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1
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Wang P, Li G, Sun X, Zhang J, Shi L, Zhou X, Wang G, Chen W. miR-182-5p facilitates colorectal cancer progression through manipulating neurocalcin delta mediated Wnt/β-catenin signalling. Eur J Med Res 2025; 30:352. [PMID: 40312722 PMCID: PMC12046800 DOI: 10.1186/s40001-025-02625-0] [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: 11/08/2024] [Accepted: 04/22/2025] [Indexed: 05/03/2025] Open
Abstract
BACKGROUND Colorectal cancer (CRC), a complex and multifactorial disease, has been associated with elevated expression of microRNA miR-182-5p, although its precise regulatory role in CRC progression remains unclear. This study aims to identify potential therapeutic targets to improve clinical outcomes and to decipher the intricate role of miR-182-5p in the pathobiology of CRC. METHODS We conducted comprehensive bioinformatics analyses using GEO databases to investigate differences in miRNA expression between CRC and normal tissues, with a particular focus on miR-182-5p. Its expression levels in CRC cells and tumor tissues were quantified by quantitative real-time PCR (qRT-PCR). The expression of neurocalcin delta (NCALD) and proteins related to Wnt/β-catenin signalling was evaluated by qRT-PCR and Western blotting. Pathological changes in tumor-bearing mice as well as the proliferation, invasion, and migration of CRC cells, were assessed. Tumor cell proliferation and apoptosis were examined using Ki-67 immunohistochemistry and TUNEL staining, respectively. A dual luciferase reporter assay explored the regulatory interaction between miR-182-5p and NCALD. RESULTS Our findings reveal significantly elevated miR-182-5p levels in CRC tissues and cell lines, positively correlated with tumor invasion depth, differentiation degree, clinical stage, and lymph node metastasis. miR-182-5p appears to accelerate CRC progression in both cell lines and mouse models by downregulating NCALD, thereby enhancing Wnt/β-catenin signalling. This study identifies miR-182-5p as a pivotal enhancer of CRC progression, modulating Wnt/β-catenin signalling via NCALD regulation. CONCLUSIONS The findings position the miR-182-5p/NCALD axis as promising targets for CRC therapy, offering new avenues for treatment strategies. TRIAL REGISTRATION Retrospectively registered.
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Affiliation(s)
- Pengfei Wang
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China
- Department of Gastroenterology, Affiliated Qidong Hospital of Nantong University, Qidong, 226200, Jiangsu, China
| | - Gang Li
- Institute of Special Environmental Medicine, Nantong University, Chongchuan District, 9 Seyuan Road, Nantong, 226019, Jiangsu, China
| | - Xianglin Sun
- Institute of Special Environmental Medicine, Nantong University, Chongchuan District, 9 Seyuan Road, Nantong, 226019, Jiangsu, China
| | - Jie Zhang
- Department of Gastroenterology, Affiliated Qidong Hospital of Nantong University, Qidong, 226200, Jiangsu, China
| | - Leijian Shi
- Department of Gastroenterology, Affiliated Qidong Hospital of Nantong University, Qidong, 226200, Jiangsu, China
| | - Xiaoyu Zhou
- Department of Gastroenterology, Affiliated Qidong Hospital of Nantong University, Qidong, 226200, Jiangsu, China
| | - Guohua Wang
- Institute of Special Environmental Medicine, Nantong University, Chongchuan District, 9 Seyuan Road, Nantong, 226019, Jiangsu, China.
| | - Weichang Chen
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
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2
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Nazari M, Babakhanzadeh E, Mollazadeh A, Ahmadzade M, Mohammadi Soleimani E, Hajimaqsoudi E. HOTAIR in cancer: diagnostic, prognostic, and therapeutic perspectives. Cancer Cell Int 2024; 24:415. [PMID: 39702144 DOI: 10.1186/s12935-024-03612-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 12/11/2024] [Indexed: 12/21/2024] Open
Abstract
The long non-coding RNA HOTAIR is overexpressed in many cancers and is associated with several cancer-promoting effects, including increased cell proliferation, migration and treatment resistance. HOTAIR levels correlate with tumor stage, lymph node metastasis and overall survival in patients with various types of cancer. This highlights the potential uses of HOTAIR, including early cancer detection, predicting patient outcome, identifying high-risk individuals and assisting in therapy selection and monitoring. The aim of this review is to provide a comprehensive summary of the research progress, molecular mechanisms and clinical significance of HOTAIR in various human cancers. In addition, the clinical applications of HOTAIR, such as targeted therapy, radiotherapy, chemotherapy and immunotherapy, are discussed, and relevant information on the potential future advances of HOTAIR in cancer research is provided.
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Affiliation(s)
- Majid Nazari
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, P.O. Box 64155-65117, Tehran, Yazd, Iran.
| | - Emad Babakhanzadeh
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arghavan Mollazadeh
- Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL, 60115, USA
| | - Mohadese Ahmadzade
- Department of Urology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Elnaz Hajimaqsoudi
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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3
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Luo S, Yue M, Wang D, Lu Y, Wu Q, Jiang J. Breaking the barrier: Epigenetic strategies to combat platinum resistance in colorectal cancer. Drug Resist Updat 2024; 77:101152. [PMID: 39369466 DOI: 10.1016/j.drup.2024.101152] [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: 05/22/2024] [Revised: 08/22/2024] [Accepted: 09/20/2024] [Indexed: 10/08/2024]
Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Platinum-based drugs, such as cisplatin and oxaliplatin, are frontline chemotherapy for CRC, effective in both monotherapy and combination regimens. However, the clinical efficacy of these treatments is often undermined by the development of drug resistance, a significant obstacle in cancer therapy. In recent years, epigenetic alterations have been recognized as key players in the acquisition of resistance to platinum drugs. Targeting these dysregulated epigenetic mechanisms with small molecules represents a promising therapeutic strategy. This review explores the complex relationship between epigenetic changes and platinum resistance in CRC, highlighting current epigenetic therapies and their effectiveness in countering resistance mechanisms. By elucidating the epigenetic underpinnings of platinum resistance, this review aims to contribute to ongoing efforts to improve treatment outcomes for CRC patients.
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Affiliation(s)
- Shiwen Luo
- Institute of Infection, Immunology and Tumor Microenvironment, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
| | - Ming Yue
- Department of Pharmacy, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China
| | - Dequan Wang
- Institute of Infection, Immunology and Tumor Microenvironment, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
| | - Yukang Lu
- Institute of Infection, Immunology and Tumor Microenvironment, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
| | - Qingming Wu
- Institute of Infection, Immunology and Tumor Microenvironment, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China; Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan 430065, China.
| | - Jue Jiang
- Institute of Infection, Immunology and Tumor Microenvironment, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China.
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4
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Hamdy NM, Zaki MB, Rizk NI, Abdelmaksoud NM, Abd-Elmawla MA, Ismail RA, Abulsoud AI. Unraveling the ncRNA landscape that governs colorectal cancer: A roadmap to personalized therapeutics. Life Sci 2024; 354:122946. [PMID: 39122108 DOI: 10.1016/j.lfs.2024.122946] [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: 06/19/2024] [Revised: 07/23/2024] [Accepted: 08/04/2024] [Indexed: 08/12/2024]
Abstract
Colorectal cancer (CRC) being one of the most common malignancies, has a significant death rate, especially when detected at an advanced stage. In most cases, the fundamental aetiology of CRC remains unclear despite the identification of several environmental and intrinsic risk factors. Numerous investigations, particularly in the last ten years, have indicated the involvement of epigenetic variables in this type of cancer. The development, progression, and metastasis of CRC are influenced by long non-coding RNAs (lncRNAs), which are significant players in the epigenetic pathways. LncRNAs are implicated in diverse pathological processes in CRC, such as liver metastasis, epithelial to mesenchymal transition (EMT), inflammation, and chemo-/radioresistance. It has recently been determined that CRC cells and tissues exhibit dysregulation of tens of oncogenic and tumor suppressor lncRNAs. Serum samples from CRC patients exhibit dysregulated expressions of several of these transcripts, offering a non-invasive method of detecting this kind of cancer. In this review, we outlined the typical paradigms of the deregulated lncRNA which exert significant role in the underlying molecular mechanisms of CRC initiation and progression. We comprehensively discuss the role of lncRNAs as innovative targets for CRC prognosis and treatment.
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Affiliation(s)
- Nadia M Hamdy
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abbasia Cairo, 11566, Egypt.
| | - Mohamed Bakr Zaki
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Menoufia, 32897, Egypt
| | - Nehal I Rizk
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | | | - Mai A Abd-Elmawla
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Kasr Al Ainy, Cairo, 11562, Egypt
| | - Rehab A Ismail
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Ahmed I Abulsoud
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al Azhar University, Nasr City, Cairo, 11231, Egypt
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5
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Li P, Ma X, Huang D. Role of the lncRNA/Wnt signaling pathway in digestive system cancer: a literature review. Eur J Med Res 2024; 29:447. [PMID: 39218950 PMCID: PMC11367813 DOI: 10.1186/s40001-024-02033-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: 03/24/2024] [Accepted: 08/21/2024] [Indexed: 09/04/2024] Open
Abstract
The long noncoding RNA (lncRNA)/Wingless (Wnt) axis is often dysregulated in digestive system tumors impacting critical cellular processes. Abnormal expression of specific Wnt-related lncRNAs such as LINC01606 (promotes motility), SLCO4A1-AS1 (promotes motility), and SH3BP5-AS1 (induces chemoresistance), plays a crucial role in these malignancies. These lncRNAs are promising targets for cancer diagnosis and therapy, offering new treatment perspectives. The lncRNAs, NEF and GASL1, differentially expressed in plasma show diagnostic potential for esophageal squamous cell carcinoma and gastric cancer, respectively. Additionally, Wnt pathway inhibitors like XAV-939 have demonstrated preclinical efficacy, underscoring their therapeutic potential. This review comprehensively analyzes the lncRNA/Wnt axis, highlighting its impact on cell proliferation, motility, and chemoresistance. By elucidating the complex molecular mechanisms of the lncRNA/Wnt axis, we aim to identify potential therapeutic targets for digestive system tumors to pave the way for the development of targeted treatment strategies.
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Affiliation(s)
- Penghui Li
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471000, Henan, China.
| | - Xiao Ma
- Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Di Huang
- Department of Child Health Care, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
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6
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Cantile M, Belli V, Scognamiglio G, Martorana A, De Pietro G, Tracey M, Budillon A. The role of HOTAIR in the modulation of resistance to anticancer therapy. Front Mol Biosci 2024; 11:1414651. [PMID: 38887279 PMCID: PMC11181001 DOI: 10.3389/fmolb.2024.1414651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 05/10/2024] [Indexed: 06/20/2024] Open
Abstract
Leading anti-tumour therapeutic strategies typically involve surgery and radiotherapy for locally advanced (non-metastatic) cancers, while hormone therapy, chemotherapy, and molecular targeted therapy are the current treatment options for metastatic cancer. Despite the initially high sensitivity rate to anticancer therapies, a large number of patients develop resistance, leading to a poor prognosis. The mechanisms related to drug resistance are highly complex, and long non-coding RNAs appear to play a crucial role in these processes. Among these, the lncRNA homeobox transcript antisense intergenic RNA (HOTAIR), widely implicated in cancer initiation and progression, likewise plays a significant role in anticancer drug resistance. It can modulate cell activities such as proliferation, apoptosis, hypoxia, autophagy, as well as epithelial-mesenchymal transition, thereby contributing to the development of resistant tumour cells. In this manuscript, we describe different mechanisms of antitumor drug resistance in which HOTAIR is involved and suggest its potential as a therapeutic predictive biomarker for the management of cancer patients.
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Affiliation(s)
- Monica Cantile
- Scientific Directorate, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy
| | - Valentina Belli
- Scientific Directorate, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy
| | - Giosuè Scognamiglio
- Scientific Directorate, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy
| | - Anna Martorana
- Scientific Directorate, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy
| | - Giovanna De Pietro
- Scientific Directorate, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy
| | - Maura Tracey
- Rehabilitation Medicine Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy
| | - Alfredo Budillon
- Scientific Directorate, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy
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Abida, Imran M, Eltaib L, Ali A, Alanazi RAS, Singla N, Asdaq SMB, Al-Hajeili M, Alhakami FA, Al-Abdulhadi S, Abdulkhaliq AA, Rabaan AA. LncRNAs: Emerging biomarkers and therapeutic targets in rectal cancer. Pathol Res Pract 2024; 257:155294. [PMID: 38603843 DOI: 10.1016/j.prp.2024.155294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 04/03/2024] [Accepted: 04/04/2024] [Indexed: 04/13/2024]
Abstract
According to findings, long non-coding RNAs (lncRNAs) have an important function in the onset and growth of various cancers, including rectal cancer (RC). RC offers unique issues in terms of diagnosis, treatment, and results, needing a full understanding of the cellular mechanisms that cause it to develop. This thorough study digs into the various functions that lncRNAs perform in RC, giving views into their multiple roles as well as possible therapeutic consequences. The function of lncRNAs in RC cell proliferation, apoptosis, migratory and infiltrating capacities, epithelial-mesenchymal shift, and therapy tolerance are discussed. Various lncRNA regulatory roles are investigated in depth, yielding information on their effect on essential cell functions such as angiogenesis, death, immunity, and growth. Systemic lncRNAs are currently acknowledged as potential indications for the initial stages of identification of cancer, with the ability to diagnose as well as forecast. Besides adding to their diagnostic utility, lncRNAs offer therapeutic opportunities as actors, contributing to the expanding landscape of cancer research. Moreover, the investigation looks into the assessment and predictive utility of lncRNAs as RC markers. The article also offers insight into lncRNAs as chemoresistance and drug resistance facilitators in the setting of RC.
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Affiliation(s)
- Abida
- Department of Pharmaceutical Chemistry, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia
| | - Mohd Imran
- Department of Pharmaceutical Chemistry, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia.
| | - Lina Eltaib
- Department of Pharmaceutics, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia
| | - Akbar Ali
- Department of Pharmacy Practice, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia
| | | | - Neelam Singla
- School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Mahal Road, Jaipur 302017, India
| | | | - Marwan Al-Hajeili
- Department of Medicine, King Abdulaziz University, Jeddah 23624, Saudi Arabia
| | - Fatemah Abdulaziz Alhakami
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia
| | - Saleh Al-Abdulhadi
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Riyadh 11942, Saudi Arabia; Dr. Saleh Office for Medical Genetic and Genetic Counseling Services, The house of Expertise, Prince Sattam bin Abdulaziz University, Dammam 32411, Saudi Arabia
| | - Altaf A Abdulkhaliq
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | - Ali A Rabaan
- Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; Department of Public Health and Nutrition, The University of Haripur, Haripur 22610, Pakistan
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8
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Khalafizadeh A, Hashemizadegan SD, Shokri F, Bakhshinejad B, Jabbari K, Motavaf M, Babashah S. Competitive endogenous RNA networks: Decoding the role of long non-coding RNAs and circular RNAs in colorectal cancer chemoresistance. J Cell Mol Med 2024; 28:e18197. [PMID: 38506091 PMCID: PMC10951891 DOI: 10.1111/jcmm.18197] [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: 06/08/2023] [Revised: 11/17/2023] [Accepted: 02/04/2024] [Indexed: 03/21/2024] Open
Abstract
Colorectal cancer (CRC) is recognized as one of the most common gastrointestinal malignancies across the globe. Despite significant progress in designing novel treatments for CRC, there is a pressing need for more effective therapeutic approaches. Unfortunately, many patients undergoing chemotherapy develop drug resistance, posing a significant challenge for cancer treatment. Non-coding RNAs (ncRNAs) have been found to play crucial roles in CRC development and its response to chemotherapy. However, there are still gaps in our understanding of interactions among various ncRNAs, such as long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs). These ncRNAs can act as either oncogenes or tumour suppressors, affecting numerous biological functions in different cancers including CRC. A class of ncRNA molecules known as competitive endogenous RNAs (ceRNAs) has emerged as a key player in various cellular processes. These molecules form networks through lncRNA/miRNA/mRNA and circRNA/miRNA/mRNA interactions. In CRC, dysregulation of ceRNA networks has been observed across various cellular processes, including proliferation, apoptosis and angiogenesis. These dysregulations are believed to play a significant role in the progression of CRC and, in certain instances, may contribute to the development of chemoresistance. Enriching our knowledge of these dysregulations holds promise for advancing the field of diagnostic and therapeutic modalities for CRC. In this review, we discuss lncRNA- and circRNA-associated ceRNA networks implicated in the emergence and advancement of drug resistance in colorectal carcinogenesis.
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Affiliation(s)
- Ali Khalafizadeh
- Department of Molecular Genetics, Faculty of Biological SciencesTarbiat Modares UniversityTehranIran
| | | | - Fatemeh Shokri
- Research and Development Center of BiotechnologyTarbiat Modares UniversityTehranIran
| | - Babak Bakhshinejad
- Department of Molecular Genetics, Faculty of Biological SciencesTarbiat Modares UniversityTehranIran
| | - Keyvan Jabbari
- Department of Molecular Genetics, Faculty of Biological SciencesTarbiat Modares UniversityTehranIran
| | - Mahsa Motavaf
- Department of Molecular Genetics, Faculty of Biological SciencesTarbiat Modares UniversityTehranIran
| | - Sadegh Babashah
- Department of Molecular Genetics, Faculty of Biological SciencesTarbiat Modares UniversityTehranIran
- Research and Development Center of BiotechnologyTarbiat Modares UniversityTehranIran
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9
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Biswal P, Lalruatfela A, Behera SK, Biswal S, Mallick B. miR-203a-A multifaceted regulator modulating cancer hallmarks and therapy response. IUBMB Life 2024; 76:108-124. [PMID: 37792370 DOI: 10.1002/iub.2786] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 09/05/2023] [Indexed: 10/05/2023]
Abstract
MicroRNAs (miRNAs) are a class of noncoding RNAs of about 19-25 nucleotides, which serve as critical modulators of various cellular and biological processes by target gene regulation. Dysregulated expression of miRNAs modulates the pathophysiology of various human diseases, including cancer. Among miRNAs, miR-203a is one of the most extensively researched dysregulated miRNAs in different cancers. Our review investigated the roles of miR-203a in the hallmarks of cancer modulating different pathways through target gene regulations, chemoresistance, its crosstalk with other ncRNAs or genes in terms of ceRNAs impacting oncogenesis, and its potential applications in the diagnosis, prognosis, and chemotherapeutic responses in different cancer types. miR-203a impacts cancer cell behavior by regulating these exclusive hallmarks- sustaining proliferation, cell growth, invasion and metastasis, cell death, and angiogenesis. Besides, miR-203a is found in human circulating biofluids like plasma or serum of colorectal cancer, cervical cancer, and hepatocellular carcinoma, hinting at its potential as a biomarker. Further, miR-203a is involved in enhancing the chemosensitivity of cisplatin, docetaxel, paclitaxel, doxorubicin, and 5-fluorouracil in a variety of malignancies through their cognate target genes. These results suggest that miR-203a is a crucial multifaceted miRNA that controls cancer cell proliferation, metastasis, and chemotherapy response, shedding new light on its possible application.
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Affiliation(s)
- Priyajit Biswal
- RNAi and Functional Genomics Lab., Department of Life Science, National Institute of Technology, Rourkela, Odisha, India
| | - Anthony Lalruatfela
- RNAi and Functional Genomics Lab., Department of Life Science, National Institute of Technology, Rourkela, Odisha, India
| | - Subham Kumar Behera
- RNAi and Functional Genomics Lab., Department of Life Science, National Institute of Technology, Rourkela, Odisha, India
| | - Sruti Biswal
- RNAi and Functional Genomics Lab., Department of Life Science, National Institute of Technology, Rourkela, Odisha, India
| | - Bibekanand Mallick
- RNAi and Functional Genomics Lab., Department of Life Science, National Institute of Technology, Rourkela, Odisha, India
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10
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Zhuo L, Hu Z, Chang J, Guo Q, Guo J. MicroRNA‑203a‑3p improves bleomycin and pingyangmycin sensitivity by inactivating the PI3K/AKT pathway in hemangioma. Exp Ther Med 2024; 27:80. [PMID: 38274341 PMCID: PMC10809328 DOI: 10.3892/etm.2024.12369] [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: 05/16/2023] [Accepted: 11/09/2023] [Indexed: 01/27/2024] Open
Abstract
MicroRNAs (miRs) have been found to play a fundamental role in the pathology and progression of hemangioma. Of note, miR-203a-3p prevents hemangioma progression via inactivation of the PI3K/AKT pathway. Bleomycin and pingyangmycin are drugs used in sclerotherapy, but certain hemangioma patients experience drug resistance, leading to poor clinical outcomes. The present study aimed to explore the impact of miR-203a-3p on bleomycin and pingyangmycin sensitivity in hemangioma, as well as the involvement of the PI3K/AKT pathway. miR-203a-3p or negative control mimics were transfected into human hemangioma endothelial cells, which were treated with 0-20 µM bleomycin or pingyangmycin. Subsequently, 740 Y-P, a PI3K/AKT pathway agonist, was added. Cell viability, rate of apoptosis and the expression levels of proteins involved in the PI3K/AKT pathway, including phosphorylated (p)-PI3K, PI3K, p-AKT and AKT, were detected. miR-203a-3p overexpression significantly decreased the half-maximal inhibitory concentration (IC50) values of bleomycin (5.84±0.87 vs. 14.23±2.17 µM; P<0.01) and pingyangmycin (5.13±0.55 vs. 12.04±1.86 µM; P<0.01), compared with untreated cells. In addition, under bleomycin or pingyangmycin treatment, miR-203a-3p overexpression significantly reduced the proportion of EdU positive cells (both P<0.05) and B-cell leukemia/lymphoma-2 (BCL2) protein expression levels (both P<0.05), whilst increasing cell apoptosis rate (both P<0.05) and cleaved caspase 3 protein expression levels (both P<0.05) compared with untreated controls. Furthermore, miR-203a-3p overexpression significantly inhibited the phosphorylation of PI3K and AKT (both P<0.05), an effect that was significantly diminished by 740 Y-P treatment (both P<0.01). In addition, 740 Y-P significantly increased IC50 values of bleomycin (P<0.01) and pingyangmycin (P<0.001) and also significantly increased the proportion of EdU-positive cells and BCL2 protein expression levels, while decreasing the apoptosis rate and cleaved caspase 3 protein expression levels in cells treated with bleomycin or pingyangmycin (all P<0.05). Of note, 740 Y-P weakened the effect of miR-203a-3p overexpression on the aforementioned cellular characteristics. The present study demonstrated that miR-203a-3p improved the sensitivity of cells to bleomycin and pingyangmycin treatment by inhibiting PI3K/AKT signaling in hemangioma.
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Affiliation(s)
- Lei Zhuo
- Department of General Surgery IV, (Department of Plastic Surgery), Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P.R. China
| | - Zhenfeng Hu
- Department of General Surgery II (Department of Plastic Surgery), Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P.R. China
| | - Jin Chang
- Department of General Surgery IV, (Department of Plastic Surgery), Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P.R. China
| | - Qing Guo
- The Fourth Wards of Department of Oncology, Handan Central Hospital, Handan, Hebei 056001, P.R. China
| | - Jing Guo
- The Fourth Wards of Department of Cardiovascular Medicine, Handan Central Hospital, Handan, Hebei 056001, P.R. China
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11
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Hakami MA, Hazazi A, Abdulaziz O, Almasoudi HH, Alhazmi AYM, Alkhalil SS, Alharthi NS, Alhuthali HM, Almalki WH, Gupta G, Khan FR. HOTAIR: A key regulator of the Wnt/β-catenin signaling cascade in cancer progression and treatment. Pathol Res Pract 2024; 253:154957. [PMID: 38000201 DOI: 10.1016/j.prp.2023.154957] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 11/12/2023] [Accepted: 11/15/2023] [Indexed: 11/26/2023]
Abstract
The long non-coding RNA (lncRNA) HOTAIR occupies a central position in the complex domain of cancer biology, particularly concerning its intricate interplay with the Wnt/β-catenin signaling pathway. This comprehensive review explores the multifaceted interactions between HOTAIR and the Wnt/β-catenin cascade, elucidating their profound function in cancer growth, progression, and therapeutic strategies. The study commences by underscoring the pivotal role of the Wnt/β-catenin cascade in governing essential cellular activities, emphasizing its dysregulation as a linchpin in cancer initiation and advancement. It introduces HOTAIR as a crucial regulatory entity, influencing gene expression in both healthy and diseased. The core of this review plunges into the intricacies of HOTAIR's engagement with Wnt/β-catenin signaling. It unravels how HOTAIR, through epigenetic modifications and transcriptional control, exerts its influence over key pathway constituents, including β-catenin, Wnt ligands, and target genes. This influence drives unchecked cancer cell growth, invasion, and metastasis. Furthermore, the review underscores the clinical significance of the HOTAIR-Wnt/β-catenin interplay, elucidating its associations with diverse cancer subtypes, patient prognoses, and prospects as a therapy. It provides insights into ongoing research endeavors to develop HOTAIR-targeted treatments and initiatives to facilitate aberrant Wnt/β-catenin activation. Concluding on a forward-looking note, the article accentuates the broader implications of HOTAIR's involvement in cancer biology, including its contributions to therapy resistance and metastatic dissemination. It underscores the importance of delving deeper into these intricate molecular relationships to pave the way for groundbreaking cancer treatment.
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Affiliation(s)
- Mohammed Ageeli Hakami
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Al-Quwayiyah, Shaqra University, Riyadh, Saudi Arabia
| | - Ali Hazazi
- Department of Pathology and Laboratory Medicine, Security Forces Hospital Program, Riyadh, Saudi Arabia
| | - Osama Abdulaziz
- Clinical Laboratory Sciences Department, College of Applied Medical Sciences, Taif University, Taif Province, Saudi Arabia
| | - Hassan Hussain Almasoudi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia
| | | | - Samia S Alkhalil
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Al-Quwayiyah, Shaqra University, Riyadh, Saudi Arabia
| | - Nahed S Alharthi
- Department of Medical Laboratory Sciences. College of Applied Medical Sciences in Al-Kharj, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudia Arabia
| | - Hayaa M Alhuthali
- Clinical Laboratory Sciences Department, College of Applied Medical Sciences, Taif University, Taif Province, Saudi Arabia
| | - Waleed Hassan Almalki
- Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Gaurav Gupta
- Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, India; School of Pharmacy, Graphic Era Hill University, Dehradun 248007, India; School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Mahal Road, Jaipur 302017, India
| | - Farhan R Khan
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Al-Quwayiyah, Shaqra University, Riyadh, Saudi Arabia.
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12
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Doghish AS, Zaki MB, Eldeib MG, Radwan AF, Moussa R, Abdel-Wahab MM, Kizilaslan EZ, Alhamshry NAA, Ashour AE, Elimam H. The potential relevance of long non-coding RNAs in colorectal cancer pathogenesis and treatment: A review focus on signaling pathways. Pathol Res Pract 2024; 253:155044. [PMID: 38141573 DOI: 10.1016/j.prp.2023.155044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 12/17/2023] [Accepted: 12/18/2023] [Indexed: 12/25/2023]
Abstract
Colorectal cancer (CRC) is one of the most frequent cancers in incidence and mortality. Despite advances in cancer biology, molecular genetics, and targeted treatments, CRC prognosis and survival have not kept pace. This is usually due to advanced staging and metastases at diagnosis. Thus, great importance has been placed upon understanding the molecular pathophysiology behind the development of CRC, which has highlighted the significance of non-coding RNA's role and associated intracellular signaling pathways in the pathogenesis of the disease. According to recent studies, long non-coding RNAs (lncRNA), a subtype of ncRNAs whose length exceeds 200 nucleotides, have been found to have regulatory functions on multiple levels. Their actions at the transcription, post-transcriptional, translational levels, and epigenetic regulation have made them prime modulators of gene expression. Due to their role in cellular cancer hallmarks, their dysregulation has been linked to several illnesses, including cancer. Furthermore, their clinical relevance has expanded due to their possible detection in blood which has cemented them as potential future biomarkers and thus, potential targets for new therapy. This review will highlight the importance of lncRNAs and related signaling pathways in the development of CRC and their subsequent clinical applications.
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Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Mohamed Bakr Zaki
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt
| | - Mahmoud Gomaa Eldeib
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Department of Biochemistry, Faculty of Pharmacy, Sinai University - Kantara Branch, 41636 Ismailia, Egypt
| | - Abdullah F Radwan
- Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo 11829, Egypt
| | - Rewan Moussa
- Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Maie M Abdel-Wahab
- Department of Biochemistry, Faculty of Pharmacy, Sinai University - Kantara Branch, 41636 Ismailia, Egypt
| | | | - Nora A A Alhamshry
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt
| | - Abdelkader E Ashour
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Salman International University, Ras Sudr, South Sinai, Egypt
| | - Hanan Elimam
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt.
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13
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Herrera-Orozco H, García-Castillo V, López-Urrutia E, Martinez-Gutierrez AD, Pérez-Yepez E, Millán-Catalán O, Cantú de León D, López-Camarillo C, Jacobo-Herrera NJ, Rodríguez-Dorantes M, Ramos-Payán R, Pérez-Plasencia C. Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet). Curr Issues Mol Biol 2023; 45:9549-9565. [PMID: 38132443 PMCID: PMC10742218 DOI: 10.3390/cimb45120597] [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: 10/20/2023] [Revised: 11/14/2023] [Accepted: 11/21/2023] [Indexed: 12/23/2023] Open
Abstract
Colorectal cancer (CRC) represents the second deadliest malignancy worldwide. Around 75% of CRC patients exhibit high levels of chromosome instability that result in the accumulation of somatic copy number alterations. These alterations are associated with the amplification of oncogenes and deletion of tumor-ppressor genes and contribute to the tumoral phenotype in different malignancies. Even though this relationship is well known, much remains to be investigated regarding the effect of said alterations in long non-coding RNAs (lncRNAs) and, in turn, the impact these alterations have on the tumor phenotype. The present study aimed to evaluate the role of differentially expressed lncRNAs coded in regions with copy number alterations in colorectal cancer patient samples. We downloaded RNA-seq files of the Colorectal Adenocarcinoma Project from the The Cancer Genome Atlas (TCGA) repository (285 sequenced tumor tissues and 41 non-tumor tissues), evaluated differential expression, and mapped them over genome sequencing data with regions presenting copy number alterations. We obtained 78 differentially expressed (LFC > 1|< -1, padj < 0.05) lncRNAs, 410 miRNAs, and 5028 mRNAs and constructed a competing endogenous RNA (ceRNA) network, predicting significant lncRNA-miRNA-mRNA interactions. Said network consisted of 30 lncRNAs, 19 miRNAs, and 77 mRNAs. To understand the role that our ceRNA network played, we performed KEGG and GO analysis and found several oncogenic and anti-oncogenic processes enriched by the molecular players in our network. Finally, to evaluate the clinical relevance of the lncRNA expression, we performed survival analysis and found that C5orf64, HOTAIR, and RRN3P3 correlated with overall patient survival. Our results showed that lncRNAs coded in regions affected by SCNAs form a complex gene regulatory network in CCR.
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Affiliation(s)
- Héctor Herrera-Orozco
- Laboratorio de Genómica, FES-Iztacala, Universidad Nacional Autónoma de México. Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Mexico; (H.H.-O.); (V.G.-C.); (E.L.-U.)
- Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Edificio D. Circuito de Posgrados, Ciudad Universitaria, Coyoacán, Mexico City 04510, Mexico
| | - Verónica García-Castillo
- Laboratorio de Genómica, FES-Iztacala, Universidad Nacional Autónoma de México. Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Mexico; (H.H.-O.); (V.G.-C.); (E.L.-U.)
| | - Eduardo López-Urrutia
- Laboratorio de Genómica, FES-Iztacala, Universidad Nacional Autónoma de México. Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Mexico; (H.H.-O.); (V.G.-C.); (E.L.-U.)
| | - Antonio Daniel Martinez-Gutierrez
- Laboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando 22, Tlalpan, Mexico City 14080, Mexico; (A.D.M.-G.); (E.P.-Y.); (O.M.-C.); (D.C.d.L.)
| | - Eloy Pérez-Yepez
- Laboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando 22, Tlalpan, Mexico City 14080, Mexico; (A.D.M.-G.); (E.P.-Y.); (O.M.-C.); (D.C.d.L.)
| | - Oliver Millán-Catalán
- Laboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando 22, Tlalpan, Mexico City 14080, Mexico; (A.D.M.-G.); (E.P.-Y.); (O.M.-C.); (D.C.d.L.)
| | - David Cantú de León
- Laboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando 22, Tlalpan, Mexico City 14080, Mexico; (A.D.M.-G.); (E.P.-Y.); (O.M.-C.); (D.C.d.L.)
| | - César López-Camarillo
- Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Calle Dr. García Diego 168, Cuauhtémoc, Mexico City 06720, Mexico;
| | - Nadia J. Jacobo-Herrera
- Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga 15, Tlalpan, Mexico City 14080, Mexico;
| | | | - Rosalío Ramos-Payán
- Faculty of Chemical and Biological Sciences, Autonomous University of Sinaloa, Culiacan 80030, Mexico;
| | - Carlos Pérez-Plasencia
- Laboratorio de Genómica, FES-Iztacala, Universidad Nacional Autónoma de México. Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Mexico; (H.H.-O.); (V.G.-C.); (E.L.-U.)
- Laboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando 22, Tlalpan, Mexico City 14080, Mexico; (A.D.M.-G.); (E.P.-Y.); (O.M.-C.); (D.C.d.L.)
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Tufail M. HOTAIR in colorectal cancer: structure, function, and therapeutic potential. Med Oncol 2023; 40:259. [PMID: 37530984 DOI: 10.1007/s12032-023-02131-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 07/19/2023] [Indexed: 08/03/2023]
Abstract
lncRNAs play a vital part in cancer development by regulating gene expression. Among these, the lncRNA HOTAIR has gained considerable attention due to its entanglement in multiple cellular processes, including chromatin remodeling and gene regulation. HOTAIR has a complex structure consisting of multiple domains that interact with various protein complexes and RNA molecules. In colorectal cancer (CRC), HOTAIR expression is upregulated, and its overexpression has been correlated with poor patient prognosis and resistance to chemotherapy. HOTAIR has been found to regulate gene expression and promote cancer growth by interacting with specific miRNAs. In addition, HOTAIR has been implicated in the development of treatment resistance in colorectal cancer. To develop effective treatments, it's important to understand how HOTAIR regulates gene expression. This article discusses HOTAIR's structure, functions, and mechanisms in CRC and its potential as a target for therapy. The author also suggests future research directions to better understand HOTAIR's role in CRC progression and drug resistance.
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Affiliation(s)
- Muhammad Tufail
- Institute of Biomedical Sciences, Shanxi University, Taiyuan, 030006, China.
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15
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Bhattacharjee R, Prabhakar N, Kumar L, Bhattacharjee A, Kar S, Malik S, Kumar D, Ruokolainen J, Negi A, Jha NK, Kesari KK. Crosstalk between long noncoding RNA and microRNA in Cancer. Cell Oncol (Dordr) 2023; 46:885-908. [PMID: 37245177 PMCID: PMC10356678 DOI: 10.1007/s13402-023-00806-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/26/2023] [Indexed: 05/29/2023] Open
Abstract
miRNAs and lncRNAs play a central role in cancer-associated gene regulations. The dysregulated expression of lncRNAs has been reported as a hallmark of cancer progression, acting as an independent prediction marker for an individual cancer patient. The interplay of miRNA and lncRNA decides the variation of tumorigenesis that could be mediated by acting as sponges for endogenous RNAs, regulating miRNA decay, mediating intra-chromosomal interactions, and modulating epigenetic components. This paper focuses on the influence of crosstalk between lncRNA and miRNA on cancer hallmarks such as epithelial-mesenchymal transition, hijacking cell death, metastasis, and invasion. Other cellular roles of crosstalks, such as neovascularization, vascular mimicry, and angiogenesis were also discussed. Additionally, we reviewed crosstalk mechanism with specific host immune responses and targeting interplay (between lncRNA and miRNA) in cancer diagnosis and management.
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Affiliation(s)
- Rahul Bhattacharjee
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT-DU), Bhubaneswar, Odisha, India
| | - Neeraj Prabhakar
- Centre for Structural System Biology, Department of Physics, University of Hamburg, c/o DESY, Building 15, Notkestr. 852267, Hamburg, Germany
- Pharmacy, Abo Akademi University, Tykistökatu 6A, Turku, Finland
| | - Lamha Kumar
- School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, India
| | - Arkadyuti Bhattacharjee
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT-DU), Bhubaneswar, Odisha, India
| | - Sulagna Kar
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT-DU), Bhubaneswar, Odisha, India
| | - Sumira Malik
- Amity Institute of Biotechnology, Amity University Jharkhand, Ranchi, Jharkhand, 834001, India
| | - Dhruv Kumar
- School of Health Sciences and Technology (SoHST), UPES University, Dehradun, Uttarakhand, India
| | - Janne Ruokolainen
- Department of Applied Physics, School of Science, Aalto University, Espoo, 00076, Finland
| | - Arvind Negi
- Department of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, Espoo, 00076, Finland.
| | - Niraj Kumar Jha
- Department of Biotechnology, School of Engineering and Technology (SET), Sharda University, Greater Noida, 201310, UP, India.
- School of Bioengineering & Biosciences, Lovely Professional University, Phagwara, 144411, India.
- Department of Biotechnology, School of Applied & Life Sciences (SALS), Uttaranchal University, Dehradun, 248007, India.
| | - Kavindra Kumar Kesari
- Department of Applied Physics, School of Science, Aalto University, Espoo, 00076, Finland.
- Faculty of Biological and Environmental Sciences, University of Helsinki, Biocentre 3, Helsinki, Finland.
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16
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Xiong B, Huang Q, Zheng H, Lin S, Xu J. Recent advances microRNAs and metabolic reprogramming in colorectal cancer research. Front Oncol 2023; 13:1165862. [PMID: 37576895 PMCID: PMC10415904 DOI: 10.3389/fonc.2023.1165862] [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: 02/16/2023] [Accepted: 06/07/2023] [Indexed: 08/15/2023] Open
Abstract
Colorectal cancer (CRC) is a cancer with the highest incidence and mortality. Alteration of gene expression is the main pathophysiological mechanism of CRC, which results in disturbed signaling pathways and cellular metabolic processes. MicroRNAs are involved in almost all pathophysiological processes and are correlative with colorectal cancer metabolism, proliferation, and chemotherapy resistance. Metabolic reprogramming, an important feature of cancer, is strongly correlative with the development and prognosis of cancers, including colorectal cancer. MicroRNAs can target enzymes involved in metabolic processes, thus playing a regulatory role in tumor metabolism. The disorder of the signaling pathway is another characteristic of tumor, which induces the occurrence and proliferation of tumors, and is closely correlative with the prognosis and chemotherapy resistance of tumor patients. MicroRNAs can target the components of the signaling pathways to regulate their transduction. Understanding the function of microRNAs in the occurrence and proliferation of CRC provides novel insights into the optimal treatment strategies, prognosis, and development of diagnosis in CRC. This article reviews the relationship between CRC and microRNA expression and hopes to provide new options for the diagnosis and treatment of CRC.
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Affiliation(s)
- Bin Xiong
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Qiaoyi Huang
- Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Huida Zheng
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Shu Lin
- Centre of Neurological and Metabolic Research, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
- Group of Neuroendocrinology, Garvan Institute of Medical Research, Sydney, NSW, Australia
| | - Jianhua Xu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
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17
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Ren Y, Liu Y, He W, Zhao W, Pan J, Gao H, Li Y, Zhang Y, Wang W. Expression of NEAT1 can be used as a predictor for Dex resistance in multiple myeloma patients. BMC Cancer 2023; 23:630. [PMID: 37407915 DOI: 10.1186/s12885-023-11084-x] [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: 12/26/2022] [Accepted: 06/17/2023] [Indexed: 07/07/2023] Open
Abstract
OBJECTIVE Multiple myeloma is a heterogeneous disorder and the intratumor genetic heterogeneity contributes to emergency of drug resistance. Dexamethasone has been used clinically for decades for MM. Nevertheless, their use is severely hampered by the risk of developing side effects and the occurrence of Dex resistance. LncRNA NEAT1 plays a oncogenic role and participates in drug resistance in many solid tumors. Therefore, we investigated a potential usefulness of this molecular as a biomarker for diagnosis of MM and possible correlations of NEAT1 expression with drug resistance and prognosis. METHODS Bone marrow and peripheral blood mononuclear cells samples were collected from 60 newly diagnosed MM patients. The expression of NEAT1expression level were detected by quantitative real-time PCR analyses. The relationship about the expression levels of lncRNA with other clinical and cytogenetic features was analyzed. In addition, we measured to analysis the correlation between the expression of NEAT1 and Dex resistance in MM patients. RESULTS It was found that the expression of NEAT1 is significantly higher in multiple myeloma patients compared to controls and does not change with other clinical features and cytogenetic features. We further discovered that overexpression of NEAT1 was associated with Dex resistance and a poor prognosis in MM patients. CONCLUSION LncRNA NEAT1 has a significant value that might act as a promoting factor in the development of MM and may be severed as a diagnostic factor in MM. NEAT1 invovled in Dex resistance, which provide a new interpretation during the chemotherapy for MM.
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Affiliation(s)
- Yuyue Ren
- The Second Affiliated Hospital of Harbin Medical University, No.246 Xuefu Street Nangang Block, 150081, Harbin, Heilongjiang Province, P.R. of China
| | - Yijun Liu
- Yanda Lu Daopei Hospital, Yanjiao Economic Development Zone, 101118, Sanhe, Langfang, Hebei Province, P.R. of China
| | - Wanting He
- The Second Affiliated Hospital of Harbin Medical University, No.246 Xuefu Street Nangang Block, 150081, Harbin, Heilongjiang Province, P.R. of China
| | - Weiwei Zhao
- The Second Affiliated Hospital of Harbin Medical University, No.246 Xuefu Street Nangang Block, 150081, Harbin, Heilongjiang Province, P.R. of China
| | - Jiaqi Pan
- The Second Affiliated Hospital of Harbin Medical University, No.246 Xuefu Street Nangang Block, 150081, Harbin, Heilongjiang Province, P.R. of China
| | - Haiyan Gao
- The Second Affiliated Hospital of Harbin Medical University, No.246 Xuefu Street Nangang Block, 150081, Harbin, Heilongjiang Province, P.R. of China
| | - Yuying Li
- The Second Affiliated Hospital of Harbin Medical University, No.246 Xuefu Street Nangang Block, 150081, Harbin, Heilongjiang Province, P.R. of China
| | - Ying Zhang
- The Second Affiliated Hospital of Harbin Medical University, No.246 Xuefu Street Nangang Block, 150081, Harbin, Heilongjiang Province, P.R. of China
| | - Wei Wang
- The Second Affiliated Hospital of Harbin Medical University, No.246 Xuefu Street Nangang Block, 150081, Harbin, Heilongjiang Province, P.R. of China.
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18
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He J, Wu W. Comprehensive landscape and future perspectives of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC): Based on a bibliometric analysis. Noncoding RNA Res 2023; 8:33-52. [PMID: 36311994 PMCID: PMC9582894 DOI: 10.1016/j.ncrna.2022.10.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 10/03/2022] [Accepted: 10/03/2022] [Indexed: 11/06/2022] Open
Abstract
This review aimed to use bibliometric analysis to sort out, analyze and summarize the knowledge foundation and hot topics in the field of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC), and point out future trends to inspire related research and innovation. We used CiteSpace to analyze publication outputs, countries, institutions, authors, journals, references, and keywords. Knowledge foundations, hotspots, and future trends were then depicted. The overall research showed the trend of biomedical-oriented multidisciplinary. Much evidence indicates that lncRNA plays the role of oncogene or tumor suppressor in the occurrence and development of CRC. Besides, many lncRNAs have multiple mechanisms. lncRNAs and metastasis of CRC, lncRNAs and drug resistance of CRC, and the clinical application of lncRNAs in CRC are current research hotspots. Through insight into the development trend of lncRNAs in CRC, this study will help researchers extract hidden valuable information for further research.
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Affiliation(s)
- Jia He
- Faculty Affairs and Human Resources Management Department, Southwest Medical University, Luzhou, China
| | - Wenhan Wu
- Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, China
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Yu Z, Tang H, Chen S, Xie Y, Shi L, Xia S, Jiang M, Li J, Chen D. Exosomal LOC85009 inhibits docetaxel resistance in lung adenocarcinoma through regulating ATG5-induced autophagy. Drug Resist Updat 2023; 67:100915. [PMID: 36641841 DOI: 10.1016/j.drup.2022.100915] [Citation(s) in RCA: 52] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/02/2022] [Accepted: 12/24/2022] [Indexed: 12/28/2022]
Abstract
AIMS This study aims at investigating the role of a neighbor long non-coding RNA (lncRNA) of HDAC4 (LOC85009) in docetaxel (DTX) resistance of lung adenocarcinoma (LUAD). METHODS RT-qPCR was used to analyze LOC85009 expression in DTX-resistant LUAD cells. In vitro and in vivo experiments were applied to detect the influence of LOC85009 on LUAD cell growth and xenograft tumor growth. DNA pull down assay, RNA pull down assay, ChIP assay, CoIP assay and RIP assay were performed to identify the direct interactions between factors. RESULTS LOC85009 was lowly-expressed in DTX-resistant LUAD cells. Functionally, LOC85009 overexpression inhibited DTX resistance and cell proliferation but triggered cell apoptosis. Moreover, we identified that LOC85009 was transferred from LUAD cells to DTX-resistant LUAD cells via exosomes. Exosomal LOC85009 inhibited DTX resistance, proliferation and autophagy while induced apoptosis in DTX-resistant cells. Additionally, we found that LOC85009 sequestered ubiquitin-specific proteinase 5 (USP5) to destabilize upstream transcription factor 1 (USF1) protein, thereby inactivating ATG5 transcription. CONCLUSIONS Exosomal LOC85009 inhibits DTX resistance through regulation of ATG5-induced autophagy via USP5/USF1 axis, suggesting that LOC85009 might be a potential target to reverse DTX resistance in the treatment of LUAD.
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Affiliation(s)
- Zhengyuan Yu
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, No.188 Shizi Street, Gusu District, Suzhou 215006, Jiangsu, China
| | - Hailin Tang
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510062, Guangdong, China
| | - Shaomu Chen
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, No.188 Shizi Street, Gusu District, Suzhou 215006, Jiangsu, China
| | - Yufeng Xie
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, No.188 Shizi Street, Gusu District, Suzhou 215006, Jiangsu, China
| | - Liyan Shi
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, No.188 Shizi Street, Gusu District, Suzhou 215006, Jiangsu, China
| | - Shuhua Xia
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, No.188 Shizi Street, Gusu District, Suzhou 215006, Jiangsu, China
| | - Min Jiang
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, No.188 Shizi Street, Gusu District, Suzhou 215006, Jiangsu, China.
| | - Jiaoyang Li
- Department of Ultrasound, Guangdong Provincial People's Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 519041, Guangdong, China.
| | - Dongqin Chen
- Department of Medical Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No.160 Pujian Road, Pudong New District, Shanghai, 200127, China; Department of Oncology, Nantong City No. 1 People's Hospital and Second Affiliated Hospital of Nantong University, No. 666, Shengli Road, Nantong 226000, Jiangsu Province, China.
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Li SY, Shi CJ, Fu WM, Zhang JF. Berberine inhibits tumour growth in vivo and in vitro through suppressing the lincROR-Wnt/β-catenin regulatory axis in colorectal cancer. J Pharm Pharmacol 2023; 75:129-138. [PMID: 36130331 DOI: 10.1093/jpp/rgac067] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 08/25/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND Berberine, a non-prescription medicine clinically applied for diarrhoea and gastroenteritis. Recent studies have demonstrated that it possesses anti-tumour properties in colorectal cancer, but the exact molecular mechanism remains obscure. OBJECTIVES To elucidate the underly molecular mechanisms of berberine in colorectal cancer from a perspective of epigenetics, and tried to explore the role of lincROR-Wnt/β-catenin molecular axis in the berberine induced the anti-tumour activity in colorectal cancer. METHODS The effects of berberine on cell growth, cell cycle and apoptosis were examined in CRC cells. The in vivo effect of berberine on tumour growth was investigated using a xenograft mice model. Moreover, lincROR and Wnt/β-catenin signalling were detected by luciferase activity, qRT-PCR and western blotting assays. KEY FINDINGS Berberine suppressed cell growth in vitro via inducing cell cycle arrest and apoptosis in CRC cell, and inhibited tumourigenesis in vivo. LincROR was significantly down-regulated by berberine, inducing the inactivation of the canonical Wnt/β-catenin signalling, meanwhile, the overexpression of lincROR partially reversed the suppressive effects on tumour growth and Wnt/β-catenin signalling induced by berberine. CONCLUSIONS Berberine inhibits tumour growth partially via regulating the lincROR-Wnt/β-catenin regulatory axis, which provides a strategy for the design of anti-tumour drugs for CRC patients after our advanced validation.
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Affiliation(s)
- Shi-Ying Li
- School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 511458, PR China
| | - Chuan-Jian Shi
- School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 511458, PR China
| | - Wei-Ming Fu
- School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 511458, PR China
| | - Jin-Fang Zhang
- Cancer center, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518000, PR China
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21
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Shenoy US, Adiga D, Gadicherla S, Kabekkodu SP, Hunter KD, Radhakrishnan R. HOX cluster-embedded lncRNAs and epithelial-mesenchymal transition in cancer: Molecular mechanisms and therapeutic opportunities. Biochim Biophys Acta Rev Cancer 2023; 1878:188840. [PMID: 36403923 DOI: 10.1016/j.bbcan.2022.188840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 11/05/2022] [Accepted: 11/13/2022] [Indexed: 11/18/2022]
Abstract
Although there has been substantial improvement in the treatment modalities, cancer remains the major cause of fatality worldwide. Metastasis, recurrence, and resistance to oncological therapies are the leading causes of cancer mortality. Epithelial-mesenchymal transition (EMT) is a complex biological process that allows cancer cells to undergo morphological transformation into a mesenchymal phenotype to acquire invasive potential. It encompasses reversible and dynamic ontogenesis by neoplastic cells during metastatic dissemination. Hence, understanding the molecular landscape of EMT is imperative to identify a reliable clinical biomarker to combat metastatic spread. Accumulating evidence reveals the role of HOX (homeobox) cluster-embedded long non-coding RNAs (lncRNAs) in EMT and cancer metastasis. They play a crucial role in the induction of EMT, modulating diverse biological targets. The present review emphasizes the involvement of HOX cluster-embedded lncRNAs in EMT as a molecular sponge, chromatin remodeler, signaling regulator, and immune system modulator. Furthermore, the molecular mechanisms behind therapy resistance and the potential use of novel drugs targeting HOX cluster-embedded lncRNAs in the clinical management of distant metastasis will be discussed.
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Affiliation(s)
- U Sangeetha Shenoy
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal- 576104, Karnataka, India
| | - Divya Adiga
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal- 576104, Karnataka, India
| | - Srikanth Gadicherla
- Deparment of Oral and Maxillofacial Surgery, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India
| | - Shama Prasada Kabekkodu
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal- 576104, Karnataka, India
| | - Keith D Hunter
- Liverpool Head and Neck Centre, Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | - Raghu Radhakrishnan
- Department of Oral Pathology, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India; Oral and Maxillofacial Pathology, School of Clinical Dentistry, The University of Sheffield, Sheffield, UK.
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22
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Beni FA, Kazemi M, Dianat-Moghadam H, Behjati M. MicroRNAs regulating Wnt signaling pathway in colorectal cancer: biological implications and clinical potentials. Funct Integr Genomics 2022; 22:1073-1088. [DOI: 10.1007/s10142-022-00908-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 10/06/2022] [Accepted: 10/07/2022] [Indexed: 11/09/2022]
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Han S, Cao Y, Guo T, Lin Q, Luo F. Targeting lncRNA/Wnt axis by flavonoids: A promising therapeutic approach for colorectal cancer. Phytother Res 2022; 36:4024-4040. [PMID: 36227024 DOI: 10.1002/ptr.7550] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 06/16/2022] [Accepted: 06/17/2022] [Indexed: 11/09/2022]
Abstract
Despite the dramatic advances in our understanding of the etiology of colorectal cancer (CRC) in recent decades, effective therapeutic strategies are still urgently needed. Oncogenic mutations in the Wnt/β-Catenin pathway are hallmarks of CRC. Moreover, long non-coding RNAs (lncRNAs) as molecular managers are involved in the initiation, progression, and metastasis of CRC. Therefore, it is important to further explore the interaction between lncRNAs and Wnt/β-Catenin signaling pathway for targeted therapy of CRC. Natural phytochemicals have not toxicity and can target carcinogenesis-related pathways. Growing evidences suggest that flavonoids are inversely associated with CRC risk. These bioactive compounds could target carcinogenesis pathways of CRC and reduced the side effects of anti-cancer drugs. The review systematically summarized the progress of flavonoids targeting lncRNA/Wnt axis in the investigations of CRC, which will provide a promising therapeutic approach for CRC and develop nutrition-oriented preventive strategies for CRC based on epigenetic mechanisms. In the field, more epidemiological and clinical trials are required in the future to verify feasibility of targeting lncRNA/Wnt axis by flavonoids in the therapy and prevention of CRC.
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Affiliation(s)
- Shuai Han
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, Hunan, People's Republic of China
| | - Yunyun Cao
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, Hunan, People's Republic of China
| | - Tianyi Guo
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, Hunan, People's Republic of China
| | - Qinlu Lin
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, Hunan, People's Republic of China
| | - Feijun Luo
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, Hunan, People's Republic of China
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24
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Eisa NH, Said E, Khodir AE, Sabry D, Ebrahim HA, Elsherbini DMA, Altemani R, Alnasser DM, Elsherbiny NM, El-Sherbiny M. Effect of Diacerein on HOTAIR/IL-6/STAT3, Wnt/β-Catenin and TLR-4/NF-κB/TNF-α axes in colon carcinogenesis. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2022; 95:103943. [PMID: 35934220 DOI: 10.1016/j.etap.2022.103943] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 08/02/2022] [Accepted: 08/03/2022] [Indexed: 06/15/2023]
Abstract
Colorectal cancer (CRC) is a common malignancy with high mortality and poor prognosis. Diacerein (DIA) is an anti-inflammatory used for treatment of osteoarthritis. We delineated some underlying molecular mechanisms of DIA's anti-carcinogenic effect in CRC using in vivo and in vitro models. Human Caco-2 cells were treated with DIA followed by MTT and Annexin V assays and CRC was experimentally induced using 1,2-dimethylhydrazine. DIA (50 mg/kg/day, orally) was administrated for 8 weeks. The MTT assay confirmed cytotoxic effect of DIA in vitro and Annexin V confirmed its apoptotic effect. DIA resulted in regression of tumour lesions with reduced colonic TLR4, NF-κB and TNF-α protein levels and down-regulated VEGF expression, confirming anti-angiogenic impact. DIA triggered caspase-3 expression and regulated Wnt/β-Catenin pathway, by apparently interrupting the IL-6/STAT3/ lncRNA HOTAIR axis. In conclusion, DIA disrupted IL-6/STAT3/ lncRNA HOTAIR axis which could offer an effective therapeutic strategy for the management of CRC.
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Affiliation(s)
- Nada H Eisa
- Biochemistry department, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt.
| | - Eman Said
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, New Mansoura University, New Mansoura 7723730, Egypt.
| | - Ahmed E Khodir
- Department of Pharmacology, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt
| | - Dina Sabry
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Badr University in Cairo, Badr City, Egypt; Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hasnaa Ali Ebrahim
- Department of Basic Medical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
| | - Dalia Mahmoud Abdelmonem Elsherbini
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, P.O.Box 2014, Sakaka, Saudi Arabia; Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Reem Altemani
- PharmD program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| | | | - Nehal M Elsherbiny
- Biochemistry department, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.
| | - Mohamed El-Sherbiny
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia.
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25
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Non-coding RNA network associated with obesity and rheumatoid arthritis. Immunobiology 2022; 227:152281. [DOI: 10.1016/j.imbio.2022.152281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 09/13/2022] [Indexed: 11/18/2022]
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26
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Kulkarni A, Gayathrinathan S, Nair S, Basu A, Al-Hilal TA, Roy S. Regulatory Roles of Noncoding RNAs in the Progression of Gastrointestinal Cancers and Health Disparities. Cells 2022; 11:2448. [PMID: 35954293 PMCID: PMC9367924 DOI: 10.3390/cells11152448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 07/31/2022] [Accepted: 08/03/2022] [Indexed: 01/17/2023] Open
Abstract
Annually, more than a million individuals are diagnosed with gastrointestinal (GI) cancers worldwide. With the advancements in radio- and chemotherapy and surgery, the survival rates for GI cancer patients have improved in recent years. However, the prognosis for advanced-stage GI cancers remains poor. Site-specific GI cancers share a few common risk factors; however, they are largely distinct in their etiologies and descriptive epidemiologic profiles. A large number of mutations or copy number changes associated with carcinogenesis are commonly found in noncoding DNA regions, which transcribe several noncoding RNAs (ncRNAs) that are implicated to regulate cancer initiation, metastasis, and drug resistance. In this review, we summarize the regulatory functions of ncRNAs in GI cancer development, progression, chemoresistance, and health disparities. We also highlight the potential roles of ncRNAs as therapeutic targets and biomarkers, mainly focusing on their ethnicity-/race-specific prognostic value, and discuss the prospects of genome-wide association studies (GWAS) to investigate the contribution of ncRNAs in GI tumorigenesis.
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Affiliation(s)
- Aditi Kulkarni
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA
- Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968, USA
| | - Sharan Gayathrinathan
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA
| | - Soumya Nair
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA
| | - Anamika Basu
- Copper Mountain College, Joshua Tree, CA 92252, USA
- Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA
| | - Taslim A. Al-Hilal
- Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968, USA
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Texas at El Paso, El Paso, TX 79968, USA
| | - Sourav Roy
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA
- Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968, USA
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27
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Matuszyk J. MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy. Mol Med 2022; 28:89. [PMID: 35922756 PMCID: PMC9351108 DOI: 10.1186/s10020-022-00516-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 07/22/2022] [Indexed: 12/12/2022] Open
Abstract
Background The active metabolite of 5-Fluorouracil (5FU), used in the treatment of several types of cancer, acts by inhibiting the thymidylate synthase encoded by the TYMS gene, which catalyzes the rate-limiting step in DNA replication. The major failure of 5FU-based cancer therapy is the development of drug resistance. High levels of TYMS-encoded protein in cancerous tissues are predictive of poor response to 5FU treatment. Expression of TYMS is regulated by various mechanisms, including involving non-coding RNAs, both miRNAs and long non-coding RNAs (lncRNAs). Aim To delineate the miRNAs and lncRNAs network regulating the level of TYMS-encoded protein. Main body Several miRNAs targeting TYMS mRNA have been identified in colon cancers, the levels of which can be regulated to varying degrees by lncRNAs. Due to their regulation by the MALAT1 lncRNA, these miRNAs can be divided into three groups: (1) miR-197-3p, miR-203a-3p, miR-375-3p which are downregulated by MALAT1 as confirmed experimentally and the levels of these miRNAs are actually reduced in colon and gastric cancers; (2) miR-140-3p, miR-330-3p that could potentially interact with MALAT1, but not yet supported by experimental results; (3) miR-192-5p, miR-215-5p whose seed sequences do not recognize complementary response elements within MALAT1. Considering the putative MALAT1-miRNAs interaction network, attention is drawn to the potential positive feedback loop causing increased expression of MALAT1 in colon cancer and hepatocellular carcinoma, where YAP1 acts as a transcriptional co-factor which, by binding to the TCF4 transcription factor/ β-catenin complex, may increase the activation of the MALAT1 gene whereas the MALAT1 lncRNA can inhibit miR-375-3p which in turn targets YAP1 mRNA. Conclusion The network of non-coding RNAs may reduce the sensitivity of cancer cells to 5FU treatment by upregulating the level of thymidylate synthase.
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Affiliation(s)
- Janusz Matuszyk
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 R. Weigla Street, 53-114, Wroclaw, Poland.
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28
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Xie W, Chu M, Song G, Zuo Z, Han Z, Chen C, Li Y, Wang ZW. Emerging roles of long noncoding RNAs in chemoresistance of pancreatic cancer. Semin Cancer Biol 2022; 83:303-318. [PMID: 33207266 DOI: 10.1016/j.semcancer.2020.11.004] [Citation(s) in RCA: 79] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/04/2020] [Accepted: 11/05/2020] [Indexed: 02/08/2023]
Abstract
Pancreatic cancer is one of the most common causes of cancer death in the world due to the lack of early symptoms, metastasis occurrence and chemoresistance. Therefore, early diagnosis by detection of biomarkers, blockade of metastasis, and overcoming chemoresistance are the effective strategies to improve the survival of pancreatic cancer patients. Accumulating evidence has revealed that long noncoding RNA (lncRNA) and circular RNAs (circRNAs) play essential roles in modulating chemosensitivity in pancreatic cancer. In this review article, we will summarize the role of lncRNAs in drug resistance of pancreatic cancer cells, including HOTTIP, HOTAIR, PVT1, linc-ROR, GAS5, UCA1, DYNC2H1-4, MEG3, TUG1, HOST2, HCP5, SLC7A11-AS1 and CASC2. We also highlight the function of circRNAs, such as circHIPK3 and circ_0000284, in regulation of drug sensitivity of pancreatic cancer cells. Moreover, we describe a number of compounds, including curcumin, genistein, resveratrol, quercetin, and salinomycin, which may modulate the expression of lncRNAs and enhance chemosensitivity in pancreatic cancers. Therefore, targeting specific lncRNAs and cicrRNAs could contribute to reverse chemoresistance of pancreatic cancer cells. We hope this review might stimulate the studies of lncRNAs and cicrRNAs, and develop the new therapeutic strategy via modulating these noncoding RNAs to promote chemosensitivity of pancreatic cancer cells.
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Affiliation(s)
- Wangkai Xie
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Man Chu
- Center of Scientific Research, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China
| | - Gendi Song
- Center of Scientific Research, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China
| | - Ziyi Zuo
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Zheng Han
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Chenbin Chen
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Yuyun Li
- Bengbu Medical College Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, School of Laboratory Medicine, Bengbu Medical College, Anhui, 233030, China.
| | - Zhi-Wei Wang
- Center of Scientific Research, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China.
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29
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Najafi S, Khatami SH, Khorsand M, Jamali Z, Shabaninejad Z, Moazamfard M, Majidpoor J, Aghaei Zarch SM, Movahedpour A. Long non-coding RNAs (lncRNAs); roles in tumorigenesis and potentials as biomarkers in cancer diagnosis. Exp Cell Res 2022; 418:113294. [PMID: 35870535 DOI: 10.1016/j.yexcr.2022.113294] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 07/11/2022] [Accepted: 07/16/2022] [Indexed: 12/15/2022]
Abstract
New research has indicated that long non-coding RNAs (lncRNAs) play critical roles in a broad range of biological processes, including the pathogenesis of many complex human diseases, including cancer. The detailed regulation mechanisms of many lncRNAs in cancer initiation and progression have yet to be discovered, even though a few of lncRNAs' functions in cancer have been characterized. In the present study, we summarize recent advances in the mechanisms and functions of lncRNAs in cancer. We focused on the roles of newly-identified lncRNAs as oncogenes and tumor suppressors, as well as the potential pathways these molecules could play. The paper also discusses their potential uses as biomarkers for the diagnosis and prognosis of cancer.
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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.
| | - Seyyed Hossein Khatami
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Marjan Khorsand
- Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zeinab Jamali
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Shabaninejad
- Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | | | - Jamal Majidpoor
- Department of Anatomy, Faculty of Medicine, Infectious Disease Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Seyed Mohsen Aghaei Zarch
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Zhao H, Ming T, Tang S, Ren S, Yang H, Liu M, Tao Q, Xu H. Wnt signaling in colorectal cancer: pathogenic role and therapeutic target. Mol Cancer 2022; 21:144. [PMID: 35836256 PMCID: PMC9281132 DOI: 10.1186/s12943-022-01616-7] [Citation(s) in RCA: 418] [Impact Index Per Article: 139.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 07/01/2022] [Indexed: 02/08/2023] Open
Abstract
Background The Wnt signaling pathway is a complex network of protein interactions that functions most commonly in embryonic development and cancer, but is also involved in normal physiological processes in adults. The canonical Wnt signaling pathway regulates cell pluripotency and determines the differentiation fate of cells during development. The canonical Wnt signaling pathway (also known as the Wnt/β-catenin signaling pathway) is a recognized driver of colon cancer and one of the most representative signaling pathways. As a functional effector molecule of Wnt signaling, the modification and degradation of β-catenin are key events in the Wnt signaling pathway and the development and progression of colon cancer. Therefore, the Wnt signaling pathway plays an important role in the pathogenesis of diseases, especially the pathogenesis of colorectal cancer (CRC). Objective Inhibit the Wnt signaling pathway to explore the therapeutic targets of colorectal cancer. Methods Based on studying the Wnt pathway, master the biochemical processes related to the Wnt pathway, and analyze the relevant targets when drugs or inhibitors act on the Wnt pathway, to clarify the medication ideas of drugs or inhibitors for the treatment of diseases, especially colorectal cancer. Results Wnt signaling pathways include: Wnt/β-catenin or canonical Wnt signaling pathway, planar cell polarity (Wnt-PCP) pathway and Wnt-Ca2+ signaling pathway. The Wnt signaling pathway is closely related to cancer cell proliferation, stemness, apoptosis, autophagy, metabolism, inflammation and immunization, microenvironment, resistance, ion channel, heterogeneity, EMT/migration/invasion/metastasis. Drugs/phytochemicals and molecular preparations for the Wnt pathway of CRC treatment have now been developed. Wnt inhibitors are also commonly used clinically for the treatment of CRC. Conclusion The development of drugs/phytochemicals and molecular inhibitors targeting the Wnt pathway can effectively treat colorectal cancer clinically.
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Affiliation(s)
- Hui Zhao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Tianqi Ming
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Shun Tang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Shan Ren
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Han Yang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Maolun Liu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Qiu Tao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Haibo Xu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
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Wang J, Zhao J, Hu P, Gao L, Tian S, He Z. Long Non-coding RNA HOTAIR in Central Nervous System Disorders: New Insights in Pathogenesis, Diagnosis, and Therapeutic Potential. Front Mol Neurosci 2022; 15:949095. [PMID: 35813070 PMCID: PMC9259972 DOI: 10.3389/fnmol.2022.949095] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 06/07/2022] [Indexed: 01/17/2023] Open
Abstract
Central nervous system (CNS) disorders, such as ischemic stroke, neurodegenerative diseases, multiple sclerosis, traumatic brain injury, and corresponding neuropathological changes, often lead to death or long-term disability. Long non-coding RNA (lncRNA) is a class of non-coding RNA with a transcription length over 200 nt and transcriptional regulation. lncRNA is extensively involved in physiological and pathological processes through epigenetic, transcription, and post-transcriptional regulation. Further, dysregulated lncRNA is closely related to the occurrence and development of human diseases, including CNS disorders. HOX Transcript antisense RNA (HOTAIR) is the first discovered lncRNA with trans-transcriptional regulation. Recent studies have shown that HOTAIR may participate in the regulation of the occurrence and development of CNS disorders. In addition, HOTAIR has the potential to become a new biomarker for the diagnosis and prognosis assessment of CNS disorders and even provide a new therapeutic target for CNS disorders. Here, we reviewed the research results of HOTAIR in CNS disorders to provide new insights into the pathogenesis, diagnostic value, and therapeutic target potential of HOTAIR in human CNS disorders.
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Affiliation(s)
- Jialu Wang
- Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jiuhan Zhao
- Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Pan Hu
- Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Lianbo Gao
- Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Shen Tian
- Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Zhenwei He
- Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
- *Correspondence: Zhenwei He,
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Qian X, Jiang C, Zhu Z, Han G, Xu N, Ye J, Wang R. Long non-coding RNA LINC00511 facilitates colon cancer development through regulating microRNA-625-5p to target WEE1. Cell Death Dis 2022; 8:233. [PMID: 35477702 PMCID: PMC9046421 DOI: 10.1038/s41420-021-00790-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 09/23/2021] [Accepted: 10/08/2021] [Indexed: 11/23/2022]
Abstract
The altered part of long non-coding RNA LINC00511 (LINC00511) is extensively discussed in malignancies. Finitely, the mechanism of LINC00511 in colon cancer (CC) development lacks thorough explorations. Hence, this work is started from the LINC00511-mediated microRNA (miR)-625-5p/WEE1 axis in the CC process. LINC00511, miR-625-5p, and WEE1 levels were tested in CC tissues and cells. Subcellular localization of LINC00511 was clarified. CC cells were transfected with oligonucleotides that altered LINC00511, and miR-625-5p expression to define their performance in CC cell progression. The tumorigenic ability of cells was verified in xenografted tumors. CC tissues and cells highly expressed LINC00511 and WEE1 and lowly expressed miR-625-5p. LINC00511 was mainly localized in the cytoplasm. Deleted LINC00511 or restored miR-625-5p delayed cellular growth in CC. LINC00511 sponged miR-625-5p to target WEE1. Silenced miR-625-5p mitigated the role of depleted LINC00511, while inhibited WEE1 rescued the effect of silenced miR-625-5p on the biological functions of CC cells. It is summarized that down-regulated LINC00511 obstructs tumorigenesis of CC through restoring miR-625-5p and silencing WEE1, consolidating a basal reference for CC-oriented therapy.
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Affiliation(s)
- Xiaowu Qian
- Department of Geriatrics, Taizhou People's Hospital (Taizhou People's Hospital affiliated to Nanjing Medical University), 225300, Taizhou, Jiangsu, China.
| | - Chun Jiang
- Department of Cardiology, Taizhou People's Hospital (Taizhou People's Hospital affiliated to Nanjing Medical University), 225300, Taizhou, Jiangsu, China
| | - Zhengtai Zhu
- Department of Geriatrics, Taizhou People's Hospital (Taizhou People's Hospital affiliated to Nanjing Medical University), 225300, Taizhou, Jiangsu, China
| | - Gaohua Han
- Department of Oncology, Taizhou People's Hospital (Taizhou People's Hospital affiliated to Nanjing Medical University), 225300, Taizhou, Jiangsu, China
| | - Ning Xu
- Department of Gastrointestinal Surgery, Taizhou People's Hospital (Taizhou People's Hospital affiliated to Nanjing Medical University), 225300, Taizhou, Jiangsu, China
| | - Jun Ye
- Department of Central Laboratory, Taizhou People's Hospital (Taizhou People's Hospital affiliated to Nanjing Medical University), Taizhou, 225300, Jiangsu, China
| | - Ruixing Wang
- Department of Geriatrics, Taizhou People's Hospital (Taizhou People's Hospital affiliated to Nanjing Medical University), 225300, Taizhou, Jiangsu, China
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33
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Abedi Kichi Z, Soltani M, Rezaei M, Shirvani-Farsani Z, Rojhannezhad M. The Emerging role of EMT-related lncRNAs in therapy resistance and their application as biomarkers. Curr Med Chem 2022; 29:4574-4601. [PMID: 35352644 DOI: 10.2174/0929867329666220329203032] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/15/2022] [Accepted: 01/19/2022] [Indexed: 12/09/2022]
Abstract
Cancer is the world's second largest cause of death. The most common cancer treatments are surgery, radiation therapy, and chemotherapy. Drug resistance, epithelial-to-mesenchymal transition (EMT), and metastasis are all pressing issues in cancer therapy today. Increasing evidence showed that drug-resistant and EMT are co-related with each other. Indeed, drug-resistant cancer cells possess enhanced EMT and invasive ability. Recent researches have demonstrated lncRNAs (long noncoding RNAs) are noncoding transcripts, which play an important role in the regulation of EMT, metastasis, and drug resistance in different cancers. However, the relationships among lncRNAs, EMT, and drug resistance are still unclear. These effects could be exerted via several signaling pathways such as TGF-β, PI3K-AKT, and Wnt/β-catenin. Identifying the crucial regulatory roles of lncRNAs in these pathways and processes leads to the development of novel targeted therapies. We review the key aspects of lncRNAs associated with EMT and therapy resistance. We focus on the crosstalk between lncRNAs and molecular signaling pathways affecting EMT and drug resistance. Moreover, each of the mentioned lncRNAs could be used as a potential diagnostic, prognostic, and therapeutic biomarker for cancer. Although, there are still many challenges to investigate lncRNAs for clinical applications.
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Affiliation(s)
- Zahra Abedi Kichi
- Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians University Munich, Germany
| | - Mona Soltani
- Department of Plant Production & Genetics, Faculty of Agriculture, Zanjan University, Zanjan, Iran
| | - Mina Rezaei
- Department of Cell and Molecular Biology, Faculty of life Sciences and Technology, Shahid Beheshti University, Tehran, IR Iran
| | - Zeinab Shirvani-Farsani
- Department of Cell and Molecular Biology, Faculty of life Sciences and Technology, Shahid Beheshti University, Tehran, IR Iran
| | - Mahbubeh Rojhannezhad
- Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, IR Iran
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de la Cruz-Ojeda P, Flores-Campos R, Navarro-Villarán E, Muntané J. The Role of Non-Coding RNAs in Autophagy During Carcinogenesis. Front Cell Dev Biol 2022; 10:799392. [PMID: 35309939 PMCID: PMC8926078 DOI: 10.3389/fcell.2022.799392] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 01/18/2022] [Indexed: 12/12/2022] Open
Abstract
Macroautophagy (autophagy herein) is a cellular stress response and a survival pathway involved in self-renewal and quality control processes to maintain cellular homeostasis. The alteration of autophagy has been implicated in numerous diseases such as cancer where it plays a dual role. Autophagy serves as a tumor suppressor in the early phases of cancer formation with the restoration of homeostasis and eliminating cellular altered constituents, yet in later phases, autophagy may support and/or facilitate tumor growth, metastasis and may contribute to treatment resistance. Key components of autophagy interact with either pro- and anti-apoptotic factors regulating the proximity of tumor cells to apoptotic cliff promoting cell survival. Autophagy is regulated by key cell signaling pathways such as Akt (protein kinase B, PKB), mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) involved in cell survival and metabolism. The expression of critical members of upstream cell signaling, as well as those directly involved in the autophagic and apoptotic machineries are regulated by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Consequently, non-coding RNAs play a relevant role in carcinogenesis and treatment response in cancer. The review is an update of the current knowledge in the regulation by miRNA and lncRNA of the autophagic components and their functional impact to provide an integrated and comprehensive regulatory network of autophagy in cancer.
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Affiliation(s)
- Patricia de la Cruz-Ojeda
- Institute of Biomedicine of Seville (IBiS), Hospital University "Virgen del Rocío"/CSIC/University of Seville, Seville, Spain.,Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain.,Networked Biomedical Research Center Hepatic and Digestive Diseases (CIBEREHD o Ciberehd), Institute of Health Carlos III, Madrid, Spain
| | - Rocío Flores-Campos
- Institute of Biomedicine of Seville (IBiS), Hospital University "Virgen del Rocío"/CSIC/University of Seville, Seville, Spain
| | - Elena Navarro-Villarán
- Institute of Biomedicine of Seville (IBiS), Hospital University "Virgen del Rocío"/CSIC/University of Seville, Seville, Spain.,Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain.,Networked Biomedical Research Center Hepatic and Digestive Diseases (CIBEREHD o Ciberehd), Institute of Health Carlos III, Madrid, Spain
| | - Jordi Muntané
- Institute of Biomedicine of Seville (IBiS), Hospital University "Virgen del Rocío"/CSIC/University of Seville, Seville, Spain.,Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain.,Networked Biomedical Research Center Hepatic and Digestive Diseases (CIBEREHD o Ciberehd), Institute of Health Carlos III, Madrid, Spain
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Olabayo Olatubosun M, Abubakar MB, Batiha GES, Malami I, Ibrahim KG, Abubakar B, Bello MB, Alexiou A, Imam MU. LncRNA SNHG15: A potential therapeutic target in the treatment of colorectal cancer. Chem Biol Drug Des 2022; 101:1138-1150. [PMID: 35191201 DOI: 10.1111/cbdd.14036] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 01/20/2022] [Accepted: 02/14/2022] [Indexed: 11/28/2022]
Abstract
The global burden of colorectal cancer (CRC) is increasing annually. CRC could develop from genetic and phenotypic factors involving changes in gene expression. Incredibly, the human genome transcribes into non-coding RNAs, among which long non-coding RNAs (lncRNAs) signify the most crucial part of the transcriptome in multicellular organisms. lncRNAs affect gene expression at multiple levels, from transcription to protein localization and stability. Recent studies have implicated lncRNA small nucleolar RNA host gene 15 (SNHG15) in cancers occurrence and progression. Previously, an indication suggests SNHG15 overexpression triggers proliferation, metastasis, and impedes apoptosis in CRC. Further, through its activity of binding micro-RNAs, lncRNA SNHG15 modulates genes associated with CRC progression and promotes CRC resistance to chemotherapeutic drugs. Here we reviewed recent findings on the various mechanisms and roles of lncRNA SNHG15 implicated in CRC tumorigenesis. We further highlight how SNHG15 plays a vital role in regulating critical pathways linked to the development and progression of CRC. Finally, we highlight how SNHG15 can be modulated for CRC treatments and the various therapeutic strategies to be implored when targeting SNHG15 in the context of CRC treatments. Findings from these studies present SNHG15 as a potential therapeutic target for preventing and treating CRC.
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Affiliation(s)
- Mutolib Olabayo Olatubosun
- Department of Biochemistry and Molecular Biology, Faculty of Sciences, Usmanu Danfodiyo University, P.M.B 2346, Sokoto, Nigeria.,Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria
| | - Murtala Bello Abubakar
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria.,Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, P.M.B, 2254, Sokoto, Nigeria
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt
| | - Ibrahim Malami
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria.,Department of Pharmacognosy and Ethnopharmacy, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, P.M.B 2346, Sokoto, Nigeria
| | - Kasimu Ghandi Ibrahim
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria.,Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, P.M.B, 2254, Sokoto, Nigeria
| | - Bilyaminu Abubakar
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria.,Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, P.M.B 2346, Sokoto, Nigeria
| | - Muhammad Bashir Bello
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria.,Department of Veterinary Microbiology, Faculty of Veterinary Medicine, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria
| | - Athanasios Alexiou
- Novel Global Community Educational Foundation, Hebersham, Australia.,AFNP Med Austria, Wien, Austria
| | - Mustapha Umar Imam
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria.,Department of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, P.M.B, 2254, Sokoto, Nigeria
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Nan S, Zhang S, Jin R, Wang J. LINC00665 up-regulates SIN3A expression to modulate the progression of colorectal cancer via sponging miR-138-5p. Cancer Cell Int 2022; 22:51. [PMID: 35101035 PMCID: PMC8802510 DOI: 10.1186/s12935-021-02176-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 08/24/2021] [Indexed: 12/13/2022] Open
Abstract
Background Colorectal cancer (CRC) is a malignant tumor affecting people worldwide. Long noncoding RNAs (lncRNAs) is a crucial factor modulating various cancer progression, including CRC. Long intergenic non-protein coding RNA 665 (LINC00665) has been proven as an oncogene in several cancers, but its function in CRC is still unclear. Methods QRT-PCR was performed for RNA quantification. Functional assays were designed and carried to test cell phenotype while mechanism experiments were adopted for detecting the interaction of LINC00665, microRNA-138-5p (miR-138-5p) and SIN3 transcription regulator family member A (SIN3A). In vivo experiments were conducted to test LINC00665 function on modulating CRC tumor progression. Results LINC00665 displayed high expression in CRC tissues and cells, and promoted tumor progression in vivo. MiR-138-5p displayed abnormally low expression in CRC, and was verified to be sponged by LINC00665. Furthermore, SIN3A, as the downstream mRNA of miR-138-5p, exerted promoting impacts on CRC cells. Rescue experiments certified that overexpressed SIN3A or silenced miR-138-5p could offset the repressed function of LINC00665 knockdown on CRC progression. Conclusions LINC00665 could sponge miR-138-5p to up-regulate SIN3A expression, thus accelerating CRC progression. Graphic abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s12935-021-02176-4.
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Affiliation(s)
- Shoushan Nan
- Department of Gastroenterology, Tianjin Fifth Center Hospital, No. 41 Zhejiang Road, Binhai New District, Tianjin, 300450, China.
| | - Shuangxia Zhang
- Department of Gastroenterology, Tianjin First Center Hospital, Tianjin, 300384, China
| | - Rong Jin
- Department of Gynaecology and Obstetrics, Tianjin Fifth Center Hospital, Tianjin, 300450, China
| | - Juelei Wang
- Department of Gastroenterology, Tianjin Fifth Center Hospital, No. 41 Zhejiang Road, Binhai New District, Tianjin, 300450, China
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Wu J, Tang X, Shi Y, Ma C, Zhang H, Zhang J, Lu Y, Wei J, Li L, Han L. Crosstalk of LncRNA HOTAIR and SP1-mediated repression of PDK1 contributes to β-Elemene-inhibited proliferation of hepatocellular carcinoma cells. JOURNAL OF ETHNOPHARMACOLOGY 2022; 283:114456. [PMID: 34333105 DOI: 10.1016/j.jep.2021.114456] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Revised: 07/15/2021] [Accepted: 07/24/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Hepatocellular carcinoma (HCC) is a liver malignancy which lacks effective treatment and has a poor prognosis. β-Elemene refers to a natural Curcuma wenyujin-derived single molecular entity, which exhibits various biological activities, and is especially well-known for it's antitumor properties. AIM OF THE RESEARCH LncRNA HOTAIR, SP1, and PDK1 have displayed oncogenic roles in many tumors, participating in the initiation and progression of cancers by mediating multiple signaling pathways. However, there are only a few reports about their roles and mutual relationship in the growth of HCC cells. Therefore, this study aimed to investigate the expression of LncRNA HOTAIR, SP1, and PDK1 and their interaction with β-Elemene in HCC cells. MATERIALS AND METHODS MTT, a Colony formation assay, and flow cytometry were employed to evaluate the growth of HCC and LO2 cells under β-Elemene. LncRNA HOTAIR, SP1 and PDK1 plasmids were transfected into HCC cells by a transient transfection assay, and the expression and interaction of LncRNA HOTAIR, SP1 and PDK1 were assessed via qRT-PCR and western blotting. RESULTS β-Elemene suppressed HCC cell growth through the downregulation of LncRNA HOTAIR, SP1 and PDK1. The results demonstrated a reciprocal interaction among LncRNA HOTAIR, SP1 and PDK1. Exogenous overexpression LncRNA HOTAIR or SP1 eliminated the suppressive effects of β-Elemene on them, and both of which regulated PDK1 expression in HCC cells. Additionally, exogenously overexpressed SP1 or LncRNA HOTAIR prevented β-Elemene inhibition of the protein-level expression of PDK1, whereas overexpressing PDK1 had no effect on SP1, though it still weakened the inhibition of cell growth and LncRNA HOTAIR expression by β-Elemene. CONCLUSION β-Elemene suppresses HCC cell proliferation via through the regulation of LncRNA HOTAIR, SP1, PDK1 and their interaction.
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Affiliation(s)
- JingJing Wu
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China.
| | - XiaoJuan Tang
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China
| | - Yao Shi
- Department of Cerebrovascular Disease, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China
| | - ChangJu Ma
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China
| | - Hongyu Zhang
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China
| | - Junhong Zhang
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China
| | - Yue Lu
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China
| | - Jianan Wei
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China
| | - Li Li
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China
| | - Ling Han
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou 510120, Guangdong, China; State key laboratory of Dampness Syndrome of Chinese Medicine, The second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China.
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Mammes A, Pasquier J, Mammes O, Conti M, Douard R, Loric S. Extracellular vesicles: General features and usefulness in diagnosis and therapeutic management of colorectal cancer. World J Gastrointest Oncol 2021; 13:1561-1598. [PMID: 34853637 PMCID: PMC8603448 DOI: 10.4251/wjgo.v13.i11.1561] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 06/29/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
In the world, among all type of cancers, colorectal cancer (CRC) is the third most commonly diagnosed in males and the second in females. In most of cases, (RP1) patients’ prognosis limitation with malignant tumors can be attributed to delayed diagnosis of the disease. Identification of patients with early-stage disease leads to more effective therapeutic interventions. Therefore, new screening methods and further innovative treatment approaches are mandatory as they may lead to an increase in progression-free and overall survival rates. For the last decade, the interest in extracellular vesicles (EVs) research has exponentially increased as EVs generation appears to be a universal feature of every cell that is strongly involved in many mechanisms of cell-cell communication either in physiological or pathological situations. EVs can cargo biomolecules, such as lipids, proteins, nucleic acids and generate transmission signal through the intercellular transfer of their content. By this mechanism, tumor cells can recruit and modify the adjacent and systemic microenvironment to support further invasion and dissemination. This review intends to cover the most recent literature on the role of EVs production in colorectal normal and cancer tissues. Specific attention is paid to the use of EVs for early CRC diagnosis, follow-up, and prognosis as EVs have come into the spotlight of research as a high potential source of ‘liquid biopsies’. The use of EVs as new targets or nanovectors as drug delivery systems for CRC therapy is also summarized.
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Affiliation(s)
- Aurelien Mammes
- INSERM UMR-938, Cancer Biology and Therapeutics Unit, Saint-Antoine Research Center, Saint Antoine University Hospital, Paris 75012, France
| | - Jennifer Pasquier
- INSERM UMR-938, Cancer Biology and Therapeutics Unit, Saint-Antoine Research Center, Saint Antoine University Hospital, Paris 75012, France
| | | | - Marc Conti
- INSERM UMR-938, Cancer Biology and Therapeutics Unit, Saint-Antoine Research Center, Saint Antoine University Hospital, Paris 75012, France
- Metabolism Research Unit, Integracell SAS, Longjumeau 91160, France
| | - Richard Douard
- UCBM, Necker University Hospital, Paris 75015, France
- Gastrointestinal Surgery Department, Clinique Bizet, Paris 75016, France
| | - Sylvain Loric
- INSERM UMR-938, Cancer Biology and Therapeutics Unit, Saint-Antoine Research Center, Saint Antoine University Hospital, Paris 75012, France
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Raei N, Safaralizadeh R, Hesseinpourfeizi M, Yazdanbod A, Pourfarzi F, Latifi-Navid S. Crosstalk between lncRNAs and miRNAs in gastrointestinal cancer drug resistance. Life Sci 2021; 284:119933. [PMID: 34508759 DOI: 10.1016/j.lfs.2021.119933] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 08/28/2021] [Accepted: 09/01/2021] [Indexed: 02/09/2023]
Abstract
Gastrointestinal cancers are one of the most prevalent malignancies worldwide. Dysregulation of lncRNAs by epigenetic alteration is crucial in gastrointestinal carcinogenesis. Epigenetic alteration includes DNA methylation, chromatin remodeling, histone modifications, and deregulated-gene expression by miRNAs. LncRNAs are involved in biological processes, including, uncontrolled cell division, migration, invasion, and resistance to apoptosis and drugs. Multiple-drug resistance (MDR) is a crucial obstacle in effective chemotherapy for gastrointestinal cancers. MDR can be associated with the prognosis and diagnosis of patients receiving chemotherapeutic agents (i.e. cisplatin, oxaliplatin, platinum, 5-fluorouracil, gefitinib, methotrexate, taxol, cetuximab, docetaxel, and gemcitabine). In this review, we focused on recently known lncRNAs and their relation with miRNAs and chemotherapeutic drugs, and their modulation in gastrointestinal cancers. Moreover, we mentioned the future prospective and clinical application of lncRNAs as a critical indicator and biomarker in diagnosis, prognosis, staging, grading, and treatment of gastrointestinal cancers.
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Affiliation(s)
- Negin Raei
- Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Reza Safaralizadeh
- Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
| | | | - Abbas Yazdanbod
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Farhad Pourfarzi
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran.
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Trujano-Camacho S, Cantú-de León D, Delgado-Waldo I, Coronel-Hernández J, Millan-Catalan O, Hernández-Sotelo D, López-Camarillo C, Pérez-Plasencia C, Campos-Parra AD. Inhibition of Wnt-β-Catenin Signaling by ICRT14 Drug Depends of Post-Transcriptional Regulation by HOTAIR in Human Cervical Cancer HeLa Cells. Front Oncol 2021; 11:729228. [PMID: 34778043 PMCID: PMC8580948 DOI: 10.3389/fonc.2021.729228] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 09/28/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND In Cervical cancer (CC), in addition to HPV infection, the most relevant alteration during CC initiation and progression is the aberrant activation of Wnt/β-catenin pathway. Several inhibitory drugs of this pathway are undergoing preclinical and clinical studies. Long non-coding RNAs (lncRNAs) are associated with resistance to treatments. In this regard, understanding the efficiency of drugs that block the Wnt/β-catenin pathway in CC is of relevance to eventually propose successful target therapies in patients with this disease. METHODS We analyzed the levels of expression of 249 components of the Wnt/β-catenin pathway in a group of 109 CC patients. Three drugs that blocking specific elements of Wnt/β-catenin pathway (C59, NSC668036 and ICRT14) by TOP FLASH assays and qRT-PCR were tested in vitro in CC cells. RESULTS 137 genes of the Wnt/β-catenin pathway were up-regulated and 112 down-regulated in CC patient's samples, demonstrating that this pathway is dysregulated. C59 was an efficient drug to inhibit Wnt/β-catenin pathway in CC cells. NSC668036, was not able to inhibit the transcriptional activity of the Wnt/β-catenin pathway. Strikingly, ICRT14 was neither able to inhibit this pathway in HeLa cells, due to HOTAIR interaction with β-catenin, maintaining the Wnt/β-catenin pathway activated. CONCLUSIONS These results demonstrate a mechanism by which HOTAIR evades the effect of ICRT14, a Wnt/β-catenin pathway inhibitory drug, in HeLa cell line. The emergence of these mechanisms reveals new scenarios in the design of target therapies used in cancer.
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Affiliation(s)
- Samuel Trujano-Camacho
- Postgraduate in Experimental Biology, DCBS, Autonomous Metropolitan University-Iztapalapa, Iztapalapa, Mexico
- Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Ciudad de México, Mexico
| | - David Cantú-de León
- Unidad de Investigaciones Biomédicas en Cancerología, Instituto Nacional de Cancerología (INCan), Ciudad de México, Mexico
| | - Izamary Delgado-Waldo
- Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Ciudad de México, Mexico
| | | | - Oliver Millan-Catalan
- Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Ciudad de México, Mexico
| | - Daniel Hernández-Sotelo
- Laboratorio de Epigenética del Cáncer, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo de los Bravo, Mexico
| | - César López-Camarillo
- Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Ciudad de México, Mexico
| | - Carlos Pérez-Plasencia
- Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Ciudad de México, Mexico
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México (UNAM), Tlalnepantla, Mexico
| | - Alma D. Campos-Parra
- Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Ciudad de México, Mexico
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Wang BQ, Wang JL, Zhang BQ, Li TT, Wang C, Sun GB. Prognostic role of HOTAIR in colorectal cancer: A meta-analysis. Shijie Huaren Xiaohua Zazhi 2021; 29:984-989. [DOI: 10.11569/wcjd.v29.i17.984] [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] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colorectal cancer is one of the most common malignant tumors. It is essential to find biomarkers for the early detection and evaluation of tumor prognosis. In recent years, studies have revealed that the expression of Hox transcription antisense RNA (HOTAIR) increases in various cancers, including colorectal cancer. However, due to the small sample size of each study, the persuasiveness is not strong.
AIM To perform a meta-analysis to explore the relationship between the expression of HOTAIR and the prognosis of colorectal cancer.
METHODS PubMed, MEDLINE, CNKI, CBM, and The Cochrane Library were searched for articles published before December 2020 on the relationship between HOTAIR expression and the prognosis of patients with colorectal cancer. Two reviewers independently evaluated the quality of the included articles and extracted the data. The risk ratio (HR) of overall survival (OS) and the odds ratio of lymph node metastasis (LNM) and distant metastasis (DM) were calculated to evaluate the association strength.
RESULTS Seven articles that met the inclusion criteria were included. Six of them compared the correlation between HOTAIR expression level and OS, and the results suggested that there existed a significant correlation between them (OR = 2.36, 95%CI: 1.74-3.19, P < 0.05). The correlation between HOTAIR expression level and LNM was compared in five articles, with a statistically significant correlation observed (OR = 4.07, 95%CI: 1.38-12.0, P < 0.05). Four articles compared the correlation between HOTAIR expression level and DM, and there was a statistically significant correlation between them (OR = 4.32, 95%CI: 1.60-11.62, P < 0.05).
CONCLUSION The high expression of HOTAIR in colorectal cancer is significantly correlated with decreased OS, LNM, and DM, which indicates that HOTAIR may be a new biomarker for evaluating the prognosis of colorectal cancer.
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Affiliation(s)
- Bai-Qing Wang
- The Fifth Central Hospital of Tianjin, Tianjin 300450, China
| | - Jue-Lei Wang
- The Fifth Central Hospital of Tianjin, Tianjin 300450, China
| | - Bao-Qin Zhang
- The Fifth Central Hospital of Tianjin, Tianjin 300450, China
| | - Tian-Tian Li
- The Fifth Central Hospital of Tianjin, Tianjin 300450, China
| | - Chao Wang
- The Fifth Central Hospital of Tianjin, Tianjin 300450, China
| | - Guang-Bin Sun
- The Fifth Central Hospital of Tianjin, Tianjin 300450, China
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Potential Roles of Exosomal lncRNAs in the Intestinal Mucosal Immune Barrier. J Immunol Res 2021; 2021:7183136. [PMID: 34485536 PMCID: PMC8413039 DOI: 10.1155/2021/7183136] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 08/15/2021] [Accepted: 08/17/2021] [Indexed: 12/31/2022] Open
Abstract
The intestinal mucosal immune barrier protects the host from the invasion of foreign pathogenic microorganisms. Immune cells and cytokines in the intestinal mucosa maintain local and systemic homeostasis by participating in natural and adaptive immunity. Deficiency of the intestinal mucosal immune barrier is associated with a variety of intestinal illnesses. Exosomes are phospholipid bilayer nanovesicles that allow cell-cell communication by secreting physiologically active substances including proteins, lipids, transcription factors, mRNAs, micro-RNAs (miRNAs), and long noncoding RNAs (lncRNAs). Exosomal lncRNAs are involved in immune cell differentiation and the modulation of the immune response. This review briefly introduces the potential role of exosomal lncRNAs in the intestinal mucosal immune barrier and discusses their relevance to intestinal illnesses.
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Huang L, Zhu L, Pan S, Xu J, Xie M, Wang W, Xia G. Circ_0029803 serves as the sponge of miR-216b-5p to promote the progression of colorectal cancer by regulating SKIL expression. World J Surg Oncol 2021; 19:268. [PMID: 34479589 PMCID: PMC8417978 DOI: 10.1186/s12957-021-02368-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 08/10/2021] [Indexed: 01/17/2023] Open
Abstract
Background Circular RNA 0029803 (circ_0029803) was found to be upregulated in colorectal cancer (CRC) tissues, but its function and underlying molecular mechanism are not studied in CRC. Methods The expression levels of circ_0029803, microRNA-216b-5p (miR-216b-5p), and ski-oncogene-like (SKIL) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). RNase R treatment was used to affirm the existence of circ_0029803. Cell proliferation, apoptosis, migration, and invasion were assessed by colony formation, flow cytometry, and Transwell assays, respectively. A glucose and lactate assay kit was used to detect glucose consumption and lactate production. Western blot was applied to analyze the levels of all proteins. Dual-luciferase reporter assay was performed to assess the relationship between miR-216b-5p and circ_0029803 or SKIL. Tumor xenograft models were established to elucidate the effect of circ_0029803 in vivo. Results Circ_0029803 expression was enhanced in CRC tissues and cells, and the 5-year overall survival rate of patients with high circ_0029803 expression was substantially reduced. Circ_0029803 depletion retarded proliferation, migration, invasion, EMT and glycolysis of CRC cells in vitro as well as the tumor growth in vivo. Mechanically, circ_0029803 could serve as miR-216b-5p sponge to regulate its expression, and miR-216b-5p knockdown reversed the inhibition of si-circ_0029803 on the malignant behaviors of CRC cells. Additionally, as the target mRNA of miR-216b-5p, SKIL could counteract the inhibitory effect of miR-216b-5p on the development of CRC cells. Importantly, silencing circ_0029803 reduced SKIL expression via sponging miR-216b-5p. Conclusion Circ_0029803 knockdown hindered proliferation, migration, invasion, EMT, and glycolysis and promoted apoptosis in CRC cells by modulating the miR-216b-5p/SKIL axis.
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Affiliation(s)
- Linfei Huang
- Department of Gastrointestinal Surgery, Wuhan Puren Hospital Affiliated to Wuhan University of Science and Technology, No.1 Benxi Street, Qingshan District, Wuhan City, 430080, Hubei Province, People's Republic of China
| | - Lei Zhu
- Department of Gastrointestinal Surgery, Wuhan Puren Hospital Affiliated to Wuhan University of Science and Technology, No.1 Benxi Street, Qingshan District, Wuhan City, 430080, Hubei Province, People's Republic of China
| | - Sheng Pan
- Department of Gastrointestinal Surgery, Wuhan Puren Hospital Affiliated to Wuhan University of Science and Technology, No.1 Benxi Street, Qingshan District, Wuhan City, 430080, Hubei Province, People's Republic of China
| | - Jing Xu
- Department of Gastrointestinal Surgery, Wuhan Puren Hospital Affiliated to Wuhan University of Science and Technology, No.1 Benxi Street, Qingshan District, Wuhan City, 430080, Hubei Province, People's Republic of China
| | - Miao Xie
- Department of Gastrointestinal Surgery, Wuhan Puren Hospital Affiliated to Wuhan University of Science and Technology, No.1 Benxi Street, Qingshan District, Wuhan City, 430080, Hubei Province, People's Republic of China
| | - Wei Wang
- Department of Gastrointestinal Surgery, Wuhan Puren Hospital Affiliated to Wuhan University of Science and Technology, No.1 Benxi Street, Qingshan District, Wuhan City, 430080, Hubei Province, People's Republic of China
| | - Ganlin Xia
- Department of Gastrointestinal Surgery, Wuhan Puren Hospital Affiliated to Wuhan University of Science and Technology, No.1 Benxi Street, Qingshan District, Wuhan City, 430080, Hubei Province, People's Republic of China.
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Huang Y, Wang L, Liu D. HOTAIR regulates colorectal cancer stem cell properties and promotes tumorigenicity by sponging miR-211-5p and modulating FLT-1. Cell Cycle 2021; 20:1999-2009. [PMID: 34470574 DOI: 10.1080/15384101.2021.1962636] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
We intended to investigate the underlying mechanism of action of long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in colorectal cancer (CRC) progression, especially in tumor cell stemness. For that purpose, different assays were performed such as real-time PCR and western blotting to determine the expression of target genes. Cell stemness was determined by sphere formation assay, flow cytometry assay, and the analysis of stemness-related markers. The interplay among target genes was evaluated using bioinformatics analyses, luciferase reporter and biotin-labeled RNA pull down assays. We found that HOTAIR was highly expressed and predicted poor prognosis survival in CRC. Downregulation of HOTAIR repressed tumor malignant behaviors and cancer stemness. Mechanistically, HOTAIR facilitated the expression of the microRNA (miR)-211-5p target gene fms-like tyrosine kinase-1 (FLT-1), thereby modulating cancer stem cell (CSC) properties in CRC. We conclude that HOTAIR/miR-211-5p/FLT-1 axis contributes to CRC cancer stemness.
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Affiliation(s)
- Ye Huang
- Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, P.R. China
| | - Liang Wang
- Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, P.R. China
| | - Di Liu
- Department of Anesthesiology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, P.R. China
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45
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Research updates on the clinical implication of long noncoding RNA in digestive system cancers and chemoresistance. 3 Biotech 2021; 11:423. [PMID: 34603923 DOI: 10.1007/s13205-021-02971-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Accepted: 08/19/2021] [Indexed: 10/20/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) are implicated in various biological processes, such as cell proliferation, differentiation, apoptosis, migration, and invasion. They are also key players in various biological pathways. LncRNA was considered as 'translational noise' before 1980s. It has been reported that lncRNAs are aberrantly expressed in different cancers, either as oncogene or tumor suppressor gene. Therefore, more and more lncRNAs are recognized as potential diagnostic biomarkers and/or therapeutic targets. As competitive endogenous RNA, lncRNAs can interact with microRNA to alter the expression of target genes, which may have extensive clinical implications in cancers, including diagnosis, treatment, prognosis, and chemoresistance. This review comprehensively summarizes the functions and clinical relevance of lncRNAs in digestive system cancers, especially as a potential tool to overcome chemoresistance.
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Jafarzadeh M, Soltani BM. MiRNA-Wnt signaling regulatory network in colorectal cancer. J Biochem Mol Toxicol 2021; 35:e22883. [PMID: 34382723 DOI: 10.1002/jbt.22883] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 08/02/2021] [Indexed: 01/05/2023]
Abstract
Colorectal cancer (CRC) is one of the common malignancies worldwide and the Wnt signaling pathway is recognized as the main disrupted pathway in this malignancy. MicroRNAs (miRNAs) are recognized to contribute to the pathogenesis of CRC by triggering or impeding the Wnt signaling pathway. In addition, transcriptional regulation of miRNAs by canonical Wnt signaling also participates in CRC cell progression. In this review, we present comprehensive literature of the existing data on the interaction of miRNAs and Wnt signaling that could be useful in future studies in the field of CRC management.
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Affiliation(s)
- Meisam Jafarzadeh
- Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Bahram M Soltani
- Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
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47
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Yao J, Wang C, Dong X, Zhang Y, Li Y, Zhou H, Zhang L. lncRNA SNHG22 sponges miR‑128‑3p to promote the progression of colorectal cancer by upregulating E2F3. Int J Oncol 2021; 59:71. [PMID: 34368861 PMCID: PMC8357263 DOI: 10.3892/ijo.2021.5251] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 06/14/2021] [Indexed: 12/24/2022] Open
Abstract
The long non‑coding RNA (lncRNA) small nucleolar RNA host gene 22 (SNHG22) has been reported as a crucial regulator in several types of human cancer. The present study evaluated the function and mechanism of SNHG22 in colorectal cancer (CRC) progression. SNHG22 expression was detected in colorectal adenoma, CRC tumor tissues (TTs) and adjacent non‑cancerous tissues (ANTs) using reverse transcription‑quantitative PCR (RT‑qPCR). The biological behaviors of SNHG22 in CRC cell lines were explored in vitro using Cell Counting Kit‑8, flow cytometry, wound scratch assay and Transwell assay, and in vivo using a nude mouse xenograft model. The interaction between SNHG22 and microRNA‑128‑3p (miR‑128‑3p), and the target genes of miR‑128‑3p were explored using online tools, RT‑qPCR, western blotting and a dual‑luciferase reporter assay. The present study revealed that SNHG22 expression was most highly expressed in TTs followed by adenoma tissues and ANTs. In addition, high SNHG22 expression levels were significantly associated with advanced clinicopathological factors and worse survival in patients with CRC. SNHG22 knockdown markedly inhibited CRC cell proliferation, apoptosis resistance, migration and invasion in vitro, and hindered tumor growth in vivo. The mechanistic study revealed that SNHG22 bound to miR‑128‑3p and attenuated its inhibitory effects on E2F transcription factor 3 (E2F3) expression levels and activity. Rescue experiments demonstrated that inhibiting miR‑128‑3p or upregulating E2F3 offset the effects of SNHG22 knockdown on CRC cells. The present findings support the existence of an interactive regulatory network involving SNHG22, miR‑128‑3p and E2F3 in CRC cell lines, indicating that the SNHG22/miR‑128‑3p/E2F3 axis may be considered a novel diagnostic and therapeutic target in CRC.
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Affiliation(s)
- Jianning Yao
- Department of Gastroenterology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Chunfeng Wang
- Department of Gastroenterology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Xuyang Dong
- Department of Gastroenterology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Yanzhen Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Yanle Li
- Department of Gastroenterology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Haining Zhou
- Department of Gastroenterology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Lianfeng Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
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48
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Yin H, Yu S, Xie Y, Dai X, Dong M, Sheng C, Hu J. Cancer-associated fibroblasts-derived exosomes upregulate microRNA-135b-5p to promote colorectal cancer cell growth and angiogenesis by inhibiting thioredoxin-interacting protein. Cell Signal 2021; 84:110029. [PMID: 33932496 DOI: 10.1016/j.cellsig.2021.110029] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/23/2021] [Accepted: 04/26/2021] [Indexed: 12/23/2022]
Abstract
OBJECTIVE The role of exosomes in human cancers has been identified, while the effect of cancer-associated fibroblasts (CAFs)-derived exosomes (CAF-exos) transmitting microRNAs (miRNAs) on colorectal cancer (CRC) remains largely unknown. We aim to explore the impact of CAF-derived exosomal miR-135b-5p on CRC progression by targeting thioredoxin-interacting protein (TXNIP). METHODS CRC tissues were collected to obtain CAF-exos, which were used to co-culture with LoVo and HT29 cells. The effect of miR-135b-5p and TXNIP on the in vivo growth, in vitro proliferation, apoptosis, migration, invasion and angiogenesis of CRC cells. miR-135b-5p and TXNIP expression in exosomes and CRC cells were detected and their targeting relationship was confirmed. RESULTS MiR-135b-5p was upregulated whereas TXNIP was downregulated in CRC tissues and cells. The CAF-exos and CAF-exos upregulating miR-135b-5p promoted in vivo growth, in vitro proliferation, migration and invasion, and suppressed apoptosis of CRC cells, and also promoted the HUVEC angiogenesis. TXNIP was confirmed as a target of miR-135b-5p and overexpression of TXNIP could weaken the pro-CRC effect of exosomal miR-135b-5p, CONCLUSION: CAF-exos upregulate miR-135b-5p to promote CRC cell growth and angiogenesis by inhibiting TXNIP.
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Affiliation(s)
- Hua Yin
- Ultrasonic diagnosis center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang, China; Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo 315000, Zhejiang, China; Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo 315000, Zhejiang, China
| | - Shanshan Yu
- Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang, China
| | - Yangyang Xie
- Endoscopy center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang, China
| | - Xiaoyu Dai
- Department of Anus & Intestine Sugery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang, China
| | - Mingjun Dong
- Department of Anus & Intestine Sugery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang, China
| | - Changrui Sheng
- Ultrasonic diagnosis center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang, China
| | - Jingjing Hu
- Ultrasonic diagnosis center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang, China.
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Xin X, Li Q, Fang J, Zhao T. LncRNA HOTAIR: A Potential Prognostic Factor and Therapeutic Target in Human Cancers. Front Oncol 2021; 11:679244. [PMID: 34367966 PMCID: PMC8340021 DOI: 10.3389/fonc.2021.679244] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 07/08/2021] [Indexed: 02/06/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of gene expression and physiological processes. LncRNAs are a class of ncRNAs of 200 nucleotides in length. HOX transcript antisense RNA (HOTAIR), a trans-acting lncRNA with regulatory function on transcription, can repress gene expression by recruiting chromatin modifiers. HOTAIR is an oncogenic lncRNA, and numerous studies have determined that HOTAIR is highly upregulated in a wide variety of human cancers. In this review, we briefly summarize the impact of lncRNA HOTAIR expression and functions on different human solid tumors, and emphasize the potential of HOTAIR on tumor prognosis and therapy. Here, we review the recent studies that highlight the prognostic potential of HOTAIR in drug resistance and survival, and the progress of therapies developed to target HOTAIR to date. Furthermore, targeting HOTAIR results in the suppression of HOTAIR expression or function. Thus, HOTAIR knockdown exhibits great therapeutic potential in various cancers, indicating that targeting lncRNA HOTAIR may serve as a promising strategy for cancer therapy. We also propose that preclinical studies involving HOTAIR are required to provide a better understanding of the exact molecular mechanisms underlying the dysregulation of its expression and function in different human cancers and to explore effective methods of targeting HOTAIR and engineering efficient and targeted drug delivery methods in vivo.
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Affiliation(s)
- Xiaoru Xin
- College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua, China
| | - Qianan Li
- College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua, China
| | - Jinyong Fang
- Department of Science and Education, Jinhua Guangfu Oncology Hospital, Jinhua, China
| | - Tiejun Zhao
- College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua, China
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50
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Ahadi A. Functional roles of lncRNAs in the pathogenesis and progression of cancer. Genes Dis 2021; 8:424-437. [PMID: 34179307 PMCID: PMC8209321 DOI: 10.1016/j.gendis.2020.04.009] [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: 03/12/2020] [Revised: 04/02/2020] [Accepted: 04/13/2020] [Indexed: 12/18/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) act as regulators of gene expression and pivotal transcriptional regulators in cancer cells via diverse mechanisms. lncRNAs involves a variety of pathological and biological activities, such as apoptosis, cell proliferation, metastasis, and invasion. By using microarray and RNA sequencing, it was identified that dysregulation of lncRNAs affects the tumorigenesis process. Taken together, these lncRNAs are putative biomarker and therapeutic target in human malignancies. In this review, I discuss the latest finding regarding the dysregulation of some important lncRNAs and their diverse mechanisms of these lncRNAs in the pathogenesis and progression of certain cancers; also, I summarize the possible roles of lncRNAs in clinical application for diagnosis and prognosis of cancer.
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Affiliation(s)
- Alireza Ahadi
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 198396-3113, Iran
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