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Kadian LK, Verma D, Lohani N, Yadav R, Ranga S, Gulshan G, Pal S, Kumari K, Chauhan SS. Long non-coding RNAs in cancer: multifaceted roles and potential targets for immunotherapy. Mol Cell Biochem 2024; 479:3229-3254. [PMID: 38413478 DOI: 10.1007/s11010-024-04933-1] [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: 06/06/2023] [Accepted: 01/05/2024] [Indexed: 02/29/2024]
Abstract
Cancer remains a major global health concern with high mortality rates mainly due to late diagnosis and poor prognosis. Long non-coding RNAs (lncRNAs) are emerging as key regulators of gene expression in human cancer, functioning through various mechanisms including as competing endogenous RNAs (ceRNAs) and indirectly regulating miRNA expression. LncRNAs have been found to have both oncogenic and tumor-suppressive roles in cancer, with the former promoting cancer cell proliferation, migration, invasion, and poor prognosis. Recent research has shown that lncRNAs are expressed in various immune cells and are involved in cancer cell immune escape and the modulation of the tumor microenvironment, thus highlighting their potential as targets for cancer immunotherapy. Targeting lncRNAs in cancer or immune cells could enhance the anti-tumor immune response and improve cancer immunotherapy outcomes. However, further research is required to fully understand the functional roles of lncRNAs in cancer and the immune system and their potential as targets for cancer immunotherapy. This review offers a comprehensive examination of the multifaceted roles of lncRNAs in human cancers, with a focus on their potential as targets for cancer immunotherapy. By exploring the intricate mechanisms underlying lncRNA-mediated regulation of cancer cell proliferation, invasion, and immune evasion, we provide insights into the diverse therapeutic applications of these molecules.
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Affiliation(s)
- Lokesh K Kadian
- Dept of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India
- Dept of Dermatology, Indiana University School of Medicine, Indianapolis, 46202, USA
| | - Deepika Verma
- Dept of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Neelam Lohani
- Dept of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Ritu Yadav
- Dept of Genetics, MD University, Rohtak, 124001, India
| | - Shalu Ranga
- Dept of Genetics, MD University, Rohtak, 124001, India
| | - Gulshan Gulshan
- Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, Maharashtra, India
| | - Sanghapriya Pal
- Dept of Biochemistry, Maulana Azad Medical College and Associated Hospital, New Delhi, 110002, India
| | - Kiran Kumari
- Dept of Forensic Science, Lovely Professional University, Jalandhar, Punjab, 144411, India
| | - Shyam S Chauhan
- Dept of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India.
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2
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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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3
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Rashwan HH, Taher AM, Hassan HA, Awaji AA, Kiriacos CJ, Assal RA, Youness RA. Harnessing the supremacy of MEG3 LncRNA to defeat gastrointestinal malignancies. Pathol Res Pract 2024; 256:155223. [PMID: 38452587 DOI: 10.1016/j.prp.2024.155223] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 02/16/2024] [Accepted: 02/21/2024] [Indexed: 03/09/2024]
Abstract
Evidence suggests that long non-coding RNAs (lncRNAs) play a pivotal role in the carcinogenesis and progression of various human malignancies including gastrointestinal malignancies. This comprehensive review reports the functions and mechanisms of the lncRNA maternally expressed gene 3 (MEG3) involved in gastrointestinal malignancies. It summarizes its roles in mediating the regulation of cellular proliferation, apoptosis, migration, invasiveness, epithelial-to-mesenchymal transition, and drug resistance in several gastrointestinal cancers such as colorectal cancer, gall bladder cancer, pancreatic cancer, gastric cancer, esophageal cancer, cholangiocarcinoma, gastrointestinal stromal tumors and most importantly, hepatocellular carcinoma. In addition, the authors briefly highlight its implicated mechanistic role and interactions with different non-coding RNAs and oncogenic signaling cascades. This review presents the rationale for developing non coding RNA-based anticancer therapy via harnessing the power of MEG3 in gastrointestinal malignancies.
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Affiliation(s)
- H H Rashwan
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt; Bioinformatics Group, Center for Informatics Science (CIS), School of Information Technology and Computer Science (ITCS), Nile University, 12677, Giza, Egypt
| | - A M Taher
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt
| | - H A Hassan
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt
| | - A A Awaji
- Department of Biology, Faculty of Science, University College of Taymaa, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - C J Kiriacos
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt
| | - R A Assal
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis University for Sustainable Development, Cairo, Egypt
| | - R A Youness
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt.
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4
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Saikia S, Postwala H, Athilingam VP, Anandan A, Padma VV, Kalita PP, Chorawala M, Prajapati B. Single Nucleotide Polymorphisms (SNPs) in the Shadows: Uncovering their Function in Non-Coding Region of Esophageal Cancer. Curr Pharm Biotechnol 2024; 25:1915-1938. [PMID: 38310451 DOI: 10.2174/0113892010265004231116092802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 10/02/2023] [Accepted: 10/04/2023] [Indexed: 02/05/2024]
Abstract
Esophageal cancer is a complex disease influenced by genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in non-coding regions of the genome have emerged as crucial contributors to esophageal cancer susceptibility. This review provides a comprehensive overview of the role of SNPs in non-coding regions and their association with esophageal cancer. The accumulation of SNPs in the genome has been implicated in esophageal cancer risk. Various studies have identified specific locations in the genome where SNPs are more likely to occur, suggesting a location-specific response. Chromatin conformational studies have shed light on the localization of SNPs and their impact on gene transcription, posttranscriptional modifications, gene expression regulation, and histone modification. Furthermore, miRNA-related SNPs have been found to play a significant role in esophageal squamous cell carcinoma (ESCC). These SNPs can affect miRNA binding sites, thereby altering target gene regulation and contributing to ESCC development. Additionally, the risk of ESCC has been linked to base excision repair, suggesting that SNPs in this pathway may influence disease susceptibility. Somatic DNA segment alterations and modified expression quantitative trait loci (eQTL) have also been associated with ESCC. These alterations can lead to disrupted gene expression and cellular processes, ultimately contributing to cancer development and progression. Moreover, SNPs have been found to be associated with the long non-coding RNA HOTAIR, which plays a crucial role in ESCC pathogenesis. This review concludes with a discussion of the current and future perspectives in the field of SNPs in non-coding regions and their relevance to esophageal cancer. Understanding the functional implications of these SNPs may lead to the identification of novel therapeutic targets and the development of personalized approaches for esophageal cancer prevention and treatment.
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Affiliation(s)
- Surovi Saikia
- Department of Natural Product Chemistry, Translational Research Laboratory, Bharathiar University, Coimbatore - 641 046, Tamil Nadu, India
| | - Humzah Postwala
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Ahmedabad, India
| | - Vishnu Prabhu Athilingam
- Department of Natural Product Chemistry, Translational Research Laboratory, Bharathiar University, Coimbatore - 641 046, Tamil Nadu, India
| | - Aparna Anandan
- Department of Natural Product Chemistry, Translational Research Laboratory, Bharathiar University, Coimbatore - 641 046, Tamil Nadu, India
| | - V Vijaya Padma
- Department of Natural Product Chemistry, Translational Research Laboratory, Bharathiar University, Coimbatore - 641 046, Tamil Nadu, India
| | - Partha P Kalita
- Program of Biotechnology, Assam Down Town University, Panikhaiti, Guwahati 781026, Assam, India
| | - Mehul Chorawala
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Ahmedabad, India
| | - Bhupendra Prajapati
- Department of Pharmaceutics and Pharmaceutical Technology, Shree. S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Kherva, Gujarat, India
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Zhang R, Gao X, Gu X. BBOX1-AS1: A novel oncogenic long non-coding RNA in human cancers. Pathol Res Pract 2023; 250:154810. [PMID: 37696243 DOI: 10.1016/j.prp.2023.154810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 09/08/2023] [Accepted: 09/08/2023] [Indexed: 09/13/2023]
Abstract
Long non-coding RNAs (lncRNAs) are transcripts that contain more than 200 nucleotides. Despite the fact that they cannot encode proteins, many studies have identified roles they play in human cancers through diverse mechanisms. BBOX1-AS1, an oncogenic lncRNA, has recently been demonstrated to participate in tumorigenesis and progression of numerous cancers. Experimental evidence has determined that it participates in diverse biological process, including cell proliferation, invasion, migration, and apoptosis. The dysregulation of BBOX1-AS1 exerts its oncogenicity by acting as a competitive endogenous RNA (ceRNA) or by directly impacting downstream molecules and signaling pathways. Here we summarize the current understanding of the biological functions and clinical significance of BBOX1-AS1 for human cancers.
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Affiliation(s)
- Renfang Zhang
- Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China
| | - Xiaohui Gao
- Department of Oncology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471000, Henan, China
| | - Xinyu Gu
- Department of Oncology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471000, Henan, China.
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Doghish AS, El-Husseiny AA, Abdelmaksoud NM, El-Mahdy HA, Elsakka EGE, Abdel Mageed SS, Mahmoud AMA, Raouf AA, Elballal MS, El-Dakroury WA, AbdelRazek MMM, Noshy M, El-Husseiny HM, Abulsoud AI. The interplay of signaling pathways and miRNAs in the pathogenesis and targeted therapy of esophageal cancer. Pathol Res Pract 2023; 246:154529. [PMID: 37196470 DOI: 10.1016/j.prp.2023.154529] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 05/06/2023] [Accepted: 05/08/2023] [Indexed: 05/19/2023]
Abstract
Globally, esophageal cancer (EC) is the 6th leading cause of cancer-related deaths and the second deadliest gastrointestinal cancer. Multiple genetic and epigenetic factors, such as microRNAs (miRNAs), influence its onset and progression. miRNAs are short nucleic acid molecules that can regulate multiple cellular processes by regulating gene expression. Therefore, EC initiation, progression, apoptosis evasions, invasion capacity, promotion, angiogenesis, and epithelial-mesenchymal transition (EMT) enhancement are associated with miRNA expression dysregulation. Wnt/-catenin signaling, Mammalian target of rapamycin (mTOR)/P-gp, phosphoinositide-3-kinase (PI3K)/AKT/c-Myc, epidermal growth factor receptor (EGFR), and transforming growth factor (TGF)-β signaling are crucial pathways in EC that are controlled by miRNAs. This review was conducted to provide an up-to-date assessment of the role of microRNAs in EC pathogenesis and their modulatory effects on responses to various EC treatment modalities.
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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.
| | - Ahmed A El-Husseiny
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City 11829, Cairo, Egypt
| | - Nourhan M Abdelmaksoud
- Department of Biochemistry and Biotechnology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Hesham A El-Mahdy
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Elsayed G E Elsakka
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Abdulla M A Mahmoud
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Ahmed Amr Raouf
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mohammed S Elballal
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Walaa A El-Dakroury
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mohamed M M AbdelRazek
- Department of Pharmacognosy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mina Noshy
- Clinical Pharmacy Department, Faculty of Pharmacy, King Salman International University (KSIU), SouthSinai, Ras Sudr 46612, Egypt
| | - Hussein M El-Husseiny
- Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi, Tokyo 183-8509, Japan; Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, Elqaliobiya 13736, Egypt
| | - Ahmed I Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Department of Biochemistry and Biotechnology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
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7
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Bai Z, Hu K, Yu J, Shen Y, Chen C. Macrophage migration inhibitory factor protects bone marrow mesenchymal stem cells from hypoxia/ischemia-induced apoptosis by regulating lncRNA MEG3. J Zhejiang Univ Sci B 2022; 23:989-1001. [PMID: 36518052 PMCID: PMC9758713 DOI: 10.1631/jzus.b2200110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 07/19/2022] [Indexed: 12/24/2022]
Abstract
OBJECTIVES This research was performed to explore the effect of macrophage migration inhibitory factor (MIF) on the apoptosis of bone marrow mesenchymal stem cells (BMSCs) in ischemia and hypoxia environments. METHODS The cell viability of BMSCs incubated under hypoxia/ischemia (H/I) conditions with or without pretreatment with MIF or triglycidyl isocyanurate (TGIC) was detected using cell counting kit-8 (CCK-8) analysis. Plasmids containing long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) or β-catenin small interfering RNA (siRNA) were used to overexpress or downregulate the corresponding gene, and the p53 signaling pathway was activated by pretreatment with TGIC. The influences of MIF, overexpression of lncRNA MEG3, activation of the p53 signaling pathway, and silencing of β-catenin on H/I-induced apoptosis of BMSCs were revealed by western blotting, flow cytometry, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining. RESULTS From the results of CCK-8 assay, western blotting, and flow cytometry, pretreatment with MIF significantly decreased the H/I-induced apoptosis of BMSCs. This effect was inhibited when lncRNA MEG3 was overexpressed by plasmids containing MEG3. The p53 signaling pathway was activated by TGIC, and β-catenin was silenced by siRNA. From western blot results, the expression levels of β-catenin in the nucleus and phosphorylated p53 (p-p53) were downregulated and upregulated, respectively, when the lncRNA MEG3 was overexpressed. Through flow cytometry, MIF was also shown to significantly alleviate the increased reactive oxygen species (ROS) level of BMSCs caused by H/I. CONCLUSIONS In summary, we conclude that MIF protected BMSCs from H/I-induced apoptosis by downregulating the lncRNA MEG3/p53 signaling pathway, activating the Wnt/β-catenin signaling pathway, and decreasing ROS levels.
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Affiliation(s)
- Zhibiao Bai
- First Clinical Medicine Institute, Wenzhou Medical University, Wenzhou 325006, China
- Department of Orthopaedics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325006, China
| | - Kai Hu
- First Clinical Medicine Institute, Wenzhou Medical University, Wenzhou 325006, China
| | - Jiahuan Yu
- First Clinical Medicine Institute, Wenzhou Medical University, Wenzhou 325006, China
| | - Yizhe Shen
- First Clinical Medicine Institute, Wenzhou Medical University, Wenzhou 325006, China
| | - Chun Chen
- First Clinical Medicine Institute, Wenzhou Medical University, Wenzhou 325006, China.
- Department of Orthopaedics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325006, China.
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Zhang L, Zhao F, Li W, Song G, Kasim V, Wu S. The Biological Roles and Molecular Mechanisms of Long Non-Coding RNA MEG3 in the Hallmarks of Cancer. Cancers (Basel) 2022; 14:cancers14246032. [PMID: 36551518 PMCID: PMC9775699 DOI: 10.3390/cancers14246032] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 12/06/2022] [Indexed: 12/13/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) are critical regulators in various biological processes involved in the hallmarks of cancer. Maternally expressed gene 3 (MEG3) is lncRNA that regulates target genes through transcription, translation, post-translational modification, and epigenetic regulation. MEG3 has been known as a tumor suppressor, and its downregulation could be found in various cancers. Furthermore, clinical studies revealed that impaired MEG3 expression is associated with poor prognosis and drug resistance. MEG3 exerts its tumor suppressive effect by suppressing various cancer hallmarks and preventing cells from acquiring cancer-specific characteristics; as it could suppress tumor cells proliferation, invasion, metastasis, and angiogenesis; it also could promote tumor cell death and regulate tumor cell metabolic reprogramming. Hence, MEG3 is a potential prognostic marker, and overexpressing MEG3 might become a potential antitumor therapeutic strategy. Herein, we summarize recent knowledge regarding the role of MEG3 in regulating tumor hallmarks as well as the underlying molecular mechanisms. Furthermore, we also discuss the clinical importance of MEG3, as well as their potential in tumor prognosis and antitumor therapeutic strategies.
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Affiliation(s)
- Lei Zhang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
- The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Fuqiang Zhao
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
- The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Wenfang Li
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Guanbin Song
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Vivi Kasim
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
- The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China
- Correspondence: (V.K.); (S.W.); Tel.: +86-23-65112672 (V.K.); +86-23-65111632 (S.W.); Fax: +86-23-65111802 (V.K. & S.W.)
| | - Shourong Wu
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
- The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China
- Correspondence: (V.K.); (S.W.); Tel.: +86-23-65112672 (V.K.); +86-23-65111632 (S.W.); Fax: +86-23-65111802 (V.K. & S.W.)
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Xu J, Wang X, Zhu C, Wang K. A review of current evidence about lncRNA MEG3: A tumor suppressor in multiple cancers. Front Cell Dev Biol 2022; 10:997633. [PMID: 36544907 PMCID: PMC9760833 DOI: 10.3389/fcell.2022.997633] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 11/22/2022] [Indexed: 12/12/2022] Open
Abstract
Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) is a lncRNA located at the DLK1-MEG3 site of human chromosome 14q32.3. The expression of MEG3 in various tumors is substantially lower than that in normal adjacent tissues, and deletion of MEG3 expression is involved in the occurrence of many tumors. The high expression of MEG3 could inhibit the occurrence and development of tumors through several mechanisms, which has become a research hotspot in recent years. As a member of tumor suppressor lncRNAs, MEG3 is expected to be a new target for tumor diagnosis and treatment. This review discusses the molecular mechanisms of MEG3 in different tumors and future challenges for the diagnosis and treatment of cancers through MEG3.
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Affiliation(s)
- Jie Xu
- Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xia Wang
- Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Chunming Zhu
- Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, China,*Correspondence: Chunming Zhu, ; Kefeng Wang,
| | - Kefeng Wang
- Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China,*Correspondence: Chunming Zhu, ; Kefeng Wang,
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Huang T, Wu Z, Zhu S. The roles and mechanisms of the lncRNA-miRNA axis in the progression of esophageal cancer: a narrative review. J Thorac Dis 2022; 14:4545-4559. [PMID: 36524088 PMCID: PMC9745524 DOI: 10.21037/jtd-22-1449] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 11/08/2022] [Indexed: 12/08/2023]
Abstract
BACKGROUND AND OBJECTIVE Esophageal cancer is one of the most common malignant digestive tract tumors. Despite various treatment methods, the prognosis of patients remains unsatisfactory, largely due to an insufficient understanding of the mechanisms involved in the pathogenesis and progression of esophageal cancer. More than 98% of the nucleotide sequences in the human genome do not encode proteins, and their transcription products are noncoding RNAs (ncRNAs), mainly long noncoding RNAs (lncRNAs) and microRNAs (miRNAs). Experiments have shown that lncRNAs and miRNAs play crucial roles in the occurrence and progression of various human malignancies. These ncRNAs influence the progression of esophageal cancer through an intricate regulatory network. We herein summarized the roles and mechanisms of the lncRNA-miRNA axis in esophageal cancer cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), invasion and metastasis, drug resistance, radiotherapy resistance, and angiogenesis. This review provides a rationale for anticancer therapy that targets the lncRNA-miRNA axis in esophageal cancer. METHODS Related articles published in the PubMed database between 05/30/2008 to 09/10/2022 were identified using the following terms: "lncRNA AND miRNA AND esophageal cancer", "lncRNA AND miRNA AND cell proliferation", "lncRNA AND miRNA AND apoptosis", "lncRNA AND miRNA AND EMT", "lncRNA AND miRNA AND invasion and metastasis", "lncRNA AND miRNA AND drug resistance", and "lncRNA AND miRNA AND radiotherapy resistance". Published articles written in English available to readers were considered. KEY CONTENT AND FINDINGS We summarized the roles of the lncRNA-miRNA axis in the progression of esophageal cancer, including cell proliferation, apoptosis, EMT, invasion and metastasis, drug resistance, radio resistance, and other progressions, and determined that the lncRNA-miRNA axis may serve as a potential clinical treatment target for esophageal cancer. CONCLUSIONS The lncRNA-miRNA axis is closely related to the progression of esophageal cancer and may act as a potential biological target for the clinical treatment of patients with esophageal cancer.
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Affiliation(s)
- Tao Huang
- Department of Thoracic Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, China
- Research Laboratory of Tumor Microenvironment, Wannan Medical College, Wuhu, China
| | - Zhihao Wu
- Research Laboratory of Tumor Microenvironment, Wannan Medical College, Wuhu, China
- School of Preclinical Medicine, Wannan Medical College, Wuhu, China
| | - Shaojin Zhu
- Department of Thoracic Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, China
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Bian S, Zhang X, Lin L, Sun L, Guo Z, Pan J, Cui J, Yao H, Xu J, Hao Z, Wang Y, Tong L, Bu X, Kong D, Liu N, Li Y. Exosomal MiR-4261 mediates calcium overload in RBCs by downregulating the expression of ATP2B4 in multiple myeloma. Front Oncol 2022; 12:978755. [PMID: 36091107 PMCID: PMC9458875 DOI: 10.3389/fonc.2022.978755] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 08/11/2022] [Indexed: 11/13/2022] Open
Abstract
Background Hypercalcemia induced by multiple myeloma (MM) affects the biological functions of excitable and non-excitable cells. However, red blood cells (RBCs) regulatory effect on calcium in hypercalcemia is still not fully understood. Methods A total of 113 patients with MM osteolytic lesions were studied retrospectively. Flow cytometry and atomic absorption spectroscopy were used to detect calcium content. Immunofluorescence and Western blotting were used to investigate protein expression. GEO and miRNA databases were used to screen miRNAs. Exosomal miR-4261 migration was investigated by Transwell assay. Dual-luciferase assays confirmed the targeting relationship between miR-4261 and ATP2B4. An RBC oxidative stress model was constructed, and Omega-Agatoxin IVA was used to study the role of plasma membrane Ca2+-ATPase 4 (PMCA4) in RBCs. Results The results showed that MM RBCs had calcium overload, and serum calcium levels increased as the number of RBCs decreased. The expression of PMCA4 in MM RBCs was significantly lower than in normal RBCs. The exosomal miR-4261 produced by MM cells could be transferred to RBCs to downregulate the expression of ATP2B4. Conclusions Studies have confirmed that RBCs experience calcium overload in MM with osteolytic lesions, which is related to the downregulation of ATP2B4 by MM exosomal miR-4261.
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Affiliation(s)
- Sicheng Bian
- Key Laboratory of Cell Transplantation of National Health Commission, Heilongjiang Key Laboratory of Blood and Hematopoietic System, Harbin Medical University, Harbin, China
- Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Xialin Zhang
- Department of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Leilei Lin
- Department of Hematology, Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
| | - Lili Sun
- Key Laboratory of Cell Transplantation of National Health Commission, Heilongjiang Key Laboratory of Blood and Hematopoietic System, Harbin Medical University, Harbin, China
- Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Zhibo Guo
- Key Laboratory of Cell Transplantation of National Health Commission, Heilongjiang Key Laboratory of Blood and Hematopoietic System, Harbin Medical University, Harbin, China
- Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Jie Pan
- Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, United States
| | - Jiangxia Cui
- Department of Hematology, Xi’an International Medical Center Hospital, Xi’an, China
| | - Hanbing Yao
- Department of Hematology, Xi’an International Medical Center Hospital, Xi’an, China
| | - Jing Xu
- Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Zhuanghui Hao
- Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Yuzhu Wang
- Key Laboratory of Cell Transplantation of National Health Commission, Heilongjiang Key Laboratory of Blood and Hematopoietic System, Harbin Medical University, Harbin, China
- Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Liguo Tong
- Central Laboratory, Shanxi Academy of Traditional Chinese Medicine, Taiyuan, China
| | - Xingpeng Bu
- Department of Geriatrics, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Desheng Kong
- Key Laboratory of Cell Transplantation of National Health Commission, Heilongjiang Key Laboratory of Blood and Hematopoietic System, Harbin Medical University, Harbin, China
| | - Nianjiao Liu
- Key Laboratory of Cell Transplantation of National Health Commission, Heilongjiang Key Laboratory of Blood and Hematopoietic System, Harbin Medical University, Harbin, China
| | - Yinghua Li
- Key Laboratory of Cell Transplantation of National Health Commission, Heilongjiang Key Laboratory of Blood and Hematopoietic System, Harbin Medical University, Harbin, China
- Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
- *Correspondence: Yinghua Li,
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Yu J, Zhu D, Zeng C, Zhang Y, Yang H, Xu Y. MicroRNA expression profiles in the granulosa cells of infertile patients undergoing progestin primed ovarian stimulation. Eur J Obstet Gynecol Reprod Biol 2022; 276:228-235. [DOI: 10.1016/j.ejogrb.2022.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 05/31/2022] [Accepted: 08/02/2022] [Indexed: 11/04/2022]
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Han Y, Zhao G, Shi X, Wang Y, Wen X, Zhang L, Guo X. The Emerging Role of Long Non-Coding RNAs in Esophageal Cancer: Functions in Tumorigenesis and Clinical Implications. Front Pharmacol 2022; 13:885075. [PMID: 35645836 PMCID: PMC9137892 DOI: 10.3389/fphar.2022.885075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 04/12/2022] [Indexed: 11/17/2022] Open
Abstract
Esophageal cancer (EC) is one of the most common malignancies of digestive tracts with poor five-year survival rate. Hence, it is very significant to further investigate the occurrence and development mechanism of esophageal cancer, find more effective biomarkers and promote early diagnosis and effective treatment. Long non-coding RNAs (lncRNAs) are generally defined as non-protein-coding RNAs with more than 200 nucleotides in length. Existing researches have shown that lncRNAs could act as sponges, guides, scaffolds, and signal molecules to influence the oncogene or tumor suppressor expressions at transcriptional, post-transcriptional, and protein levels in crucial cellular processes. Currently, the dysregulated lncRNAs are reported to involve in the pathogenesis and progression of EC. Importantly, targeting EC-related lncRNAs through genome editing, RNA interference and molecule drugs may be one of the most potential therapeutic methods for the future EC treatment. In this review, we summarized the biological functions and molecular mechanisms of lncRNAs, including oncogenic lncRNAs and tumor suppressor lncRNAs in EC. In addition, we generalized the excellent potential lncRNA candidates for diagnosis, prognosis and therapy in EC. Finally, we discussed the current challenges and opportunities of lncRNAs for EC.
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Affiliation(s)
- Yali Han
- Departments of Physiology, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Guo Zhao
- Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Xinhang Shi
- Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Yushan Wang
- Departments of Physiology, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Xin Wen
- Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Lu Zhang
- Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
| | - Xiangqian Guo
- Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Academy for Advanced Interdisciplinary Studies, Henan University, Kaifeng, China
- *Correspondence: Xiangqian Guo,
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Chu CY, Wang R, Liu XL. Roles of Wnt/β-catenin signaling pathway related microRNAs in esophageal cancer. World J Clin Cases 2022; 10:2678-2686. [PMID: 35434118 PMCID: PMC8968815 DOI: 10.12998/wjcc.v10.i9.2678] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 10/25/2021] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs (miRNAs) are endogenous, noncoding, single-stranded small RNAs that regulate expression of tumor suppressor genes and oncogenes and are involved in almost all tumor-related processes. MiRNA dysregulation plays an important role in the occurrence and development of esophageal cancer through specific signal pathways, including the Wnt/β-catenin signaling pathway, and is closely related to the malignant characteristics of esophageal cancer. The interaction between miRNAs and the Wnt/β-catenin signaling pathway, which is specifically expressed in esophageal cancer tissues, shows potential as a new biomarker and therapeutic target. This article reviews the role of miRNAs related to the Wnt pathway in the carcinogenesis of esophageal carcinoma and its role in Wnt signal transduction. The content of this review can be used as the basis for formulating or improving the treatment strategy of esophageal cancer.
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Affiliation(s)
- Chao-Yang Chu
- Gastrointestinal Surgery, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, Henan Province, China
| | - Rui Wang
- Oncology, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, Henan Province, China
| | - Xian-Li Liu
- Gastrointestinal Surgery, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, Henan Province, China
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A Pleiotropic Role of Long Non-Coding RNAs in the Modulation of Wnt/β-Catenin and PI3K/Akt/mTOR Signaling Pathways in Esophageal Squamous Cell Carcinoma: Implication in Chemotherapeutic Drug Response. Curr Oncol 2022; 29:2326-2349. [PMID: 35448163 PMCID: PMC9031703 DOI: 10.3390/curroncol29040189] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 03/19/2022] [Accepted: 03/20/2022] [Indexed: 02/06/2023] Open
Abstract
Despite the availability of modern techniques for the treatment of esophageal squamous cell carcinoma (ESCC), tumor recurrence and metastasis are significant challenges in clinical management. Thus, ESCC possesses a poor prognosis and low five-year overall survival rate. Notably, the origin and recurrence of the cancer phenotype are under the control of complex cancer-related signaling pathways. In this review, we provide comprehensive knowledge about long non-coding RNAs (lncRNAs) related to Wnt/β-catenin and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in ESCC and its implications in hindering the efficacy of chemotherapeutic drugs. We observed that a pool of lncRNAs, such as HERES, TUG1, and UCA1, associated with ESCC, directly or indirectly targets various molecules of the Wnt/β-catenin pathway and facilitates the manifestation of multiple cancer phenotypes, including proliferation, metastasis, relapse, and resistance to anticancer treatment. Additionally, several lncRNAs, such as HCP5 and PTCSC1, modulate PI3K/Akt/mTOR pathways during the ESCC pathogenesis. Furthermore, a few lncRNAs, such as AFAP1-AS1 and LINC01014, block the efficiency of chemotherapeutic drugs, including cisplatin, 5-fluorouracil, paclitaxel, and gefitinib, used for ESCC treatment. Therefore, this review may help in designing a better therapeutic strategy for ESCC patients.
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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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Xu J, Pan HW, Wang XQ, Chen KP. Status of diagnosis and treatment of esophageal cancer and non-coding RNA correlation research: a narrative review. Transl Cancer Res 2021; 10:4532-4552. [PMID: 35116309 PMCID: PMC8798506 DOI: 10.21037/tcr-21-687] [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: 04/21/2021] [Accepted: 08/20/2021] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To describe and discuss the progression of the non-coding RNA as biomarkers in early esophageal cancer. BACKGROUND Esophageal cancer without obvious symptoms during early stages is one of the most common cancers, the current clinical treatments offer possibilities of a cure, but the survival rates and the prognoses remain poor, it is a serious threat to human life and health. Most patients are usually diagnosed during terminal stages due to low sensitivity of esophageal cancer's early detection techniques. With the development of molecular biology, an increasing number of non-coding RNAs are found to be associated with the occurrence, development, and prognosis of esophageal cancer. Some of these have begun to be used in clinics and laboratories for diagnosis, treatment, and prognosis, with the goal of reducing mortality. METHODS The information for this paper was collected from a variety of sources, including a search of the keynote's references, a search for texts in college libraries, and discussions with experts in the field of esophageal cancer clinical treatment. CONCLUSIONS Non-coding RNA does play a regulatory role in the development of esophageal cancer, which can predict the occurrence or prognosis of tumors, and become a new class of tumor markers and therapeutic targets in clinical applications. In this review, we survey the recent developments in the incidence, diagnosis, and treatment of esophageal cancer, especially with new research progresses on non-coding RNA biomarkers in detail, and discuss its potential clinical applications.
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Affiliation(s)
- Jia Xu
- School of Life Sciences, Jiangsu University, Zhenjiang, China
| | - Hui-Wen Pan
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
| | - Xue-Qi Wang
- School of Life Sciences, Jiangsu University, Zhenjiang, China
| | - Ke-Ping Chen
- School of Life Sciences, Jiangsu University, Zhenjiang, China
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Xu J, Liu X, Liu X, Zhi Y. Long noncoding RNA KCNMB2-AS1 promotes the development of esophageal cancer by modulating the miR-3194-3p/PYGL axis. Bioengineered 2021; 12:6687-6702. [PMID: 34516362 PMCID: PMC8806829 DOI: 10.1080/21655979.2021.1973775] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Esophageal cancer (ESCA), as a common cancer worldwide, is a main cause of cancer-related mortality. Comprehensive studies on molecular mechanism of ESCA have been carried out. Though numerous long noncoding RNAs (lncRNAs) was reported to participate in the occurrence and development of ESCA, the potential role of lncRNA potassium calcium-activated channel subfamily M regulatory beta subunit 2 (KCNMB2) antisense RNA 1 (KCNMB2-AS1) in ESCA remains to be discovered. This study intends to investigate the detailed function and molecular mechanism of KCNMB2-AS1 in ESCA. Gene expression was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was examined by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell invasion and migration were measured by wound healing assay and Transwell assay. Luciferase reporter assay was adopted to validate the interaction between KCNMB2-AS1 and miR-3194-3p. Western blotting was performed to assess protein levels. We discovered that KCNMB2-AS1 was significantly upregulated in ESCA. KCNMB2-AS1 downregulation suppressed the growth, invasion, migration and stemness of ESCA cells. KCNMB2-AS1 bound with miR-3194-3p, and glycogen phosphorylase L (PYGL) was a direct target of miR-3194-3p. KCNMB2-AS1 upregulated PYGL expression by directly binding with miR-3194-3p. Additionally, PYGL overexpression abolished the inhibitory influence of KCNMB2-AS1 depletion on ESCA cell behaviors. Collectively, lncRNA KCNMB2-AS1 promotes ESCA development through targeting the miR-3194-3p/ PYGL axis, which might provide theoretical basis to explore novel biomarkers for ESCA treatment.
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Affiliation(s)
- Jiwen Xu
- Department of Gastroenterology, Linyi Traditional Chinese Medical Hospital, Linyi, Shandong, China
| | - Xiaoyan Liu
- Department of Gastroenterology, Linyi Traditional Chinese Medical Hospital, Linyi, Shandong, China
| | - Xueting Liu
- Department of Gastroenterology, Linyi Traditional Chinese Medical Hospital, Linyi, Shandong, China
| | - Yunlai Zhi
- Department of Urology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China
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Xu QR, Tang J, Liao HY, Yu BT, He XY, Zheng YZ, Liu S. Long non-coding RNA MEG3 mediates the miR-149-3p/FOXP3 axis by reducing p53 ubiquitination to exert a suppressive effect on regulatory T cell differentiation and immune escape in esophageal cancer. J Transl Med 2021; 19:264. [PMID: 34140005 PMCID: PMC8212454 DOI: 10.1186/s12967-021-02907-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 05/24/2021] [Indexed: 01/27/2023] Open
Abstract
Background Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been implicated in the progression of esophageal cancer (EC). However, the specific mechanism of the involvement of MEG3 in EC development in relation to the regulation of immune escape remains uncertain. Thus, the aim of the current study was to investigate the effect of MEG3 on EC via microRNA-149-3p (miR-149-3p). Methods Gain- and loss-of-function experiments were initially performed in EC cells in addition to the establishment of a 4-nitroquinoline 1-oxide-induced EC mouse model aimed at evaluating the respective roles of forkhead box P3 (FOXP3), MEG3, miR-149-3p, mouse double minute 2 homolog (MDM2) and p53 in T cell differentiation and immune escape observed in EC. Results EC tissues were found to exhibit upregulated FOXP3 and MDM2 while MEG3, p53 and miR-149-3p were all downregulated. FOXP3 was confirmed to be a target gene of miR-149-3p with our data suggesting it reduced p53 ubiquitination and degradation by means of inhibiting MDM2. P53 was enriched in the promoter of miR-149-3p to upregulate miR-149-3p. The overexpression of MEG3, p53 or miR-149-3p or silencing FOXP3 was associated with a decline in CD25+FOXP3+CD4+ T cells, IL-10+CD4+ T cells and IL-4+CD4+ T cells in spleen tissues, IL-4, and IL-10 levels as well as C-myc, N-myc and Ki-67 expression in EC mice. Conclusion Collectively, MEG3 decreased FOXP3 expression and resulted in repressed regulatory T cell differentiation and immune escape in EC mice by upregulating miR-149-3p via MDM2-mediated p53. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-021-02907-1.
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Affiliation(s)
- Qi-Rong Xu
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People's Republic of China
| | - Jian Tang
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People's Republic of China
| | - Hong-Ying Liao
- Department of Thoracic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen UniversityMedical University, No. 26, Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, Guangdong Province, P. R. China
| | - Ben-Tong Yu
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People's Republic of China
| | - Xiang-Yuan He
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People's Republic of China
| | - Yu-Zhen Zheng
- Department of Thoracic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen UniversityMedical University, No. 26, Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, Guangdong Province, P. R. China.
| | - Sheng Liu
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People's Republic of China.
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Soares-Lima SC, Mehanna H, Camuzi D, de Souza-Santos PT, Simão TDA, Nicolau-Neto P, Almeida Lopes MDS, Cuenin C, Talukdar FR, Batis N, Costa I, Dias F, Degli Esposti D, Boroni M, Herceg Z, Ribeiro Pinto LF. Upper Aerodigestive Tract Squamous Cell Carcinomas Show Distinct Overall DNA Methylation Profiles and Different Molecular Mechanisms behind WNT Signaling Disruption. Cancers (Basel) 2021; 13:3014. [PMID: 34208581 PMCID: PMC8234055 DOI: 10.3390/cancers13123014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 05/27/2021] [Accepted: 06/08/2021] [Indexed: 12/28/2022] Open
Abstract
Upper aerodigestive tract (UADT) tumors present different biological behavior and prognosis, suggesting specific molecular mechanisms underlying their development. However, they are rarely considered as single entities (particularly head and neck subsites) and share the most common genetic alterations. Therefore, there is a need for a better understanding of the global DNA methylation differences among UADT tumors. We performed a genome-wide DNA methylation analysis of esophageal (ESCC), laryngeal (LSCC), oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas, and their non-tumor counterparts. The unsupervised analysis showed that non-tumor tissues present markedly distinct DNA methylation profiles, while tumors are highly heterogeneous. Hypomethylation was more frequent in LSCC and OPSCC, while ESCC and OSCC presented mostly hypermethylation, with the latter showing a CpG island overrepresentation. Differentially methylated regions affected genes in 127 signaling pathways, with only 3.1% of these being common among different tumor subsites, but with different genes affected. The WNT signaling pathway, known to be dysregulated in different epithelial tumors, is a frequent hit for DNA methylation and gene expression alterations in ESCC and OPSCC, but mostly for genetic alterations in LSCC and OSCC. UADT tumor subsites present differences in genome-wide methylation regarding their profile, intensity, genomic regions and signaling pathways affected.
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Affiliation(s)
- Sheila Coelho Soares-Lima
- Molecular Carcinogenesis Program, Brazilian National Cancer Institute, Rua André Cavalcanti, 37–6° Andar, Bairro de Fátima, Rio de Janeiro 20231-050, Brazil; (S.C.S.-L.); (D.C.); (P.N.-N.); (M.d.S.A.L.)
| | - Hisham Mehanna
- Institute of Head and Neck Studies and Education (InHANSE), Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK; (H.M.); (N.B.)
| | - Diego Camuzi
- Molecular Carcinogenesis Program, Brazilian National Cancer Institute, Rua André Cavalcanti, 37–6° Andar, Bairro de Fátima, Rio de Janeiro 20231-050, Brazil; (S.C.S.-L.); (D.C.); (P.N.-N.); (M.d.S.A.L.)
| | | | - Tatiana de Almeida Simão
- Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro 87 fundos, Vila Isabel, Rio de Janeiro 20551-013, Brazil;
| | - Pedro Nicolau-Neto
- Molecular Carcinogenesis Program, Brazilian National Cancer Institute, Rua André Cavalcanti, 37–6° Andar, Bairro de Fátima, Rio de Janeiro 20231-050, Brazil; (S.C.S.-L.); (D.C.); (P.N.-N.); (M.d.S.A.L.)
| | - Monique de Souza Almeida Lopes
- Molecular Carcinogenesis Program, Brazilian National Cancer Institute, Rua André Cavalcanti, 37–6° Andar, Bairro de Fátima, Rio de Janeiro 20231-050, Brazil; (S.C.S.-L.); (D.C.); (P.N.-N.); (M.d.S.A.L.)
| | - Cyrille Cuenin
- Epigenetics Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, CEDEX 08, 69372 Lyon, France; (C.C.); (F.R.T.); (D.D.E.); (Z.H.)
| | - Fazlur Rahman Talukdar
- Epigenetics Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, CEDEX 08, 69372 Lyon, France; (C.C.); (F.R.T.); (D.D.E.); (Z.H.)
| | - Nikolaos Batis
- Institute of Head and Neck Studies and Education (InHANSE), Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK; (H.M.); (N.B.)
| | - Izabella Costa
- Seção de Cirurgia de Cabeça e Pescoço, Instituto Nacional de Câncer—INCA, Praça da Cruz Vermelha, Rio de Janeiro 20230-130, Brazil; (I.C.); (F.D.)
| | - Fernando Dias
- Seção de Cirurgia de Cabeça e Pescoço, Instituto Nacional de Câncer—INCA, Praça da Cruz Vermelha, Rio de Janeiro 20230-130, Brazil; (I.C.); (F.D.)
| | - Davide Degli Esposti
- Epigenetics Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, CEDEX 08, 69372 Lyon, France; (C.C.); (F.R.T.); (D.D.E.); (Z.H.)
| | - Mariana Boroni
- Bioinformatics and Computational Biology Lab, Brazilian National Cancer Institute, Rua André Cavalcanti, 37–1° Andar, Bairro de Fátima, Rio de Janeiro 20231-050, Brazil;
| | - Zdenko Herceg
- Epigenetics Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, CEDEX 08, 69372 Lyon, France; (C.C.); (F.R.T.); (D.D.E.); (Z.H.)
| | - Luis Felipe Ribeiro Pinto
- Molecular Carcinogenesis Program, Brazilian National Cancer Institute, Rua André Cavalcanti, 37–6° Andar, Bairro de Fátima, Rio de Janeiro 20231-050, Brazil; (S.C.S.-L.); (D.C.); (P.N.-N.); (M.d.S.A.L.)
- Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro 87 fundos, Vila Isabel, Rio de Janeiro 20551-013, Brazil;
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Raghav PK, Mann Z. Cancer stem cells targets and combined therapies to prevent cancer recurrence. Life Sci 2021; 277:119465. [PMID: 33831426 DOI: 10.1016/j.lfs.2021.119465] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 03/01/2021] [Accepted: 03/26/2021] [Indexed: 12/12/2022]
Abstract
Cancer stem cells (CSCs) control the dynamics of tumorigenesis by self-renewal ability and differentiation potential. These properties contribute towards tumor malignancy, metastasis, cellular heterogeneity, and immune escape, which are regulated by multiple signaling pathways. The CSCs are chemoresistant and cause cancer recurrence, generally recognized as a small side-population that eventually leads to tumor relapse. Despite many treatment options available, none can be considered entirely efficient due to a lack of specificity and dose limitation. This review primarily highlights the processes involved in CSCs development and maintenance. Secondly, the current effective therapies based on stem cells, cell-free therapies that involve exosomes and miRNAs, and photodynamic therapy have been discussed. Also, the inhibitors that specifically target various signaling pathways, which can be used in combination to control CSCs kinetics have been highlighted. Conclusively, this comprehensive review is a detailed study of recently developed novel treatment strategies that will facilitate in coming up with better-targeted approaches against CSCs.
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Affiliation(s)
| | - Zoya Mann
- Independent Researcher, New Delhi, India
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22
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Luan S, Yang Y, Zhou Y, Zeng X, Xiao X, Liu B, Yuan Y. The emerging role of long noncoding RNAs in esophageal carcinoma: from underlying mechanisms to clinical implications. Cell Mol Life Sci 2021; 78:3403-3422. [PMID: 33464385 PMCID: PMC11071794 DOI: 10.1007/s00018-020-03751-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 12/16/2020] [Accepted: 12/28/2020] [Indexed: 02/08/2023]
Abstract
Long noncoding RNAs (lncRNAs), a type of transcriptional product more than 200 nucleotides in length, have emerged as crucial regulators in human cancers. Accumulating data have recently indicated relationships between lncRNAs and esophageal carcinoma (EC). Of note, lncRNAs act as decoys/sponges, scaffolds, guides, and signals to regulate the expression of oncogenes or tumor suppressors at epigenetic, post-transcriptional, and protein levels, through which they exert their unique EC-driving or EC-suppressive functions. Moreover, the features of EC-related lncRNAs have been gradually exploited for developing novel diagnostic and therapeutic strategies in clinical scenarios. LncRNAs have the potential to be used as diagnostic and prognostic indicators individually or in combination with other clinical variables. Beyond these, although the time is not yet ripe, therapeutically targeting EC-related lncRNAs via gene editing, antisense oligonucleotides, RNA interference, and small molecules is likely one of the most promising therapeutic strategies for the next generation of cancer treatment. Herein, we focus on summarizing EC-driving/suppressive lncRNAs, as well as discussing their different features regarding expression profiles, modes of action, and oncological effects. Moreover, we further discuss current challenges and future developing possibilities of capitalizing on lncRNAs for EC early diagnosis and treatment.
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Affiliation(s)
- Siyuan Luan
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Yushang Yang
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Yuxin Zhou
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Xiaoxi Zeng
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xin Xiao
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Bo Liu
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
| | - Yong Yuan
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
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23
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Comprehensive Analysis of lncRNAs Related to the Prognosis of Esophageal Cancer Based on ceRNA Network and Cox Regression Model. BIOMED RESEARCH INTERNATIONAL 2021; 2020:3075729. [PMID: 33381546 PMCID: PMC7748909 DOI: 10.1155/2020/3075729] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 11/15/2020] [Accepted: 11/21/2020] [Indexed: 01/10/2023]
Abstract
Background Esophageal cancer is one of the most deadly malignant tumors. Among the common malignant tumors in the world, esophageal cancer is ranked seventh, which has a high mortality rate. Long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of various tumors. lncRNAs can competitively bind microRNAs (miRNAs) with mRNA, which can regulate the expression level of the encoded gene at the posttranscriptional level. This regulatory mechanism is called the competitive endogenous RNA (ceRNA) hypothesis, and ceRNA has important research value in tumor-related research. However, the regulation of lncRNAs is less studied in the study of esophageal cancer. Methods The Cancer Genome Atlas (TCGA) database was used to download transcriptome profiling data of esophageal cancer. Gene expression quantification data contains 160 cancer samples and 11 normal samples. These data were used to identify differentially expressed lncRNAs and mRNAs. miRNA expression data includes 185 cancer samples and 13 normal samples. The differentially expressed RNAs were identified using the edgeR package in R software. Then, the miRcode database was used to predict miRNAs that bind to lncRNAs. MiRTarBase, miRDB, and TargetScan databases were used to predict the target genes of miRNAs. Cytoscape software was used to draw ceRNA network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using DAVID 6.8. Finally, multifactor cox regression was used to screen lncRNAs related to prognosis. Results We have screened 1331 DElncRNAs, 3193 DEmRNAs, and 162 DEmiRNAs. Among them, the ceRNA network contains 111 lncRNAs, 11 miRNAs, and 63 DEmRNAs. Finally, we established a prediction model containing three lncRNAs through multifactor Cox regression analysis. Conclusions Our research screened out three independent prognostic lncRNAs from the ceRNA network and constructed a risk assessment model. This is helpful to understand the regulatory role of lncRNAs in esophageal cancer.
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24
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Jiang M, Wang Q, Yu G, Wan J, Liu S, Zhang Z, Le A. Clinical significance of long noncoding RNA maternally expressed gene 3 in acute promyelocytic leukemia. Int J Lab Hematol 2020; 43:693-698. [PMID: 33372415 DOI: 10.1111/ijlh.13438] [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: 06/01/2020] [Revised: 11/20/2020] [Accepted: 11/28/2020] [Indexed: 11/28/2022]
Abstract
INTRODUCTION Long noncoding RNA maternally expressed gene 3 (MEG3) expression was significantly decreased in acute myeloid leukemia (AML). However, its expression and clinical significance in acute promyelocytic leukemia (APL) remain unclear. Thus, the present study aimed to investigate the expression of MEG3 in APL and explore its clinical value. METHODS A total of 287 AML patients derived from The Cancer Genome Atlas (TCGA) and Vizome database were enrolled. A development and validation cohort, including APL, AML with AML1/ETO, and other types of AML patients and disease controls, from the First Affiliated Hospital of Nanchang University, were also enrolled in this study. The correlation between MEG3 expression and the clinicopathological features in APL was investigated. The diagnostic values of MEG3 expression in APL were analyzed by receiver operating characteristic (ROC) curves. RESULT In the development set, MEG3 expression was significantly increased in APL than AML with AML1/ETO, other types of AML, and disease controls, which was consistent with the results from the database analysis. MEG3 expression in APL was associated with age (P = .0053) but did not correlate with other clinicopathological features (P > .05). ROC curve analysis in the development set and diagnostic test analysis in the validation set suggested that MEG3 expression has a significant value in the diagnosis of APL. Furthermore, the expression of MEG3 decreased during the follow-up of patients with negative PML/RARα fusion gene. CONCLUSION MEG3 serves as a novel marker for the diagnosis of APL, evaluates the curative effect, and provides a novel direction for further research.
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Affiliation(s)
- Mei Jiang
- Department of Clinical Laboratory, First Affiliated Hospital of Nanchang University
| | | | | | - Jinghua Wan
- Department of Clinical Laboratory, First Affiliated Hospital of Nanchang University
| | - Shuyuan Liu
- Department of Clinical Laboratory, First Affiliated Hospital of Nanchang University
| | - Zhanglin Zhang
- Department of Transfusion, First Affiliated Hospital of Nanchang University
| | - Aiping Le
- Department of Transfusion, First Affiliated Hospital of Nanchang University
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25
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Zhao J, Liu D, Yang H, Yu S, He H. Long noncoding RNAs in head and neck squamous cell carcinoma: biological functions and mechanisms. Mol Biol Rep 2020; 47:8075-8090. [PMID: 32914266 DOI: 10.1007/s11033-020-05777-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 08/28/2020] [Indexed: 12/22/2022]
Abstract
Head and neck squamous cell carcinoma (HNSCC) is the primary malignant tumor of the oral cavity, larynx, nasopharynx, esophagus and tongue. Although several novel therapeutic methods for HNSCC have been developed, the final therapeutic effect on the patient is still not satisfactory. Thus, it is imperative that scientists identify novel distinguishable markers with specific molecular characteristics that can be used in therapeutic and prognostic evaluation. Previous reports have shown that long noncoding RNAs (lncRNAs) are important regulators of gene expression in many cancers, including head and neck squamous cell carcinomas. Translational studies of lncRNAs in HNSCC are urgently required before their application as a treatment can be realized. We aimed to address the most relevant findings on lncRNAs as biomarkers or treatment targets in head and neck squamous cell carcinoma and to summarize their discovered pathways and mechanisms of action to reveal the possible future applications of these novel biomarkers in clinical translational research.
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Affiliation(s)
- Jiayu Zhao
- Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China
| | - Daming Liu
- Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China
| | - Hao Yang
- Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China
| | - Shan Yu
- Department of Pathology, Second Affiliated Hospital of Harbin Medical University, No. 246 XueFu Avenue, Harbin, 150086, Heilongjiang, China.
| | - Hongjiang He
- Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China.
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26
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Luo Q, Wang S, Han H, Xie F, Chen J. High expression of the long noncoding RNA SH3PXD2A-AS1 is associated with poor prognosis in patients with esophageal squamous cell carcinoma. J Int Med Res 2020. [PMCID: PMC7488910 DOI: 10.1177/0300060520949059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Objective Our objective was to explore the prognostic role of long noncoding RNA (lncRNA) SH3PXD2A-AS1 in esophageal squamous cell carcinoma (ESCC). Methods An SH3PXD2A-AS1 expression dataset was retrieved and analyzed from The Cancer Genome Atlas database, and SH3PXD2A-AS1 expression was determined in our cohort of 134 ESCC patients by using quantitative PCR. The clinical significance of SH3PXD2A-AS1 expression was investigated by the Chi square test and its prognostic value was determined by Kaplan–Meier survival curve analysis and Cox proportional hazards analysis. RNA interference and in vitro functional experiments, including cell viability, migration, and invasion, were used to investigate effects of SH3PXD2A-AS1 on cell malignant phenotype. Results SH3PXD2A-AS1 expression was increased in ESCC tissues compared with adjacent normal tissues. A high level of SH3PXD2A-AS1 expression was associated with poor tumor differentiation and advanced T, N, and TNM stages, indicating its oncogenic role in ESCC. Moreover, its high expression predicted poor overall survival in patients with ESCC. Inhibition of SH3PXD2A-AS1 expression significantly suppressed cell viability, migration, and invasion of ESCC cells. Conclusion High SH3PXD2A-AS1 expression is a poor prognostic factor for patients with ESCC. SH3PXD2A-AS1 might function as an oncogene that can promote malignant biological characteristics of ESCC cells.
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Affiliation(s)
- Qiuli Luo
- College of Life Science and Bioengineering, Beijing University of Technology, Beijing, China
| | - Shanshan Wang
- Department of Clinical Laboratory, Peking University Cancer Hospital & Institute, Beijing, China
| | - Haibo Han
- Department of Clinical Laboratory, Peking University Cancer Hospital & Institute, Beijing, China
| | - Fei Xie
- College of Life Science and Bioengineering, Beijing University of Technology, Beijing, China
| | - Jinfeng Chen
- Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
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27
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Zhou SN. Role of non-coding RNAs in esophageal carcinoma. Shijie Huaren Xiaohua Zazhi 2020; 28:453-459. [DOI: 10.11569/wcjd.v28.i12.453] [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
In recent years, the research on the role of non-coding RNAs (ncRNAs) in tumors has received more and more attention. Although research on the role of ncRNAs in the early diagnosis, disease monitoring, treatment guidance, and prognosis prediction of esophageal carcinoma has been gradually carried out, there are still many problems that need to be addressed. In the current paper, I review the progress in the research of ncRNAs in esophageal carcinoma, with an aim to help provide new strategies for the prevention and treatment of esophageal carcinoma.
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Affiliation(s)
- Su-Na Zhou
- Department of Radiation Oncology, The Affiliated Taizhou Hospital, Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
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28
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Talebi A, Masoodi M, Mirzaei A, Mehrad-Majd H, Azizpour M, Akbari A. Biological and clinical relevance of metastasis-associated long noncoding RNAs in esophageal squamous cell carcinoma: A systematic review. J Cell Physiol 2020; 235:848-868. [PMID: 31310341 DOI: 10.1002/jcp.29083] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Accepted: 06/21/2019] [Indexed: 12/12/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) is a foremost cancer-related death worldwide owing to rapid metastasis and poor prognosis. Metastasis, as the most important reason for death, is biologically a multifaceted process involving a range of cell signaling pathways. Long noncoding RNAs (lncRNAs), as transcriptional regulators, can regulate numerous genomic processes and cellular processes such as cell proliferation, migration, and invasion. LncRNAs have also been shown to involve in/regulate the cancer metastasis-related signaling pathways. Hence, they have increasingly been brought to international attention in molecular oncology research. A number of researchers have attempted to reveal the biological and clinical relevance of lncRNAs in ESCC tumourigenesis and metastasis. The aberrant expression of these molecules in ESCC has regularly been reported to involve in various cellular processes and clinical features, including diagnosis, prognosis, and therapeutic responses. Here, we especially consider the pathways in which lncRNAs act as metastasis-mediated effectors, mainly by interacting with epithelial-mesenchymal transition-associated factors. We review the biological roles of lncRNAs through involving in ESCC metastasis as well as the clinical significance of the metastasis-related lncRNAs in cancer diagnosis and prognosis.
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Affiliation(s)
- Atefeh Talebi
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mohsen Masoodi
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Alireza Mirzaei
- Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Hassan Mehrad-Majd
- Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mazaher Azizpour
- Department of Orthopedic Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - Abolfazl Akbari
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
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29
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Ghafouri-Fard S, Mohammad-Rahimi H, Jazaeri M, Taheri M. Expression and function of long non-coding RNAs in head and neck squamous cell carcinoma. Exp Mol Pathol 2020; 112:104353. [DOI: 10.1016/j.yexmp.2019.104353] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 11/25/2019] [Accepted: 12/04/2019] [Indexed: 12/31/2022]
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Emerging Role of Non-Coding RNAs in Esophageal Squamous Cell Carcinoma. Int J Mol Sci 2019; 21:ijms21010258. [PMID: 31905958 PMCID: PMC6982002 DOI: 10.3390/ijms21010258] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 12/04/2019] [Accepted: 12/14/2019] [Indexed: 12/14/2022] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a highly prevalent tumor and is associated with ethnicity, genetics, and dietary intake. Non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) have been reported as functional regulatory molecules involved in the development of many human cancers, including ESCC. Recently, several ncRNAs have been detected as oncogenes or tumor suppressors in ESCC progression. These ncRNAs influence the expression of specific genes or their associated signaling pathways. Moreover, interactions of ncRNAs are evident in ESCC, as miRNAs regulate the expression of lncRNAs, and further, lncRNAs and circRNAs function as miRNA sponges to compete with the endogenous RNAs. Here, we discuss and summarize the findings of recent investigations into the role of ncRNAs (miRNAs, lncRNAs, and circRNAs) in the development and progression of ESCC and how their interactions regulate ESCC development.
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31
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Du FY, Zhou QF, Sun WJ, Chen GL. Targeting cancer stem cells in drug discovery: Current state and future perspectives. World J Stem Cells 2019; 11:398-420. [PMID: 31396368 PMCID: PMC6682504 DOI: 10.4252/wjsc.v11.i7.398] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 06/18/2019] [Accepted: 06/27/2019] [Indexed: 02/06/2023] Open
Abstract
In recent decades, cancer stem cells (CSCs) have been increasingly identified in many malignancies. CSC-related signaling pathways and their functions provide new strategies for treating cancer. The aberrant activation of related signaling pathways (e.g., Wnt, Notch, and Hedgehog pathways) has been linked to multiple types of malignant tumors, which makes these pathways attractive targets for cancer therapy. CSCs display many characteristic features, such as self-renewal, differentiation, high tumorigenicity, and drug resistance. Therefore, there is an urgent need to develop new therapeutic strategies to target these pathways to control stem cell replication, survival, and differentiation. Notable crosstalk occurs among different signaling pathways and potentially leads to compensatory escape. Therefore, multitarget inhibitors will be one of the main methods to overcome the drug resistance of CSCs. Many small molecule inhibitors of components of signaling pathways in CSCs have entered clinical trials, and some inhibitors, such as vismodegib, sonidegib, and glasdegib, have been approved. Tumor cells are susceptible to sonidegib and vismodegib resistance due to mutations in the Smo protein. The signal transducers and activators of transcription 3 (STAT3) inhibitor BBI608 is being evaluated in a phase III trial for a variety of cancers. Structural derivatives of BBI608 are the main focus of STAT3 inhibitor development, which is another strategy for CSC therapy. In addition to the potential pharmacological inhibitors targeting CSC-related signaling pathways, other methods of targeting CSCs are available, such as nano-drug delivery systems, mitochondrion targeting, autophagy, hyperthermia, immunotherapy, and CSC microenvironment targeting. In addition, we summarize the latest advances in the clinical development of agents targeting CSC-related signaling pathways and other methods of targeting CSCs.
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Affiliation(s)
- Fang-Yu Du
- Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning Province, China
| | - Qi-Fan Zhou
- Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning Province, China
| | - Wen-Jiao Sun
- Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning Province, China
| | - Guo-Liang Chen
- Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning Province, China
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