PMID: 36620546 PMCID: PMC9822539 DOI: 10.3389/fonc.2022.1052375] [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: 09/23/2022] [Accepted: 12/05/2022] [Indexed: 12/24/2022] Open
Abstract
Background Mena, a cytoskeletal regulatory protein, is involved in actin-based regulation of cell motility and adhesion, and contributes to tumor invasion and metastasis. However, the role of Mena in oral squamous cell carcinoma remains unclear. This is the first research focusing on the prognostic value of Mena in OSCC. In this study, we aimed to investigate the correlation between Mena expression and clinicopathological significance, as well as prognostic value in OSCC. Methods Mena gene expression profiles of OSCC and normal tissues were collected from Oncomine, TCGA, and GEO databases. Biological function was analyzed through GO, KEGG and GSEA enrichment. Further, the expression level of Mena and tumor-related markers in 151 OSCC specimens was examined by IHC staining based on tissue microarray. Kaplan-Meier analysis was used to assess the prognostic performance of Mena in OSCC. Result Mena was generally upregulation in various malignancies, especially OSCC. The functional analyses indicated that Mena was involved in the assembly and regulation of actin, cell movement, and EMT. IHC staining revealed that high expression of Mena in OSCC was correlated with Lymphatic metastasis, TNM stage, E-cadherin, Vimentin, and MMP-2, but insignificantly Ki67. Kaplan-Meier analysis demonstrated that elevated expression of Mena was significantly associated with poor overall survival and disease-free survival of OSCC patients. Conclusion Mena could be a novel biomarker for predicting the prognosis of OSCC patients, which supports a theoretical basis for developing molecular target therapy.
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Affiliation(s)
- Sijia Na
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China,Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Hao Cui
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China,Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Zhichen Guo
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China,Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xiang Liang
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China,Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Karim Ahmed Sakran
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China,Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Xiaomei Guo
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China,Department of Pathology, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xingqiang Li
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China,Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Linyang Xie
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China,Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Yifei Zhu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China,Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Hong Qi
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China,Department of Pathology, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China,*Correspondence: Hong Qi, ; Junbo Tu,
| | - Junbo Tu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China,Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi, China,*Correspondence: Hong Qi, ; Junbo Tu,
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Fang X, Shrestha SM, Ren L, Shi R. Biological and clinical implications of metastasis-associated circular RNAs in oesophageal squamous cell carcinoma. FEBS Open Bio 2021; 11:2870-2887. [PMID: 34510785 PMCID: PMC8564336 DOI: 10.1002/2211-5463.13297] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 08/29/2021] [Accepted: 09/10/2021] [Indexed: 12/20/2022] Open
Abstract
Oesophageal squamous cell carcinoma (OSCC) is a prevalent malignancy with high morbidity and mortality as a result of early metastasis and poor prognosis. Metastasis is a multistep process, involving various signalling pathways. Circular RNAs (circRNAs) are a class of covalently closed noncoding RNAs, the aberrant expression of which is reported to be involved in several biological events, including cell transformation, proliferation, migration, invasion, apoptosis and metastasis. Several studies have reported interactions between circRNAs and metastasis-associated signalling pathways. The abundance, stability and highly specific expression of candidate circRNAs make them potential biomarkers and therapeutic targets in OSCC. In this review article, we comprehensively describe metastasis-related circRNAs and their interactions with epithelial-mesenchymal transition-associated molecules. We also describe the molecular mechanisms and clinical relevance of circRNAs in OSCC progression and metastasis.
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Affiliation(s)
- Xin Fang
- Medical CollegeSoutheast UniversityNanjingChina
| | | | - Li‐Hua Ren
- Medical CollegeSoutheast UniversityNanjingChina
- Department of GastroenterologyZhongda HospitalAffiliated Hospital of Southeast UniversityNanjingChina
| | - Rui‐hua Shi
- Medical CollegeSoutheast UniversityNanjingChina
- Department of GastroenterologyZhongda HospitalAffiliated Hospital of Southeast UniversityNanjingChina
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14
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Peng H, Sun J, Li Y, Zhang Y, Zhong Y. Circ-USP9X Inhibition Reduces Oxidized Low-density Lipoprotein-induced Endothelial Cell Injury via the microRNA 599/Chloride Intracellular Channel 4 Axis. J Cardiovasc Pharmacol 2021; 78:560-571. [PMID: 34269702 DOI: 10.1097/fjc.0000000000001104] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 05/29/2021] [Indexed: 11/27/2022]
Abstract
ABSTRACT Atherosclerosis (AS) is the common pathological basis of cardiovascular disease. Circular RNA circ-USP9X (hsa_circ_0090231) has been discovered to be upregulated in oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs), but the role of circ-USP9X in ox-LDL-induced endothelial cell injury is indistinct. The purpose of the research was to investigate the role and regulatory mechanism of circ-USP9X in ox-LDL--induced endothelial cell injury. Expression of circ-USP9X was examined by quantitative real-time polymerase chain reaction. Loss-of-function experiments were performed to assess the impacts of circ-USP9X inhibition on viability, cell cycle progression, apoptosis, and tube formation, inflammation, and oxidative stress of ox-LDL-induced HUVEC. The regulatory mechanism of circ-USP9X predicted by bioinformatics analysis and verified by dual-luciferase reporter or RNA immunoprecipitation assays. We observed that circ-USP9X was upregulated in AS patients' serum and ox-LDL-induced HUVEC. Inhibition of circ-USP9X elevated viability, promoted cell cycle progression and angiopoiesis, and decreased apoptosis, inflammation, and oxidative stress of ox-LDL-induced HUVEC. Mechanically, circ-USP9X regulated chloride intracellular channel 4 (CLIC4) messenger RNA expression by sponging microRNA (miR)-599. Furthermore, miR-599 inhibitor overturned circ-USP9X silencing-mediated influence on ox-LDL-induced HUVEC injury. Also, CLIC4 overexpression reversed miR-599 elevation-mediated effect on ox-LDL-induced HUVEC injury. In conclusion, circ-USP9X silencing decreased ox-LDL-induced endothelial cell injury via the miR-599/CLIC4 axis, which offered a novel molecular mechanism to comprehend the pathology of AS.
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Affiliation(s)
- Huaiyu Peng
- Department of Vascular Intervention, The Ninth Hospital of Xi'an, Xi'an City, Shanxi Province, China ; and
| | - Jihu Sun
- Department of Oncology, Xi'an Hospital of Traditional Chinese Medicine, Xi'an City, Shanxi Province, China
| | - Yi Li
- Department of Vascular Intervention, The Ninth Hospital of Xi'an, Xi'an City, Shanxi Province, China ; and
| | - Ye Zhang
- Department of Vascular Intervention, The Ninth Hospital of Xi'an, Xi'an City, Shanxi Province, China ; and
| | - Yongjin Zhong
- Department of Vascular Intervention, The Ninth Hospital of Xi'an, Xi'an City, Shanxi Province, China ; and
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He Y, Chen Y, Tong Y, Long W, Liu Q. Identification of a circRNA-miRNA-mRNA regulatory network for exploring novel therapeutic options for glioma. PeerJ 2021; 9:e11894. [PMID: 34434651 PMCID: PMC8351580 DOI: 10.7717/peerj.11894] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 07/12/2021] [Indexed: 12/19/2022] Open
Abstract
Background Glioma is the most common brain neoplasm with a poor prognosis. Circular RNA (circRNA) and their associated competing endogenous RNA (ceRNA) network play critical roles in the pathogenesis of glioma. However, the alteration of the circRNA-miRNA-mRNA regulatory network and its correlation with glioma therapy haven't been systematically analyzed. Methods With GEO, GEPIA2, circBank, CSCD, CircInteractome, mirWalk 2.0, and mirDIP 4.1, we constructed a circRNA-miRNA-mRNA network in glioma. LASSO regression and multivariate Cox regression analysis established a hub mRNA signature to assess the prognosis. GSVA was used to estimate the immune infiltration level. Potential anti-glioma drugs were forecasted using the cMap database and evaluated with GSEA using GEO data. Results A ceRNA network of seven circRNAs (hsa_circ_0030788/0034182/0000227/ 0018086/0000229/0036592/0002765), 15 miRNAs(hsa-miR-1200/1205/1248/ 1303/3925-5p/5693/581/586/599/607/640/647/6867-5p/767-3p/935), and 46 mRNAs (including 11 hub genes of ARHGAP11A, DRP2, HNRNPA3, IGFBP5, IP6K2, KLF10, KPNA4, NRP2, PAIP1, RCN1, and SEMA5A) was constructed. Functional enrichment showed they influenced majority of the hallmarks of tumors. Eleven hub genes were proven to be decent prognostic signatures for glioma in both TCGA and CGGA datasets. Forty-six LASSO regression significant genes were closely related to immune infiltration. Finally, five compounds (fulvestrant, tanespimycin, mifepristone, tretinoin, and harman) were predicted as potential treatments for glioma. Among them, mifepristone and tretinoin were proven to inhibit the cell cycle and DNA repair in glioma. Conclusion This study highlights the potential pathogenesis of the circRNA-miRNA-mRNA regulatory network and identifies novel therapeutic options for glioma.
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Affiliation(s)
- Yi He
- Neurosurgery Department, Xiangya Hospital Central South University, Changsha, Hunan, China
| | - Yihong Chen
- Neurosurgery Department, Xiangya Hospital Central South University, Changsha, Hunan, China
| | - Yuxin Tong
- Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, China
| | - Wenyong Long
- Neurosurgery Department, Xiangya Hospital Central South University, Changsha, Hunan, China
| | - Qing Liu
- Neurosurgery Department, Xiangya Hospital Central South University, Changsha, Hunan, China
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Qu F, Wang L, Wang C, Yu L, Zhao K, Zhong H. Circular RNA circ_0006168 enhances Taxol resistance in esophageal squamous cell carcinoma by regulating miR-194-5p/JMJD1C axis. Cancer Cell Int 2021; 21:273. [PMID: 34022910 PMCID: PMC8141117 DOI: 10.1186/s12935-021-01984-y] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 05/13/2021] [Indexed: 12/24/2022] Open
Abstract
Background Chemoresistance is one of the major obstacles for cancer therapy in the clinic. Circular RNAs (circRNAs) are involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC) and chemoresistance. This study aimed to explore the role and molecular mechanism of circ_0006168 in Taxol resistance of ESCC. Methods The expression levels of circ_0006168, microRNA-194-5p (miR-194-5p) and jumonji domain containing 1C (JMJD1C) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The half-inhibition concentration (IC50) value of Taxol was evaluated by Cell Counting Kit-8 (CCK-8) assay. Cell proliferation was evaluated by CCK-8 and colony formation assays. Cell migration and invasion were detected by transwell assay. Cell apoptosis was determined by flow cytometry. The interaction between miR-194-5p and circ_0006168 or JMJD1C was predicted by bioinformatics analysis (Circinteractome and TargetScan) and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) and RNA pull-down assays. The mice xenograft model was established to investigate the roles of circ_0006168 in vivo. Results Circ_0006168 and JMJD1C were upregulated and miR-194-5p was downregulated in ESCC tissues, ESCC cells, and Taxol-resistant cells. Functionally, knockdown of circ_0006168 or JMJD1C increased Taxol sensitivity of ESCC in vitro via inhibiting cell proliferation, migration and invasion, and promoting apoptosis. Moreover, circ_0006168 could directly bind to miR-194-5p and JMJD1C was verified as a direct target of miR-194-5p. Mechanically, circ_0006168 was a sponge of miR-194-5p to regulate JMJD1C expression in ESCC cells. Furthermore, JMJD1C overexpression reversed the promotive effect of circ_0006168 knockdown on Taxol sensitivity. Besides, circ_0006168 silence suppressed tumor growth in vivo. Conclusion Circ_0006168 facilitated Taxol resistance in ESCC by regulating miR-194-5p/JMJD1C axis, providing a promising therapeutic target for ESCC chemotherapy. Supplementary Information The online version contains supplementary material available at 10.1186/s12935-021-01984-y.
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Affiliation(s)
- Fanyong Qu
- Department of Radiation Oncology, Yantai Affiliated Hospital of Binzhou Medical University, No. 717, Jinbu Street, Mu ping District, Yantai, Shandong, 264100, China.
| | - Lina Wang
- Department of Oncology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, 264100, China
| | - Caiyan Wang
- Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, 264100, China
| | - Lingxia Yu
- Department of Oncology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, 264100, China
| | - Kaikai Zhao
- Department of Radiation Oncology, Yantai Affiliated Hospital of Binzhou Medical University, No. 717, Jinbu Street, Mu ping District, Yantai, Shandong, 264100, China
| | - Hao Zhong
- Department of Radiation Oncology, Yantai Affiliated Hospital of Binzhou Medical University, No. 717, Jinbu Street, Mu ping District, Yantai, Shandong, 264100, China
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Circular RNA hsa_circ_0072309 inhibits non-small cell lung cancer progression by sponging miR-580-3p. Biosci Rep 2021; 40:222657. [PMID: 32293004 PMCID: PMC7199450 DOI: 10.1042/bsr20194237] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Revised: 03/24/2020] [Accepted: 03/31/2020] [Indexed: 12/13/2022] Open
Abstract
Objective: Non-small cell lung cancer (NSCLC) continues to top the list of cancer mortalities worldwide. Early diagnosis and therapeutic interventions targeting NSCLC is becoming the world’s significant challenge. Circular RNAs (circRNAs) are emerging as a group of potential cancer biomarkers. Materials and methods: Quantitative real-time PCR (qRT-PCR) was employed to examine the expression of circ_0072309 in NSCLC tissues and cell lines. Cell counting kit 8 (CCK-8), wound healing and Transwell assays were used to analyze cell proliferation, migration and invasion in A549 and H1299 cells. The relationship between circ_0072309 and miR-580-3 was analyzed by Luciferase reporter and RNA pull down assays. Results: We screened circ_0072309 from Gene Expression Omnibus and found that circ_0072309 was lowly expressed in NSCLC tissues and cell lines. The transfection of circ_0072309-overexpressing vector significantly suppressed the cell proliferation, migration and invasion in A549 and H1299 cells. We predicted that miR-580-3p is a target of circ_0072309 by using publicly available bioinformatic algorithms Circinteractome tool and confirmed that circ_0072309 directly bound to miR-580-3p. Furthermore, the addition of miR-580-3p mitigated the blockage of cell proliferation, migration and invasion induced by circ_0072309. Conclusions: These data showed that circ_0072309 inhibits the progression of NSCLC progression via blocking the expression of miR-580-3p. These findings revealed the anti-tumor role of circ_0072309 during the development of NSCLC and provided a novel diagnostic biomarker and potential therapy for NSCLC.
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CircRNAs: a new target for the diagnosis and treatment of digestive system neoplasms. Cell Death Dis 2021; 12:205. [PMID: 33627631 PMCID: PMC7904779 DOI: 10.1038/s41419-021-03495-0] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 01/27/2021] [Accepted: 02/01/2021] [Indexed: 02/06/2023]
Abstract
A circRNA is a type of endogenous noncoding RNA that consists of a closed circular RNA molecule formed by reverse splicing; these RNAs are widely distributed in a variety of biological cells. In contrast to linear RNAs, circRNAs have no 5′ cap or 3′ poly(A) tail. They have a stable structure, a high degree of conservation, and high stability, and they are richly and specifically expressed in certain tissues and developmental stages. CircRNAs play a very important role in the occurrence and progression of malignant tumors. According to their origins, circRNAs can be divided into four types: exon-derived circRNAs (ecRNAs), intron-derived circRNAs (ciRNAs), circRNAs containing both exons and introns (EIciRNAs) and intergenic circRNAs. A large number of studies have shown that circRNAs have a variety of biological functions, participate in the regulation of gene expression and play an important role in the occurrence and progression of tumors. In this paper, the structure and function of circRNAs are reviewed, along with their biological role in malignant tumors of the digestive tract, in order to provide a reference for the diagnosis and treatment of digestive system neoplasms.
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Zhu Z, Shen S, Zhao S, Wang Z. Hsa_circ_0006916 Knockdown Represses the Development of Hepatocellular Carcinoma via Modulating miR-599/SRSF2 Axis. Onco Targets Ther 2020; 13:11301-11313. [PMID: 33177838 PMCID: PMC7649248 DOI: 10.2147/ott.s267471] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 09/22/2020] [Indexed: 12/12/2022] Open
Abstract
Background The aberrantly expressed circular RNAs (circRNAs) are implicated in the progression of hepatocellular carcinoma (HCC). CircRNA hsa_circ_0006916 (circ_0006916) is dysregulated in HCC, but the function and mechanism of this circRNA in HCC development remain uncertain. Methods Thirty paired HCC and normal tissues were collected. circ_0006916, microRNA (miR)-599 and serine/arginine rich splicing factor 2 (SRSF2) abundances were examined via quantitative reverse transcription polymerase chain reaction or Western blot. Cell viability, colony ability, migration, invasion, cell cycle and apoptosis were tested via cell counting kit-8, colony formation, wound healing analysis, transwell analysis, and flow cytometry. The interaction between miR-599 and circ_0006916 or SRSF2 was analyzed via dual-luciferase reporter and RNA immunoprecipitation analyses. The function of circ_0006916 on cell growth in vivo was analyzed via xenograft model. Results circ_0006916 expression was increased in HCC tissues and cell lines. circ_0006916 knockdown reduced cell viability, colony formation, migration and invasion and caused cell cycle arrest and apoptosis. miR-599 was targeted via circ_0006916, and miR-599 knockdown reversed the influence of circ_0006916 silence on HCC progression. SRSF2 was targeted via miR-599, and miR-599 overexpression suppressed cell viability, colony formation, migration and invasion and promoted cell cycle arrest and apoptosis via decreasing SRSF2. circ_0006916 could regulate SRSF2 expression via miR-599. circ_0006916 knockdown decreased HCC cell growth in the xenograft model. Conclusion circ_0006916 knockdown represses the progression of HCC via regulating miR-599 and SRSF2.
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Affiliation(s)
- Zhixiang Zhu
- Image Center, The First Affiliated Hospital of Henan University, Kaifeng, Henan 475001, People's Republic of China
| | - Songhe Shen
- Image Center, The First Affiliated Hospital of Henan University, Kaifeng, Henan 475001, People's Republic of China
| | - Sen Zhao
- Image Center, The First Affiliated Hospital of Henan University, Kaifeng, Henan 475001, People's Republic of China
| | - Zhixue Wang
- Image Center, The First Affiliated Hospital of Henan University, Kaifeng, Henan 475001, People's Republic of China
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Abstract
As a new kind of RNA, circular RNA (circRNA) is a endogenous non-coding RNA with circular structure, which has the characteristics of universality, stability, conservatism and specificity. CircRNA can specifically bind to microRNAs (miRNAs) in the form of competitive endogenous RNA, thus directly or indirectly regulating the expression of related genes. In addition to the role of sponge, circRNA also regulates parental gene expression, transcriptional translation and protein modification; and it can be used as a biomarker to develop potential diagnosis and treatment methods and evaluate prognosis. Due to changes in dietary habits and genetic factors, the morbidity and mortality of esophageal cancer (EC) in the world are still high, and are prone to early metastasis. Although the diagnosis and treatment techniques have been improved in recent years, the early diagnosis of EC is not common, and the 5-year survival rate of patients is still very low. This article reviews the function and significance of circRNA and discusses the research progress of circRNA as biomarkers in EC.
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Li C, Tian Y, Liang Y, Li Q. Circ_0008035 contributes to cell proliferation and inhibits apoptosis and ferroptosis in gastric cancer via miR-599/EIF4A1 axis. Cancer Cell Int 2020; 20:84. [PMID: 32190008 PMCID: PMC7076943 DOI: 10.1186/s12935-020-01168-0] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Accepted: 03/09/2020] [Indexed: 12/12/2022] Open
Abstract
Background Currently, multiple circular RNAs (circRNAs) have been verified to act as essential regulators in the progression of gastric cancer (GC). We aimed to investigate the role of circ_0008035 in GC progression. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to measure the expression of circ_0008035 and miR-599. 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was employed to evaluate cell proliferation and ferroptosis. Western blot assay was performed to measure the levels of cyclin D1, proliferating cell nuclear antigen (PCNA) and eukaryotic initiation factor 4A1 (EIF4A1). Flow cytometry analysis was conducted to assess cell apoptosis. The iron accumulation, lipid peroxidation and mitochondrial membrane potential were examined by relevant kits. Dual-luciferase reporter assay was conducted to determine the targeting relationship between miR-599 and circ_0008035 or EIF4A1. A murine xenograft model was established to investigate the function of circ_0008035 in vivo. Results Circ_0008035 was up-regulated in GC tissues and cells. Silencing of circ_0008035 repressed cell proliferation and induced cell apoptosis and ferroptosis in GC cells. Circ_0008035 acted as a sponge of miR-599. The effects of circ_0008035 knockdown on GC cell proliferation, apoptosis and ferroptosis were abolished by miR-599 inhibition. EIF4A1 was confirmed to be a target gene of miR-599. Circ_0008035 knockdown inhibited EIF4A1 expression by targeting miR-599. Moreover, the suppressive role of circ_0008035 deficiency in GC progression could be restored by EIF4A1. Additionally, circ-0008035 knockdown hampered tumorigenesis in vivo. Conclusion Circ_0008035 promoted GC cell growth and repressed apoptosis and ferroptosis by up-regulating EIF4A1 through sponging miR-599.
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Affiliation(s)
- Chang Li
- 1Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No.126, Xiantai Street, Changchun, 130031 Jilin China
| | - Yuan Tian
- 2Center of Physical Examination, China-Japan Union Hospital of Jilin University, Changchun, 130031 Jilin China
| | - Yun Liang
- 2Center of Physical Examination, China-Japan Union Hospital of Jilin University, Changchun, 130031 Jilin China
| | - Qingchun Li
- 1Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No.126, Xiantai Street, Changchun, 130031 Jilin China
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