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1
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Sil S, Bertilla J, Rupachandra S. A comprehensive review on RNA interference-mediated targeting of interleukins and its potential therapeutic implications in colon cancer. 3 Biotech 2023; 13:18. [PMID: 36568500 PMCID: PMC9768089 DOI: 10.1007/s13205-022-03421-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: 04/18/2022] [Accepted: 12/05/2022] [Indexed: 12/24/2022] Open
Abstract
Colon cancer is the world's fourth leading cause of death. It is cancer of the latter part of the large intestine, i.e. the colon. Chronic inflammation over a long period also leads to the development of cancer. Cancer in the colon region is arduous to diagnose and is detected at a later stage when it metastasizes to other parts of the body like the liver, lungs, peritoneum, etc. Colon cancer is a great example of solid tumours associated with chronic inflammation. Although conventional therapies are effective, they lose their effectiveness beyond a certain point. Relapse of the disease occurs frequently. RNA interference (RNAi) is emerging as a great tool to specifically attack the cancer cells of a target site like the colon. RNAi deals with epigenetic changes made in the defective cells which ultimately leads to their death without harming the healthy cells. In this review, two types of epigenetic modulators have been considered, namely siRNA and miRNA, and their effect on interleukins. Interleukins, a class of cytokines, are major inflammatory responses of the body that are released by immune cells like leukocytes and macrophages. Some of these interleukins are pro-inflammatory, thereby promoting inflammation which eventually causes cancer. RNAi can prevent colon cancer by inhibiting pro-inflammatory interleukins.
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Affiliation(s)
- Sagari Sil
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, Tamil Nadu 603 203 India
| | - Janet Bertilla
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, Tamil Nadu 603 203 India
| | - S. Rupachandra
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, Tamil Nadu 603 203 India
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2
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Elrebehy MA, Al-Saeed S, Gamal S, El-Sayed A, Ahmed AA, Waheed O, Ismail A, El-Mahdy HA, Sallam AAM, Doghish AS. miRNAs as cornerstones in colorectal cancer pathogenesis and resistance to therapy: A spotlight on signaling pathways interplay - A review. Int J Biol Macromol 2022; 214:583-600. [PMID: 35768045 DOI: 10.1016/j.ijbiomac.2022.06.134] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/18/2022] [Accepted: 06/19/2022] [Indexed: 02/07/2023]
Abstract
Colorectal cancer (CRC) is the world's third most prevalent cancer and the main cause of cancer-related mortality. A lot of work has been put into improving CRC patients' clinical care, including the development of more effective methods and wide biomarkers variety for prognostic, and diagnostic purposes. MicroRNAs (miRNAs) regulate a variety of cellular processes and play a significant role in the CRC progression and spread via controlling their target gene expression by translation inhibition or mRNA degradation. Consequently, dysregulation and disruption in their function, miRNAs are linked to CRC malignant pathogenesis by controlling several cellular processes involved in the CRC. These cellular processes include increased proliferative and invasive capacity, cell cycle aberration, evasion of apoptosis, enhanced EMT, promotion of angiogenesis and metastasis, and decreased sensitivity to major treatments. The miRNAs control cellular processes in CRC via regulation of pathways such as Wnt/β-catenin signaling, PTEN/AKT/mTOR axis, KRAS, TGFb signaling, VEGFR, EGFR, and P53. Hence, the goal of this review was to review miRNA biogenesis and present an updated summary of oncogenic and tumor suppressor (TS) miRNAs and their potential implication in CRC pathogenesis and responses to chemotherapy and radiotherapy. We also summarise the biological importance and clinical applications of miRNAs in the CRC.
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Affiliation(s)
- Mahmoud A Elrebehy
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Sarah Al-Saeed
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Sara Gamal
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Asmaa El-Sayed
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Alshaimaa A Ahmed
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Omnia Waheed
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Ahmed Ismail
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Hesham A El-Mahdy
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Al-Aliaa M Sallam
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry Department, Faculty of Pharmacy, Ain-Shams University, Abassia, Cairo 11566, Egypt
| | - 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.
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3
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Braoudaki M, Ahmad MS, Mustafov D, Seriah S, Siddiqui MN, Siddiqui SS. Chemokines and chemokine receptors in colorectal cancer; multifarious roles and clinical impact. Semin Cancer Biol 2022; 86:436-449. [PMID: 35700938 DOI: 10.1016/j.semcancer.2022.06.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/07/2022] [Accepted: 06/08/2022] [Indexed: 11/19/2022]
Abstract
Colorectal cancer (CRC) is considered the second cause of cancer death worldwide. The early diagnosis plays a key role in patient prognosis and subsequently overall survival. Similar to several types of cancer, colorectal cancer is also characterised by drug resistance and heterogeneity that contribute to its complexity -especially at advanced stages. However, despite the extensive research related to the identification of biomarkers associated to early diagnosis, accurate prognosis and the management of CRC patients, little progress has been made thus far. Therefore, the mortality rates, especially at advanced stages, remain high. A large family of chemoattractant cytokines called chemokines are known for their significant role in inflammation and immunity. Chemokines released by the different tumorous cells play a key role in increasing the complexity of the tumour's microenvironment. The current review investigates the role of chemokines and chemokine receptors in colorectal cancer and their potential as clinical molecular signatures that could be effectively used as a personalised therapeutic approach. We discussed how chemokine and chemokine receptors regulate the microenvironment and lead to heterogeneity in CRC. An important aspect of chemokines is their role in drug resistance which has been extensively discussed. This review also provides an overview of the current advances in the search for chemokines and chemokine receptors in CRC.
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Affiliation(s)
- Maria Braoudaki
- Dept of Clinical, Pharmaceutical and Biological Sciences, School of Life and Medical Sciences, University of Hertfordshire, UK
| | - Mohammed Saqif Ahmad
- Dept of Clinical, Pharmaceutical and Biological Sciences, School of Life and Medical Sciences, University of Hertfordshire, UK
| | - Denis Mustafov
- Dept of Clinical, Pharmaceutical and Biological Sciences, School of Life and Medical Sciences, University of Hertfordshire, UK
| | - Sara Seriah
- Dept of Clinical, Pharmaceutical and Biological Sciences, School of Life and Medical Sciences, University of Hertfordshire, UK
| | - Mohammad Naseem Siddiqui
- Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Shoib Sarwar Siddiqui
- Dept of Clinical, Pharmaceutical and Biological Sciences, School of Life and Medical Sciences, University of Hertfordshire, UK.
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Wu Z, Ju Q. Non-Coding RNAs Implicated in the Tumor Microenvironment of Colorectal Cancer: Roles, Mechanisms and Clinical Study. Front Oncol 2022; 12:888276. [PMID: 35574420 PMCID: PMC9096125 DOI: 10.3389/fonc.2022.888276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 04/04/2022] [Indexed: 11/21/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignant tumors. The morbidity and mortality rates have been increasing all over the world. It is critical to elucidate the mechanism of CRC occurrence and development. However, tumor microenvironment (TME) includes immune cells, fibroblasts, endothelial cells, cytokines, chemokines and other components that affect the progression of CRC and patients' prognosis. Non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) without protein-coding ability have been shown to engage in tumor microenvironment-mediated angiogenesis and metastasis. Therefore, clarifying the mechanism of ncRNAs regulating the microenvironment is very important to develop the therapeutic target of CRC and improve the survival time of patients. This review focuses on the role and mechanism of ncRNAs in the CRC microenvironment and puts forward possible clinical treatment strategies.
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Affiliation(s)
| | - Qiang Ju
- Department of Blood Transfusion, The Affiliated Hospital of Qingdao University, Qingdao, China
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Plundrich D, Chikhladze S, Fichtner-Feigl S, Feuerstein R, Briquez PS. Molecular Mechanisms of Tumor Immunomodulation in the Microenvironment of Colorectal Cancer. Int J Mol Sci 2022; 23:2782. [PMID: 35269922 PMCID: PMC8910988 DOI: 10.3390/ijms23052782] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 02/24/2022] [Accepted: 02/25/2022] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer remains one of the most important health challenges in our society. The development of cancer immunotherapies has fostered the need to better understand the anti-tumor immune mechanisms at play in the tumor microenvironment and the strategies by which the tumor escapes them. In this review, we provide an overview of the molecular interactions that regulate tumor inflammation. We particularly discuss immunomodulatory cell-cell interactions, cell-soluble factor interactions, cell-extracellular matrix interactions and cell-microbiome interactions. While doing so, we highlight relevant examples of tumor immunomodulation in colorectal cancer.
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Affiliation(s)
- Dorothea Plundrich
- Department of General and Visceral Surgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
| | - Sophia Chikhladze
- Department of General and Visceral Surgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
- Department of Biomedical Sciences, Cedars-Sinai Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 900048, USA
- Department of Medicine, Cedars-Sinai Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 900048, USA
| | - Stefan Fichtner-Feigl
- Department of General and Visceral Surgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
| | - Reinhild Feuerstein
- Department of General and Visceral Surgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
| | - Priscilla S Briquez
- Department of General and Visceral Surgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
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Zhu Y, Li J, Liu H, Song Z, Yang Q, Lu C, Chen W. Circular RNA, hsa_circRNA_102049, promotes colorectal cancer cell migration and invasion via binding and suppressing miRNA-455-3p. Exp Ther Med 2022; 23:244. [PMID: 35222721 PMCID: PMC8815054 DOI: 10.3892/etm.2022.11169] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Accepted: 04/28/2021] [Indexed: 11/25/2022] Open
Abstract
Colorectal cancer (CRC) is the second most prevalent malignant gastrointestinal tumor type worldwide, displaying poor prognosis. Accumulating studies have reported the significance of circular RNAs (circRNAs) and microRNAs (miRNAs) in CRC carcinogenesis and development. At present, the functions and mechanisms of action underlying the circular RNA, hsa_circRNA_102049, in CRC are not completely understood. The present study aimed to establish the involvement of hsa_circRNA_102049 in CRC, as well as the associated mechanisms. The expression levels of hsa_circRNA_102049 and miRNA-455-3p were measured in CRC cell lines and tissues via reverse transcription-quantitative PCR. CRC progression was evaluated by performing Cell Counting Kit-8, flow cytometry, wound healing and Transwell invasion assays. The results demonstrated that hsa_circRNA_102049 was highly expressed in both CRC tissues and cell lines, which was associated with enhanced CRC cell proliferation, migration and invasion. Furthermore, miR-455-3p expression was downregulated in CRC cells and served as a target of has_circRNA_102049, which was validated by performing the dual luciferase reporter assay. hsa_circRNA_102049 knockdown significantly increased miR-455-3p expression, which was significantly reversed by co-transfection with the miR-455-3p inhibitor. Notably, miRNA-455-3p overexpression alleviated hsa_circRNA_102049-mediated induction of CRC cell proliferation, migration and invasion. The present study clearly demonstrated that miRNA-455-3p was a target of hsa_circRNA_102049. Moreover, the results indicated that the circular RNA, hsa_circRNA_102049, may function as a tumor promoter in CRC via directly sponging miRNA-455-3p.
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Affiliation(s)
- Yuandong Zhu
- Department of Colorectal and Anal Surgery, Yiwu Central Hospital, Yiwu, Zhejiang 322000, P.R. China
| | - Jianjion Li
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Haiyuan Liu
- Department of Colorectal and Anal Surgery, Yiwu Central Hospital, Yiwu, Zhejiang 322000, P.R. China
| | - Zhengming Song
- Department of Colorectal and Anal Surgery, Yiwu Central Hospital, Yiwu, Zhejiang 322000, P.R. China
| | - Qinghua Yang
- Department of Colorectal and Anal Surgery, Yiwu Central Hospital, Yiwu, Zhejiang 322000, P.R. China
| | - Chengdong Lu
- Department of Colorectal and Anal Surgery, Yiwu Central Hospital, Yiwu, Zhejiang 322000, P.R. China
| | - Wenbin Chen
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
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He D, Ruan ZB, Song GX, Chen GC, Wang F, Wang MX, Yuan MK, Zhu L. miR-15a-5p regulates myocardial fibrosis in atrial fibrillation by targeting Smad7. PeerJ 2022; 9:e12686. [PMID: 35036160 PMCID: PMC8697763 DOI: 10.7717/peerj.12686] [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: 08/23/2021] [Accepted: 12/03/2021] [Indexed: 01/25/2023] Open
Abstract
Background At present, there is no effective treatment for myocardial fibrosis in atrial fibrillation (AF). It is reported that miR-15a-5p is abnormally expressed in AF patients but its specific role remains unclear. This study aims to investigate the effect of miR-15a-5p in myocardial fibrosis. Methods Left atrial appendage (LAA) tissues were collected from AF and non-AF patients. In lipopolysaccharide (LPS) stimulated H9C2 cells, miR-15a-5p mimic, inhibitor, pcDNA3.1-Smad7 and small interfering RNA-Smad7 (siRNA-Smad7) were respectively transfected to up-regulate or down-regulate the intracellular expression levels of miR-15a-5p and Smad7. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) were used to determine the expression levels of miR-15a-5p, Smad7, transforming growth factor β1 (TGF-β1) and collagen I. Cell counting kit-8 (CCK-8) and ethylene deoxyuridine (EdU) were used to determine cell viability and proliferation capacity, respectively. Dual-luciferase was used to detect whether miR-15a-5p interacted with Smad7, hydroxyproline (HYP) and Hematoxylin-Eosin (HE) staining were used to detect tissue fibrosis. Results The expression levels of miR-15a-5p, TGF-β1 and collagen I were up-regulated, while Smad7 was down-regulated in AF tissues and LPS-stimulated cells. MiR-15a-5p mimic can inhibit the expression of Smad7, and the dual-luciferase experiment confirmed their interaction. MiR-15a-5p inhibitor or pcDNA3.1-Smad7 can inhibit LPS-induced fibrosis and cell proliferation, while siRNA-Smad7 can reverse the changes caused by miR-15a-5p inhibitor. Conclusion We combined clinical studies with LPS-stimulated H9C2 cell model to validate the role of miR-15a-5p in the regulation of Smad7 and fibrosis. Taken together, the miR-15a-5p/Smad7 pathway might be a potential target for AF therapy.
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Affiliation(s)
- Dan He
- Department of Cardiology, Jiangsu Taizhou People's Hospital, Taizhou, China.,Dalian Medical University Graduate School of Medicine, dalian, China
| | - Zhong-Bao Ruan
- Department of Cardiology, Jiangsu Taizhou People's Hospital, Taizhou, China.,Dalian Medical University Graduate School of Medicine, dalian, China
| | - Gui-Xian Song
- Department of Cardiology, Jiangsu Taizhou People's Hospital, Taizhou, China
| | - Ge-Cai Chen
- Department of Cardiology, Jiangsu Taizhou People's Hospital, Taizhou, China
| | - Fei Wang
- Department of Cardiology, Jiangsu Taizhou People's Hospital, Taizhou, China
| | - Mei-Xiang Wang
- Department of Cardiology, Jiangsu Taizhou People's Hospital, Taizhou, China
| | - Mao-Kun Yuan
- Department of Cardiothoracic Surgery, Jiangsu Taizhou People's Hospital, Taizhou, China
| | - Li Zhu
- Department of Cardiology, Jiangsu Taizhou People's Hospital, Taizhou, China
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Tan L, Qu W, Wu D, Liu M, Wang Q, Ai Q, Hu H, Chen M, Chen W, Zhou H. GRHL3 Promotes Tumor Growth and Metastasis via the MEK Pathway in Colorectal Cancer. Anal Cell Pathol (Amst) 2021; 2021:6004821. [PMID: 34888136 PMCID: PMC8651427 DOI: 10.1155/2021/6004821] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 10/26/2021] [Indexed: 11/28/2022] Open
Abstract
GRHL3 is a factor associated with a tumor, of which the molecular mechanism remains a further investigation. We explored the underlying mechanism of tumor-promoting effect of GRHL3 in colorectal cancer (CRC), which is involved in the MEK1/2 pathway. The expression of GRHL3 was measured in CRC and adjacent normal tissue using qPCR and immunohistochemical staining. Lentivirus-mediated knockdown expression of GRHL3 was performed in the CRC cell line HT29. Cell proliferation and metastasis were assayed in vitro, and tumorigenicity was investigated in vivo. We found higher GRHL3 expression in colorectal cancer, which was negatively correlated with patients' prognosis. Results from studies in vitro and in vivo indicated that downregulation of GRHL3 expression inhibited tumor growth and metastasis and inhibited the activation of the MEK1/2 pathway. The effect of GRHL3 downexpression was the same as that of MEK1/2 antagonists on suppression of tumor growth and metastasis. Our results suggested that GRHL3 may act as an oncogene to promote tumor growth and metastasis via the MEK pathway in colorectal cancer.
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Affiliation(s)
- Lin Tan
- Department of Gastroenterology, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, China 412007
| | - Weiming Qu
- Department of Gastroenterology, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, China 412007
| | - Dajun Wu
- Department of Gastroenterology, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, China 412007
| | - Minji Liu
- Department of Gastroenterology, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, China 412007
| | - Qian Wang
- Department of Gastroenterology, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, China 412007
| | - Qiongjia Ai
- Department of Gastroenterology, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, China 412007
| | - Hongsai Hu
- Department of Gastroenterology, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, China 412007
| | - Min Chen
- Department of Gastroenterology, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, China 412007
| | - Weishun Chen
- Department of Gastroenterology, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, China 412007
| | - Hongbing Zhou
- Department of Gastroenterology, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, China 412007
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Investigation of miRNA dysregulation and association with immune cell profile during malignant transformation of colorectal cells. Eur J Surg Oncol 2021; 48:245-252. [PMID: 34620510 DOI: 10.1016/j.ejso.2021.09.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 09/01/2021] [Accepted: 09/21/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most prevalent and life-threatening cancer among the world. Accumulated somatic mutations during malignant transformation process endow cancer cells with increased growth, invasiveness and immunogenicity. These highly immunogenic cancer cells develop multiple strategies to evade immune attack. Through post-transcriptional regulation, microRNAs (miRNAs) not only participate in cancer development and progression but also manipulate anti-cancer immune response. This study aims to identify miRNAs associated with the colorectal cell malignant transformation process and their association with immune cell population using synchronous adjacent normal, polyp and CRC specimens. METHODS We conducted a Low Density Array to compare the miRNA expression profile of synchronous colorectal adenoma, adenocarcinoma and adjacent normal colon mucosa collected from 8 patients, in order to identify candidate miRNAs involved in CRC progression. These findings were further validated in 14 additional patients and GEO dataset GSE41655. The relative abundance of dendritic cells, natural killer cells, neutrophil and macrophage was determined and correlated with dysregulated miRNA levels. RESULTS MicroRNA microarray identified 39 miRNAs aberrantly expressed during the colorectal cell transformation process. Seven novel miRNAs were shortlisted, and dysregulation of miR-149-3p, miR-192-3p, miR-335-5p and miR-425 were further validated by the qPCR validation experiment and data retrieved from the GEO dataset. Furthermore, these miRNAs demonstrated certain associations with level of dendritic cells, natural killer cells, neutrophil and macrophage within the polyp or CRC specimens. CONCLUSION This study revealed miRNA dysregulated during stepwise malignant transformation of colorectal mucosal cells and their association with immune cell population.
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Liu Z, Lu T, Wang Y, Jiao D, Li Z, Wang L, Liu L, Guo C, Zhao Y, Han X. Establishment and experimental validation of an immune miRNA signature for assessing prognosis and immune landscape of patients with colorectal cancer. J Cell Mol Med 2021; 25:6874-6886. [PMID: 34101338 PMCID: PMC8278100 DOI: 10.1111/jcmm.16696] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 05/11/2021] [Accepted: 05/14/2021] [Indexed: 02/06/2023] Open
Abstract
As essential regulators of gene expression, miRNAs are engaged in the initiation and progression of colorectal cancer (CRC), including antitumour immune response. In this study, we proposed an integrated algorithm, ImmuMiRNA, for identifying miRNA modulators of immune‐associated pathways. Based on these immune‐associated miRNAs, we applied the LASSO algorithm to develop a reliable and individualized signature for evaluating overall survival (OS) and inflammatory landscape of CRC patients. An external public data set and qRT‐PCR data from 40 samples were further utilized to validate this signature. As a result, an immune‐associated miRNA prognostic signature (IAMIPS) consisting of three miRNAs (miR‐194‐3P, miR‐216a‐5p and miR‐3677‐3p) was established and validated. Patients in the high‐risk group possessed worse OS. After stratification for clinical factors, the signature remained a powerful independent predictor for OS. IAMIPS displayed much better accuracy than the traditional clinical stage in assessing the prognosis of CRC. Further analysis revealed that patients in the high‐risk group were characterized by inflammatory response, abundance immune cell infiltration, and higher immune checkpoint profiles and tumour mutation burden (TMB). In conclusion, the IAMIPS is highly predictive of OS in patients with CRC, which may serve as a powerful prognostic tool to further optimize immunotherapies for cancer.
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Affiliation(s)
- Zaoqu Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Taoyuan Lu
- Department of Cerebrovascular Disease, Zhengzhou University People's Hospital, Zhengzhou, China
| | - Yanli Wang
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Dechao Jiao
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhaonan Li
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Libo Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Long Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Chunguang Guo
- Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yanan Zhao
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xinwei Han
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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11
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Garo LP, Ajay AK, Fujiwara M, Gabriely G, Raheja R, Kuhn C, Kenyon B, Skillin N, Kadowaki-Saga R, Saxena S, Murugaiyan G. MicroRNA-146a limits tumorigenic inflammation in colorectal cancer. Nat Commun 2021; 12:2419. [PMID: 33893298 PMCID: PMC8065171 DOI: 10.1038/s41467-021-22641-y] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 03/24/2021] [Indexed: 02/07/2023] Open
Abstract
Chronic inflammation can drive tumor development. Here, we have identified microRNA-146a (miR-146a) as a major negative regulator of colonic inflammation and associated tumorigenesis by modulating IL-17 responses. MiR-146a-deficient mice are susceptible to both colitis-associated and sporadic colorectal cancer (CRC), presenting with enhanced tumorigenic IL-17 signaling. Within myeloid cells, miR-146a targets RIPK2, a NOD2 signaling intermediate, to limit myeloid cell-derived IL-17-inducing cytokines and restrict colonic IL-17. Accordingly, myeloid-specific miR-146a deletion promotes CRC. Moreover, within intestinal epithelial cells (IECs), miR-146a targets TRAF6, an IL-17R signaling intermediate, to restrict IEC responsiveness to IL-17. MiR-146a within IECs further suppresses CRC by targeting PTGES2, a PGE2 synthesis enzyme. IEC-specific miR-146a deletion therefore promotes CRC. Importantly, preclinical administration of miR-146a mimic, or small molecule inhibition of the miR-146a targets, TRAF6 and RIPK2, ameliorates colonic inflammation and CRC. MiR-146a overexpression or miR-146a target inhibition represent therapeutic approaches that limit pathways converging on tumorigenic IL-17 signaling in CRC.
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Affiliation(s)
- Lucien P Garo
- Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Boston University School of Medicine, Boston, MA, USA
| | - Amrendra K Ajay
- Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Mai Fujiwara
- Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Galina Gabriely
- Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Radhika Raheja
- Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Chantal Kuhn
- Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Brendan Kenyon
- Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Nathaniel Skillin
- Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Ryoko Kadowaki-Saga
- Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Shrishti Saxena
- Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Gopal Murugaiyan
- Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
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12
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Peruhova M, Peshevska-Sekulovska M, Krastev B, Panayotova G, Georgieva V, Konakchieva R, Nikolaev G, Velikova TV. What could microRNA expression tell us more about colorectal serrated pathway carcinogenesis? World J Gastroenterol 2020; 26:6556-6571. [PMID: 33268946 PMCID: PMC7673963 DOI: 10.3748/wjg.v26.i42.6556] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2020] [Revised: 09/24/2020] [Accepted: 10/20/2020] [Indexed: 02/06/2023] Open
Abstract
In the last two decades, the vision of a unique carcinogenesis model for colorectal carcinoma (CRC) has completely changed. In addition to the adenoma to carcinoma transition, colorectal carcinogenesis can also occur via the serrated pathway. Small non-coding RNA, known as microRNAs (miRNAs), were also shown to be involved in progression towards malignancy. Furthermore, increased expression of certain miRNAs in premalignant sessile serrated lesions (SSLs) was found, emphasizing their role in the serrated pathway progression towards colon cancer. Since miRNAs function as post-transcriptional gene regulators, they have enormous potential to be used as useful biomarkers for CRC and screening in patients with SSLs particularly. In this review, we have summarized the most relevant information about the specific role of miRNAs and their relevant signaling pathways among different serrated lesions and polyps as well as in serrated adenocarcinoma. Additional focus is put on the correlation between gut immunity and miRNA expression in the serrated pathway, which remains unstudied.
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Affiliation(s)
- Milena Peruhova
- Department of Gastroenterology, University Hospital Lozenetz, Sofia 1407, Bulgaria
- Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria
| | | | - Boris Krastev
- Department of Clinical Oncology, MHAT Hospital for Women Health Nadezhda, Sofia 1330, Bulgaria
| | - Gabriela Panayotova
- Department of Gastroenterology, University Hospital Lozenetz, Sofia 1407, Bulgaria
- Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria
| | - Viktoriya Georgieva
- Department of Gastroenterology, University Hospital Lozenetz, Sofia 1407, Bulgaria
| | | | - Georgi Nikolaev
- Faculty of Biology, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria
| | - Tsvetelina Veselinova Velikova
- Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria
- Department of Clinical Immunology, University Hospital Lozenetz, Sofia 1407, Bulgaria
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13
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Muthusami S, Ramachandran IK, Babu KN, Krishnamoorthy S, Guruswamy A, Queimado L, Chaudhuri G, Ramachandran I. Role of Inflammation in the Development of Colorectal Cancer. Endocr Metab Immune Disord Drug Targets 2020; 21:77-90. [PMID: 32901590 DOI: 10.2174/1871530320666200909092908] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Revised: 07/23/2020] [Accepted: 07/29/2020] [Indexed: 11/22/2022]
Abstract
Chronic inflammation can lead to the development of many diseases, including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohnmp's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation, together with genetic and epigenetic changes, have been shown to lead to the development and progression of CRC. Various cell types present in the colon, such as enterocytes, Paneth cells, goblet cells, and macrophages, express receptors for inflammatory cytokines and respond to tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key pro-inflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of pro-inflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy) to alleviate the symptoms or treat inflammation-associated CRC by using monoclonal antibodies or aptamers to block pro-inflammatory molecules, inhibitors of tyrosine kinases in the inflammatory signaling cascade, competitive inhibitors of pro-inflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/pro-inflammatory cytokine gene expression.
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Affiliation(s)
- Sridhar Muthusami
- Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore 641 021, Tamil Nadu, India
| | | | - Kokelavani Nampalli Babu
- Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore 641 021, Tamil Nadu, India
| | - Sneha Krishnamoorthy
- Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore 641 021, Tamil Nadu, India
| | - Akash Guruswamy
- University of Missouri- Kansas City, College of Medicine, Kansas City, MO 64110, United States
| | - Lurdes Queimado
- Departments of Otorhinolaryngology - Head and Neck Surgery, Cell Biology, Pediatrics, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States
| | - Gautam Chaudhuri
- Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, United States
| | - Ilangovan Ramachandran
- Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, United States
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14
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Sammarco G, Gallo G, Vescio G, Picciariello A, De Paola G, Trompetto M, Currò G, Ammendola M. Mast Cells, microRNAs and Others: The Role of Translational Research on Colorectal Cancer in the Forthcoming Era of Precision Medicine. J Clin Med 2020; 9:jcm9092852. [PMID: 32899322 PMCID: PMC7564551 DOI: 10.3390/jcm9092852] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 08/31/2020] [Accepted: 09/01/2020] [Indexed: 12/13/2022] Open
Abstract
Colorectal cancer (CRC) is a heterogeneous disease, molecularly and anatomically, that develops in a multi-step process requiring the accumulation of several genetic or epigenetic mutations that lead to the gradual transformation of normal mucosa into cancer. In fact, tumorigenesis is extremely complex, with many immunologic and non-immunologic factors present in the tumor microenvironment that can influence tumorigenesis. In the last few years, a role for mast cells (MCs), microRNAs (miRNAs), Kirsten rat sarcoma (KRAS) and v-raf murine sarcoma viral oncogene homologue B (BRAF) in cancer development and progression has been suggested, and numerous efforts have been made to thoroughly assess their correlation with CRC to improve patient survival and quality of life. The identification of easily measurable, non-invasive and cost-effective biomarkers, the so-called "ideal biomarkers", for CRC screening and treatment remains a high priority. The aim of this review is to discuss the emerging role of mast cells (MCs), microRNAs (miRNAs), KRAS and BRAF as diagnostic and prognostic biomarkers for CRC, evaluating their influence as potential therapy targets in the forthcoming era of precision medicine.
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Affiliation(s)
- Giuseppe Sammarco
- Department of Health Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (G.S.); (G.C.); (M.A.)
| | - Gaetano Gallo
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (G.V.); (G.D.P.)
- Correspondence: ; Tel.: +39-32-8438-5222
| | - Giuseppina Vescio
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (G.V.); (G.D.P.)
| | - Arcangelo Picciariello
- Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, Piazza G Cesare, 11, 70124 Bari, Italy;
| | - Gilda De Paola
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (G.V.); (G.D.P.)
| | - Mario Trompetto
- Department of Colorectal Surgery, S. Rita Clinic, 13100 Vercelli, Italy;
| | - Giuseppe Currò
- Department of Health Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (G.S.); (G.C.); (M.A.)
| | - Michele Ammendola
- Department of Health Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (G.S.); (G.C.); (M.A.)
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15
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Epigenetic Mechanisms of Resistance to Immune Checkpoint Inhibitors. Biomolecules 2020; 10:biom10071061. [PMID: 32708698 PMCID: PMC7407667 DOI: 10.3390/biom10071061] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 07/13/2020] [Accepted: 07/13/2020] [Indexed: 02/06/2023] Open
Abstract
Immune checkpoint inhibitors (ICIs) have demonstrated to be highly efficient in treating solid tumors; however, many patients have limited benefits in terms of response and survival. This rapidly led to the investigation of combination therapies to enhance response rates. Moreover, predictive biomarkers were assessed to better select patients. Although PD-L1 expression remains the only validated marker in clinics, molecular profiling has brought valuable information, showing that the tumor mutation load and microsatellite instability (MSI) status were associated to higher response rates in nearly all cancer types. Moreover, in lung cancer, EGFR and MET mutations, oncogene fusions or STK11 inactivating mutations were associated with low response rates. Cancer progression towards invasive phenotypes that impede immune surveillance relies on complex regulatory networks and cell interactions within the tumor microenvironment. Epigenetic modifications, such as the alteration of histone patterns, chromatin structure, DNA methylation status at specific promoters and changes in microRNA levels, may alter the cell phenotype and reshape the tumor microenvironment, allowing cells to grow and escape from immune surveillance. The objective of this review is to make an update on the identified epigenetic changes that target immune surveillance and, ultimately, ICI responses, such as histone marks, DNA methylation and miR signatures. Translational studies or clinical trials, when available, and potential epigenetic biomarkers will be discussed as perspectives in the context of combination treatment strategies to enhance ICI responses in patients with solid tumors.
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16
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Cong J, Gong J, Yang C, Xia Z, Zhang H. miR-22 Suppresses Tumor Invasion and Metastasis in Colorectal Cancer by Targeting NLRP3. Cancer Manag Res 2020; 12:5419-5429. [PMID: 32753959 PMCID: PMC7351629 DOI: 10.2147/cmar.s255125] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 06/09/2020] [Indexed: 12/19/2022] Open
Abstract
Purpose This study aimed to investigate the effects of microRNA (miR)-22 on biological behaviors of colon cancer cells and to explore the relationship between miR-22 and NLRP3. Materials and Methods First, human colon cancer HCT116 cells were transfected with a miR-22 mimic, miR-22 inhibitor, control mimic, and control inhibitor, respectively. CCK8, colony formation, and transwell assays were performed to observe cell proliferation, migration, and invasion. Western blotting was used to analyze the expression of recombinant NLRP3 (NLR family, pyrin domain-containing protein 3) and epithelial–mesenchymal transformation (EMT)-related proteins. The target relationship between miR-22 and NLRP3 was verified by double luciferase report. Second, an NLRP3 inhibitor and NLRP3 mimic were transfected into HCT116 cells, and the biological behaviors and EMT-related proteins were again observed. Finally, a nude mouse xenograft model was constructed to verify the above results. Results In vitro, compared with the control group, administration of the miR-22 mimic significantly decreased proliferation, migration, and invasion of HCT116 cells, whereas the miR-22 inhibitor markedly increased their proliferation and invasion (p<0.05). Levels of NLRP3, interleukin-1β (IL-1β), matrix metalloproteinase-9 (MMP-9), MMP-2, N-cadherin, and vimentin were significantly reduced after miR-22 mimic transfection (p<0.05). Furthermore, silencing of NLRP3, a downstream gene of miR-22 in HCT116 cells, suppressed proliferation, migration, and invasion of HCT116 cells. However, overexpression of NLRP3 weakened the effects of the miR-22 mimic. In vivo, overexpression of miR-22 slowed the growth rate of tumors and reduced Ki-67 expression in tumor tissues compared with the model group (p<0.05). In tumor tissues, overexpression of miR-22 also decreased expression of NLRP3, IL-1β, MMP-9, MMP-2, N-cadherin, and vimentin compared with the model group (p<0.05). Overexpression of NLRP3 weakened the role of miR-22 overexpression in vivo. Conclusion miR-22 suppresses cell proliferation, migration, and invasion in colorectal cancer by targeting NLRP3.
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Affiliation(s)
- Jinchun Cong
- Department of Colorectal Tumor Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China
| | - Jian Gong
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China
| | - Chuanjia Yang
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110016, People's Republic of China
| | - Zhixiu Xia
- Department of Colorectal Tumor Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China
| | - Hong Zhang
- Department of Colorectal Tumor Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China
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17
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Ji T, Feng W, Zhang X, Zang K, Zhu X, Shang F. HDAC inhibitors promote pancreatic stellate cell apoptosis and relieve pancreatic fibrosis by upregulating miR-15/16 in chronic pancreatitis. Hum Cell 2020; 33:1006-1016. [PMID: 32524326 PMCID: PMC7505886 DOI: 10.1007/s13577-020-00387-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Accepted: 06/04/2020] [Indexed: 12/21/2022]
Abstract
In chronic pancreatitis, PSCs are activated by proinflammatory cytokines to induce pancreatic fibrogenesis. HDAC inhibition protected against the pancreatic fibrosis and the apoptosis of PSCs through induced apoptosis and depressed inflammation. In our study, we found that miR-15 and miR-16 decreased significantly in chronic pancreatitis and HDAC inhibition could recover the levels of these two miRNAs. HDAC regulated the transcription of miR-15 and miR-16, which then modulate the apoptosis and fibrosis of PSCs. And we proved that Bcl-2 and Smad5 were the target genes of miR-15 and miR-16, which illustrated how HDAC inhibition alleviated the apoptosis and fibrogenesis of PSCs in chronic pancreatitis. These results suggested that HDAC inhibition protects against CP by promoting apoptosis and TGF-β/Smads signaling pathways, and indicated that HDAC inhibition is a potential therapy to alleviate CP patients in clinic, and these need to be explored further.
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Affiliation(s)
- Ting Ji
- Intensive Care Unit, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Beijing West Road, Huaiyin District, Huai'an, 223300, Jiangsu, China
| | - Weiguang Feng
- Intensive Care Unit, Huai'an No 4 People's Hospital, 128 Yan'an East Road, Qingjiangpu District, Huai'an, 223002, Jiangsu, China
| | - Xiangcheng Zhang
- Intensive Care Unit, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Beijing West Road, Huaiyin District, Huai'an, 223300, Jiangsu, China
| | - Kui Zang
- Intensive Care Unit, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Beijing West Road, Huaiyin District, Huai'an, 223300, Jiangsu, China
| | - Xingxing Zhu
- Intensive Care Unit, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Beijing West Road, Huaiyin District, Huai'an, 223300, Jiangsu, China
| | - Futai Shang
- Intensive Care Unit, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Beijing West Road, Huaiyin District, Huai'an, 223300, Jiangsu, China.
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18
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Yang Y, Meng WJ, Wang ZQ. MicroRNAs in Colon and Rectal Cancer - Novel Biomarkers from Diagnosis to Therapy. Endocr Metab Immune Disord Drug Targets 2020; 20:1211-1226. [PMID: 32370729 DOI: 10.2174/1871530320666200506075219] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 01/31/2020] [Accepted: 02/01/2020] [Indexed: 02/05/2023]
Abstract
Colorectal cancer (CRC) is one of the most common cancers and a significant cause of tumor- related deaths worldwide. Traditional biomarkers, such as CEA and CA199, are not sensitive enough to provide useful information for early diagnosis and treatment and are rather used to track the clinical progression of the disease. There is growing evidence that microRNAs (miRNA) are potentially superior to traditional biomarkers as promising non-invasive biomarkers for the timely diagnosis and prediction of prognosis or treatment response in the management of CRC. In this review, the latest studies on the dysregulation of miRNAs expression in CRC and the potential for miRNAs to serve as biomarkers were collected. Given the limitations of miRNA, as discussed in this paper, its clinical applications as a diagnostic biomarker should be limited to use in combination with other biomarkers. Further research is necessary to elucidate the clinical applications of miRNA in therapy for CRC.
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Affiliation(s)
- Ying Yang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Wen-Jian Meng
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Zi-Qiang Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
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19
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Filipovic A, Miller G, Bolen J. Progress Toward Identifying Exact Proxies for Predicting Response to Immunotherapies. Front Cell Dev Biol 2020; 8:155. [PMID: 32258034 PMCID: PMC7092703 DOI: 10.3389/fcell.2020.00155] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 02/26/2020] [Indexed: 12/14/2022] Open
Abstract
Clinical value and utility of checkpoint inhibitors, a drug class targeting adaptive immune suppression pathways (PD-1, PDL-1, and CTLA-4), is growing rapidly and maintains status of a landmark achievement in oncology. Their efficacy has transformed life expectancy in multiple deadly cancer types (melanoma, lung cancer, renal/urothelial carcinoma, certain colorectal cancers, lymphomas, etc.). Despite significant clinical development efforts, therapeutic indication of approved checkpoint inhibitors are not as wide as the oncology community and patients would like them to be, potentially bringing into question their universal efficacy across tumor histologies. With the main goal of expanding immunotherapy applications, identifying of biomarkers to accurately predict therapeutic response and treatment related side-effects are a paramount need in the field. Specificities surrounding checkpoint inhibitors in clinic, such as unexpected tumor response patterns (pseudo- and hyper-progression), late responders, as well as specific immune mediated toxicities, complicate the management of patients. They stem from the complexities and dynamics of the tumor/host immune interactions, as well as baseline tumor biology. Search for clinically effective biomarkers therefore calls for a holistic approach, rather than implementation of a single analyte. The goal is to achieve dynamic and comprehensive acquisition, analyses and interpretation of immunological and biologic information about the tumor and the immune system, and to compute these parameters into an actionable, maximally predictive value at the individual patient level. Limitation delaying swift incorporation of validated immuno-oncology biomarkers span from standardized biospecimens acquisition and processing, selection of proficient biomarker discovery and validation methods, to establishing multidisciplinary consortiums and data sharing platforms. Multi-disciplinary efforts have already yielded some approved (PDL-1 and MSI-status) and other advanced tests (TMB, neoantigen pattern, and TIL infiltration rate). Importantly, clinical trial taskforces now recognize the imperative of the biomarker-driven trial design and execution, to enable translating biomarker discoveries into the clinical setting. This will ensure we utilize the “conspiracy” between the peripheral and intra-tumoral dynamic markers in shaping responses to checkpoint blockade, for the ultimate patient benefit.
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Affiliation(s)
| | - George Miller
- New York University School of Medicine, New York, NY, United States
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20
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Shindo Y, Hazama S, Tsunedomi R, Suzuki N, Nagano H. Novel Biomarkers for Personalized Cancer Immunotherapy. Cancers (Basel) 2019; 11:E1223. [PMID: 31443339 PMCID: PMC6770350 DOI: 10.3390/cancers11091223] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Revised: 08/17/2019] [Accepted: 08/19/2019] [Indexed: 02/07/2023] Open
Abstract
Cancer immunotherapy has emerged as a novel and effective treatment strategy for several types of cancer. Immune checkpoint inhibitors (ICIs) have recently demonstrated impressive clinical benefit in some advanced cancers. Nonetheless, in the majority of patients, the successful use of ICIs is limited by a low response rate, high treatment cost, and treatment-related toxicity. Therefore, it is necessary to identify predictive and prognostic biomarkers to select the patients who are most likely to benefit from, and respond well to, these therapies. In this review, we summarize the evidence for candidate biomarkers of response to cancer immunotherapy.
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Affiliation(s)
- Yoshitaro Shindo
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan
| | - Shoichi Hazama
- Department of Translational Research and Developmental Therapeutics against Cancer, Yamaguchi University Faculty of Medicine, Ube 755-8505, Japan
| | - Ryouichi Tsunedomi
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan
| | - Nobuaki Suzuki
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
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21
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Li T, Zhou W, Li Y, Gan Y, Peng Y, Xiao Q, Ouyang C, Wu A, Zhang S, Liu J, Fan L, Han D, Wei Y, Shu G, Yin G. MiR-4524b-5p/WTX/β-catenin axis functions as a regulator of metastasis in cervical cancer. PLoS One 2019; 14:e0214822. [PMID: 30939162 PMCID: PMC6445517 DOI: 10.1371/journal.pone.0214822] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 03/20/2019] [Indexed: 12/12/2022] Open
Abstract
Cervical cancer is the second most deadly gynecological tumor worldwide. MicroRNAs (miRNAs) play very important roles in tumor oncogenesis and progression. The mechanism of post-transcription regulation of WTX gene is still unknown. A series of differential miRNAs were discovered by microarray analysis comparing three pairs of primary cervical cancer specimens and their relapsed tumors from three patients. Quantitative reverse transcriptase PCR (qRT-PCR), Western Blot (WB) and Immunohistochemistry (IHC) was used to detect the expression of miR-4524b-5p and WTX in cervical cell lines and tissues. The biological function of miR-4524b-5p and WTX was investigated through knockdown and overexpression with inhibitor/siRNA and mimic/plasmid in vitro and in vivo. In this study, we found that miR-4524b-5p is highly expressed in relapsed cervical cancer specimens. Combined in vitro and in vivo experiments, showed that miR-4524b-5p could regulate the migration and invasion ability of cervical cancer. Furthermore, we also found that miR-4524b-5p could regulate the migration and invasion of cervical cancer by targeting WTX and that WTX could regulate the expression of β-catenin. Taken together, our data identified a miR-4524b-5p/WTX/β-catenin regulatory axis for cervical cancer, and miR-4524b-5p may be a potential target for cervical cancer therapy.
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Affiliation(s)
- Tong Li
- Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Wenjuan Zhou
- Xiangya School of Nursing, Central South University, Changsha, China
| | - Yimin Li
- Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Yaqi Gan
- Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Yulong Peng
- Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Qing Xiao
- Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Chunli Ouyang
- Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Anqi Wu
- Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Sai Zhang
- Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Jiaqi Liu
- Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Lili Fan
- Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Duo Han
- Department of General Surgery, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Yu Wei
- School of Life Science, Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China
| | - Guang Shu
- Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Gang Yin
- Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China
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22
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Proença MA, Biselli JM, Succi M, Severino FE, Berardinelli GN, Caetano A, Reis RM, Hughes DJ, Silva AE. Relationship between Fusobacterium nucleatum, inflammatory mediators and microRNAs in colorectal carcinogenesis. World J Gastroenterol 2018; 24:5351-5365. [PMID: 30598580 PMCID: PMC6305535 DOI: 10.3748/wjg.v24.i47.5351] [Citation(s) in RCA: 84] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 11/29/2018] [Accepted: 12/13/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To examine the effect of Fusobacterium nucleatum (F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs (miRNAs).
METHODS Levels of F. nucleatum DNA, cytokine gene mRNA (TLR2, TLR4, NFKB1, TNF, IL1B, IL6 and IL8), and potentially interacting miRNAs (miR-21-3p, miR-22-3p, miR-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction (qPCR) TaqMan® assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma (CRA) and 43 colorectal cancer (CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability (MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.
RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA (51.8%) and more markedly in CRC (72.1%). We observed significantly greater expression of TLR4, IL1B, IL8, and miR-135b in CRA lesions and TLR2, IL1B, IL6, IL8, miR-34a and miR-135b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.
CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible miRNA-mediated activation of TLR2/TLR4.
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Affiliation(s)
- Marcela Alcântara Proença
- Department of Biology, UNESP, Univ. Estadual Paulista, Campus of São José do Rio Preto, São José do Rio Preto, São Paulo 15054-000, Brazil
| | - Joice Matos Biselli
- Department of Biology, UNESP, Univ. Estadual Paulista, Campus of São José do Rio Preto, São José do Rio Preto, São Paulo 15054-000, Brazil
| | - Maysa Succi
- Department of Biology, UNESP, Univ. Estadual Paulista, Campus of São José do Rio Preto, São José do Rio Preto, São Paulo 15054-000, Brazil
| | - Fábio Eduardo Severino
- Department of Surgery and Orthopedics, Faculty of Medicine, UNESP, Univ. Estadual Paulista, Campus of Botucatu, Botucatu, São Paulo 18618-687, Brazil
| | | | - Alaor Caetano
- Endoscopy Center of Rio Preto, São José do Rio Preto, São Paulo 15015-700, Brazil
| | - Rui Manuel Reis
- Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo 14784-400, Brazil
- Life and Health Sciences Research Institute, University of Minho, Campus Gualtar, Braga 4710-057, Portugal
- ICVS/3B’s-PT Government Associate Laboratory, Campus Gualtar, Braga 4710-057, Portugal
| | - David J Hughes
- Cancer Biology and Therapeutics Group, UCD Conway Institute, University College Dublin, Dublin D04 V1W8, Ireland
| | - Ana Elizabete Silva
- Department of Biology, UNESP, Univ. Estadual Paulista, Campus of São José do Rio Preto, São José do Rio Preto, São Paulo 15054-000, Brazil
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23
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Darvin P, Toor SM, Sasidharan Nair V, Elkord E. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med 2018; 50:1-11. [PMID: 30546008 PMCID: PMC6292890 DOI: 10.1038/s12276-018-0191-1] [Citation(s) in RCA: 1429] [Impact Index Per Article: 204.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Revised: 08/22/2018] [Accepted: 09/19/2018] [Indexed: 02/07/2023] Open
Abstract
Cancer growth and progression are associated with immune suppression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. Monoclonal antibodies that target immune checkpoints provided an immense breakthrough in cancer therapeutics. Among the immune checkpoint inhibitors, PD-1/PD-L1 and CTLA-4 inhibitors showed promising therapeutic outcomes, and some have been approved for certain cancer treatments, while others are under clinical trials. Recent reports have shown that patients with various malignancies benefit from immune checkpoint inhibitor treatment. However, mainstream initiation of immune checkpoint therapy to treat cancers is obstructed by the low response rate and immune-related adverse events in some cancer patients. This has given rise to the need for developing sets of biomarkers that predict the response to immune checkpoint blockade and immune-related adverse events. In this review, we discuss different predictive biomarkers for anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors, including immune cells, PD-L1 overexpression, neoantigens, and genetic and epigenetic signatures. Potential approaches for further developing highly reliable predictive biomarkers should facilitate patient selection for and decision-making related to immune checkpoint inhibitor-based therapies.
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Affiliation(s)
- Pramod Darvin
- Cancer Research Center, Qatar Biomedical Research Institute, College of Science and Engineering, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar
| | - Salman M Toor
- Cancer Research Center, Qatar Biomedical Research Institute, College of Science and Engineering, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar
| | - Varun Sasidharan Nair
- Cancer Research Center, Qatar Biomedical Research Institute, College of Science and Engineering, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar
| | - Eyad Elkord
- Cancer Research Center, Qatar Biomedical Research Institute, College of Science and Engineering, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.
- Institute of Cancer Sciences, University of Manchester, Manchester, UK.
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24
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Shou T, Yang H, Lv J, Liu D, Sun X. MicroRNA‑3666 suppresses the growth and migration of glioblastoma cells by targeting KDM2A. Mol Med Rep 2018; 19:1049-1055. [PMID: 30483744 PMCID: PMC6323202 DOI: 10.3892/mmr.2018.9698] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Accepted: 07/27/2018] [Indexed: 12/20/2022] Open
Abstract
MicroRNAs (miRNAs) are acknowledged as essential regulators in human cancer types, including glioblastoma (GBM). However, the functions of microRNA-3666 (miR-3666) in GBM remain unclear. In the present study, it was identified that the expression of miR-3666 was significantly downregulated in GBM tissues compared with adjacent normal tissues by reverse transcription-quantitative polymerase chain reaction. Additionally, miR-3666 was downregulated in GBM cell lines. Furthermore, it was observed that the miR-3666 expression level in patients with GBM was associated with prognosis. With functional experiments, it was identified that overexpression of miR-3666 significantly inhibited the proliferation, migration and invasion of GBM cells in vitro by Cell Counting kit-8 and Transwell assays. Ectopic expression of miR-3666 significantly arrested GBM cells in the G0 phase by fluorescence activated cell sorting. In terms of the underlying mechanism, it was identified that lysine-specific demethylase 2A (KDM2A) is a direct target of miR-3666 in GBM cells. Overexpression of miR-3666 significantly decreased the expression of KDM2A in GBM cells. Furthermore, it was observed that knockdown of KDM2A significantly suppressed the proliferation, migration and invasion of GBM cells. Collectively, the present results demonstrated that the miR-3666/KDM2A axis serves an important role in the progression of GBM, which provides novel insight into the development of therapeutic strategies for GBM treatment.
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Affiliation(s)
- Taotao Shou
- Department of Neurosurgery, The Affiliated Huai'an No. 1 Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
| | - Huyin Yang
- Department of Neurosurgery, The Affiliated Huai'an No. 1 Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
| | - Jia Lv
- Department of Neurosurgery, The Affiliated Huai'an No. 1 Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
| | - Dai Liu
- Department of Neurosurgery, The Affiliated Huai'an No. 1 Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
| | - Xiaoyang Sun
- Department of Neurosurgery, The Affiliated Huai'an No. 1 Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
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25
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Zhang J, Wang Z, Han X, Jiang L, Ge R, Wang X, Li J. Up-regulation of microRNA-19b is associated with metastasis and predicts poor prognosis in patients with colorectal cancer. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2018; 11:3952-3960. [PMID: 31949783 PMCID: PMC6962803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 06/29/2018] [Indexed: 06/10/2023]
Abstract
Recent evidence has demonstrated that microRNA-19b (miR-19b) is elevated and functions as a prognosis predictor in hepatocellular carcinoma and melanoma. However, its expression and clinical significance in colorectal cancer (CRC) remain unclear. The study aimed to identify the correlation between miR-19b expression and the clinicopathological features and prognosis of patients with CRC. In this study, we found that the levels of miR-19b were significantly up-regulated in CRC tissues and cell lines compared with matched adjacent non-cancerous tissues and human colon mucosal epithelial cell lines, and its expression was also increased in patients with lymph node metastasis compared with those patients with no lymph node metastasis. Meanwhile, the patients with distal metastasis have a higher miR-19b expression than those patients with no distal metastasis. The high expression of miR-19b in patients with CRC was associated with lymph node metastasis and distant metastasis. miR-19b expression was an independent prognostic indicator for overall survival of CRC patients. Moreover, patients with a high miR-19b expression have shorter overall survival times than those patients with a low miR-19b expression. In addition, an in vitro functional assay showed that miR-19b knockdown restrained the migration and invasion of HCT116 and SW480 cells. In summary, the study provides the first convincing statistical and experimental evidence that the up-regulation of miR-19b is associated with metastasis and predicts unfavorable prognosis in patients with CRC, suggesting that miR-19b may serve as a novel and promising prognostic biomarker in CRC.
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Affiliation(s)
- Jingjing Zhang
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical CollegeBengbu, People’s Republic of China
| | - Zian Wang
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical CollegeBengbu, People’s Republic of China
| | - Xiao Han
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical CollegeBengbu, People’s Republic of China
| | - Lei Jiang
- Department of General Surgery, The Second Affiliated Hospital of Bengbu Medical CollegeBengbu, People’s Republic of China
| | - Rongjing Ge
- Department of Pathophysiology, School of Basic Medicine, Bengbu Medical CollegeBengbu, People’s Republic of China
| | - Xiu Wang
- Department of Pharmacy, Bengbu Medical CollegeBengbu 233030, People’s Republic of China
| | - Jiajia Li
- Department of Hematology, The First Affiliated Hospital of Bengbu Medical CollegeBengbu, People’s Republic of China
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26
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Otsuka T, Tahara T, Nakamura M, Jing W, Ota M, Nomura T, Hayashi R, Shimasaki T, Shibata T, Arisawa T. Polymorphism rs7521584 in miR‑429 is associated with the severity of atrophic gastritis in patients with Helicobacter pylori infection. Mol Med Rep 2018; 18:2381-2386. [PMID: 29956763 DOI: 10.3892/mmr.2018.9200] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 03/01/2017] [Indexed: 12/16/2022] Open
Abstract
The aim of the present study was to investigate an association of genetic polymorphism (rs7521584) located in miR‑200a‑200b‑429 cluster, which has tumor suppressor and pro‑inflammatory function, with the development of gastric mucosal atrophy and metaplasia as a pre‑malignant condition. Gastric mucosa samples were obtained from the antrum of 393 patients with no malignancies. The rs7521584 genotype was determined using the polymerase chain reaction‑single‑strand conformation polymorphism analysis method. The degree of gastritis was assessed histologically in all subjects and serum levels of pepsinogen (PG) I/II were quantified in 123 out of 393 patients. Patients with an atrophy score ≥1 and metaplasia score ≥1 were classified into the atrophic gastritis group (AG group). The rs7521584 TT genotype was significantly associated with the development of atrophic gastritis [odds ratio (OR), 2.41; 95% confidence interval (CI), 1.10‑5.25; P=0.027), particularly in patients with H. pylori infection (OR, 3.31; 95% CI, 1.35‑8.12; P=0.0089). In addition, in patients younger than 60 years of age, this genotype was associated with atrophic gastritis (OR, 3.15; 95% CI 1.03‑9.61; P=0.044)]. In patients with H. pylori infection, the metaplasia score was significantly higher in the TT homozygote compared with the GG+GT genotype. In the rs7521584 TT homozygote, serum PG I/II ratio was significantly reduced with increasing age (P=0.0084). No significant trend was identified between the GG+GT genotype and age. The results of the current study indicated that the rs7521584 minor allele homozygote was associated with the development of chronic gastritis under the influence of H. pylori‑induced inflammation, particularly with the severity of metaplastic alterations.
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Affiliation(s)
- Toshimi Otsuka
- Department of Gastroenterology, Kanazawa Medical University, Uchinada‑machi, Ishikawa 920‑0293, Japan
| | - Tomomitsu Tahara
- Department of Gastroenterology, Fujita Health University, Toyoake, Aichi 470‑1192, Japan
| | - Masakatsu Nakamura
- Department of Gastroenterology, Kanazawa Medical University, Uchinada‑machi, Ishikawa 920‑0293, Japan
| | - Wu Jing
- Department of Gastroenterology, Kanazawa Medical University, Uchinada‑machi, Ishikawa 920‑0293, Japan
| | - Masafumi Ota
- Department of Gastroenterology, Kanazawa Medical University, Uchinada‑machi, Ishikawa 920‑0293, Japan
| | - Tomoe Nomura
- Department of Gastroenterology, Kanazawa Medical University, Uchinada‑machi, Ishikawa 920‑0293, Japan
| | - Ranji Hayashi
- Department of Gastroenterology, Kanazawa Medical University, Uchinada‑machi, Ishikawa 920‑0293, Japan
| | - Takeo Shimasaki
- Department of Gastroenterology, Kanazawa Medical University, Uchinada‑machi, Ishikawa 920‑0293, Japan
| | - Tomoyuki Shibata
- Department of Gastroenterology, Fujita Health University, Toyoake, Aichi 470‑1192, Japan
| | - Tomiyasu Arisawa
- Department of Gastroenterology, Kanazawa Medical University, Uchinada‑machi, Ishikawa 920‑0293, Japan
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Yang Y, Alderman C, Sehlaoui A, Xiao Y, Wang W. MicroRNAs as Immunotherapy Targets for Treating Gastroenterological Cancers. Can J Gastroenterol Hepatol 2018; 2018:9740357. [PMID: 30046565 PMCID: PMC6038585 DOI: 10.1155/2018/9740357] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Accepted: 05/02/2018] [Indexed: 01/17/2023] Open
Abstract
Gastroenterological cancers are the most common cancers categorized by systems and are estimated to comprise 18.4% of all cancers in the United States in 2017. Gastroenterological cancers are estimated to contribute 26.2% of cancer-related death in 2017. Gastroenterological cancers are characterized by late diagnosis, metastasis, high recurrence, and being refractory to current therapies. Since the current targeted therapies provide limited benefit to the overall response and survival, there is an urgent need for developing novel therapeutic strategy to improve the outcome of gastroenterological cancers. Immunotherapy has been developed and underwent clinical trials, but displayed limited therapeutic benefit. Since aberrant expressions of miRNAs are found in gastroenterological cancers and miRNAs have been shown to regulate antitumor immunity, the combination therapy combining the traditional antibody-based immunotherapy and novel miRNA-based immunotherapy is promising for achieving clinical success. This review summarizes the current knowledge about the miRNAs and long noncoding RNAs that exhibit immunoregulatory roles in gastroenterological cancers and precancerous diseases of digestive system, as well as the miRNA-based clinical trials for gastroenterological cancers. This review also analyzes the ongoing challenge of identifying appropriate therapy candidates for complex and dynamic tumor microenvironment, ensuring efficient and targeted delivery to specific cancer tissues, and developing strategy for avoiding off-target effect.
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Affiliation(s)
- Yixin Yang
- College of Natural, Applied and Health Sciences, Kean University, 100 Morris Avenue, Union, NJ 07083, USA
| | - Christopher Alderman
- School of Medicine, University of Colorado, 13001 E 17th Pl, Aurora, CO 80045, USA
| | - Ayoub Sehlaoui
- Department of Biological Sciences, Emporia State University, 1 Kellogg Circle, Emporia, KS 66801, USA
| | - Yuan Xiao
- Department of Biological Sciences, Emporia State University, 1 Kellogg Circle, Emporia, KS 66801, USA
| | - Wei Wang
- Department of Thoracic Surgery III, Cancer Hospital of China Medical University, No. 44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning 110042, China
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28
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Sun Y, Wang Y, Yang H, Xu Y, Yu H. miR-455-3p functions as a tumor suppressor in colorectal cancer and inhibits cell proliferation by targeting TPT1. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2018; 11:2522-2529. [PMID: 31938365 PMCID: PMC6958251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Accepted: 03/23/2018] [Indexed: 06/10/2023]
Abstract
Increasing studies have revealed the importance of microRNAs (miRNAs) in tumorigenesis and tumor progression. miR-455-3p is a newly identified tumor suppressive RNA in various human cancers. However, the expression pattern and clinical significance of miR-455-3p in colorectal cancer (CRC) remains unclear. We found that expression of miR-455-3p was significantly reduced in CRC tissues and cell lines. In addition, we show that low miR-455-3p expression is associated with larger tumor size, advanced tumor stage, and poorer overall survival of CRC patients. Furthermore, in vitro experiments revealed that overexpression of miR-455-3p represses cell proliferation. Importantly, we show that the tumor protein translationally controlled 1 (TPT1) is a direct target of miR-455-3p. Moreover, expression of TPT1 was inversely correlated with the expression of miR-455-3p. Loss-of-function of TPT1 had a similar effect on CRC cell proliferation in vitro as gain-of-function of miR-455-3p. Taken together, these data suggest that miR-455-3p functions as tumor suppressive RNA by targeting TPT1 in CRC, and it might be a potential therapeutic target for CRC patients.
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Affiliation(s)
- Yuanyuan Sun
- Department of Medical Oncology, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Beijing Key Lab of Therapeutic Cancer VaccinesBeijing, P. R. China
| | - Yan Wang
- Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy for TianjinTianjin, P. R. China
| | - Hainan Yang
- Department of Medical Oncology, The Ninth Teaching Hospital of Peking University Health Science Center, Beijing Shijitan Hospital, Beijing Key Lab of Therapeutic Cancer VaccinesBeijing, P. R. China
| | - Yan Xu
- Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy for TianjinTianjin, P. R. China
| | - Haipeng Yu
- Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy for TianjinTianjin, P. R. China
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29
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Wang Y, Lu Z, Wang N, Feng J, Zhang J, Luan L, Zhao W, Zeng X. Long noncoding RNA DANCR promotes colorectal cancer proliferation and metastasis via miR-577 sponging. Exp Mol Med 2018; 50:1-17. [PMID: 29717105 PMCID: PMC5938019 DOI: 10.1038/s12276-018-0082-5] [Citation(s) in RCA: 80] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 01/23/2018] [Accepted: 02/14/2018] [Indexed: 12/12/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) play key roles in various malignant tumors, including colorectal cancer (CRC). Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) is overexpressed in CRC patients, but whether it affects CRC proliferation and metastasis via regulation of heat shock protein 27 (HSP27) remains unclear. In the present study, we found that DANCR was highly expressed and correlated with proliferation and metastasis in CRC. In addition, we demonstrated that DANCR and HSP27 were both targets of microRNA-577 (miR-577) and shared the same binding site. Furthermore, we revealed that DANCR promoted HSP27 expression and its mediation of proliferation/metastasis via miR-577 sponging. Finally, using an in vivo study, we confirmed that overexpression of DANCR promoted CRC tumor growth and liver metastasis. The present study demonstrated the function of DANCR in CRC and might provide a new target in the treatment of CRC.
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Affiliation(s)
- Yong Wang
- The 4th Department of Orthopedic Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110024, China
| | - Zhi Lu
- Department of Nuclear Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China
| | - Ningnin Wang
- The 2nd Department of Cardiology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110024, China
| | - Jianzhou Feng
- The 4th Department of Orthopedic Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110024, China
| | - Junjie Zhang
- Department of Pathology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110024, China
| | - Lan Luan
- Department of Pathology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110024, China
| | - Wei Zhao
- The 4th Department of Orthopedic Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110024, China
| | - Xiandong Zeng
- Department of Surgical Oncology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110024, China.
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30
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Jiang D, Wang H, Li Z, Li Z, Chen X, Cai H. MiR-142 inhibits the development of cervical cancer by targeting HMGB1. Oncotarget 2018; 8:4001-4007. [PMID: 27829233 PMCID: PMC5354809 DOI: 10.18632/oncotarget.13136] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 10/28/2016] [Indexed: 01/01/2023] Open
Abstract
It has been reported that miRNAs is deregulated in diverse human cancers, involving human cervical cancer. However, the clinical significances and potential mechanisms of miR-142 in the development and progression of cervical cancer were not elucidated completely till now. In this study, we found that the expression of miR- 142 was obviously down-regulated in human cervical cancer tissues and a panel of cell lines. According to statistics, the expression of miR-142 was negatively related to advanced FIGO stage and lymphatic metastasis (p < 0.001). Furthermore, our functional analysis revealed the overexpression of miR-142 affected cell proliferation and invasiveness, and enhanced cell apoptosis in representative SiHa and HeLa cells. Based on the molecular level, our findings showed the 3′ untranslated region (3′-UTR) of high-mobility group box 1 protein (HMGB1) was a direct target of miR-142, and determined an inverse correlation with the expression of miR-142. Ectopic expression of HMGB1 could attenuate the inhibitory impact of miR-142 on the proliferation and invasiveness of cervical cancer cells. In conclusion, the present work suggested that miR-142 affects cervical cancer cell proliferation and invasiveness, and enhances cell apoptosis via directly targeting the expression of HMGB1, and these findings may lay a novel foundation for the promising therapy target of cervical cancer.
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Affiliation(s)
- Daqiong Jiang
- Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan 430071, Hubei, P.R. China
| | - Huiyan Wang
- Department of Gynecological Oncology, Hospital of Wuhan University of Technology, Wuhan 430070, Hubei, P.R. China
| | - Zhuyan Li
- Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan 430071, Hubei, P.R. China
| | - Zhen Li
- Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan 430071, Hubei, P.R. China
| | - Xin Chen
- Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan 430071, Hubei, P.R. China
| | - Hongbing Cai
- Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan 430071, Hubei, P.R. China
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Combination curcumin and (-)-epigallocatechin-3-gallate inhibits colorectal carcinoma microenvironment-induced angiogenesis by JAK/STAT3/IL-8 pathway. Oncogenesis 2017; 6:e384. [PMID: 28967875 PMCID: PMC5668882 DOI: 10.1038/oncsis.2017.84] [Citation(s) in RCA: 80] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 07/31/2017] [Accepted: 08/19/2017] [Indexed: 12/15/2022] Open
Abstract
Tumor microenvironment has a crucial role in cancer development and progression, whereas the mechanism of how it regulates angiogenesis is unclear. In this study, we simulated the colorectal carcinoma microenvironment by conditioned medium (CM) of colorectal carcinoma cell lines (SW620, HT-29, HCT116) supernatant or colorectal carcinoma tissue homogenate supernatant to induce normal endothelial cells (NECs). We found that colorectal carcinoma CM promoted tumor angiogenesis by coercing NECs toward tumor endothelial cells (TECs) with the activation of the JAK/STAT3 signaling pathway. Antibody array analysis showed HT-29 supernatant contained numerous angiogenesis-related proteins, especially IL-8. Interestingly, the production of IL-8 in NECs induced by HT-29 CM was also increased. We also verified the crucial role of IL-8 in promoting the CM-induced angiogenesis, as IL-8 repression by neutralizing antibody abolished the transition of NECs toward TECs. Curcumin and (-)-epigallocatechin-3-gallate (EGCG) are broadly investigated in cancer chemoprevention. However, poor bioavailability hurdles their application alone, and the mechanism of their anti-angiogenesis still need to be illuminated. Here, we found that curcumin combination with EGCG attenuated the tumor CM-induced transition of NECs toward TECs by inhibiting JAK/STAT3 signaling pathway. Furthermore, the combination of curcumin and EGCG markedly reduced tumor growth and angiogenesis in the colorectal carcinoma PDX mouse model, and the combined anti-angiogenic effect was better than that of curcumin or EGCG alone. Taken together, our findings provide a new mechanism of tumor angiogenesis, and the combination of curcumin and EGCG represents a potential anti-angiogenic therapeutic method for colorectal carcinoma.
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32
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Masuda T, Hayashi N, Kuroda Y, Ito S, Eguchi H, Mimori K. MicroRNAs as Biomarkers in Colorectal Cancer. Cancers (Basel) 2017; 9:cancers9090124. [PMID: 28902152 PMCID: PMC5615339 DOI: 10.3390/cancers9090124] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Revised: 09/01/2017] [Accepted: 09/10/2017] [Indexed: 12/11/2022] Open
Abstract
MicroRNAs (miRs) are small RNAs that repress mRNA translation, resulting in the degradation of mRNAs and regulation of the expression levels of various genes. Recent studies have shown that aberrant miR expression has a functional role in the initiation and progression of various malignancies, including colorectal cancer (CRC), which is one of the leading causes of cancer-related death worldwide. miRs have also been shown to have applications as diagnostic, prognostic, and predictive biomarkers because of their high tissue specificity, stability, and altered expression in tumor development. In this report, we examined the role of miRs as biomarkers in CRC through a review of meta-analyses and large-scale analyses having strong statistical confidence in the study outcomes. We also discuss current issues in the clinical application of these miRs.
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Affiliation(s)
- Takaaki Masuda
- Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
| | - Naoki Hayashi
- Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
| | - Yosuke Kuroda
- Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
| | - Shuhei Ito
- Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
| | - Hidetoshi Eguchi
- Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
| | - Koshi Mimori
- Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
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Qu Y, Liu H, Lv X, Liu Y, Wang X, Zhang M, Zhang X, Li Y, Lou Q, Li S, Li H. MicroRNA-16-5p overexpression suppresses proliferation and invasion as well as triggers apoptosis by targeting VEGFA expression in breast carcinoma. Oncotarget 2017; 8:72400-72410. [PMID: 29069797 PMCID: PMC5641140 DOI: 10.18632/oncotarget.20398] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Accepted: 08/07/2017] [Indexed: 01/08/2023] Open
Abstract
MicroRNAs (miRNAs), a class of small noncoding RNA molecules, can manipulate the expressions of endogenous tumor-related genes, and are implicated in the development and progression of a wide type of tumors. In this study, the investigation from real-time quantitative PCR revealed that miRNA-16-5p was downregulated in breast carcinoma tissues and cells, coupled with the elevations of HIF-α and VEGFA protein expressions, compared with normal tissues. Lentiviral armed with miR-16-5p markedly increased the miR-16-5p levels in MCF-7 and MDA-MB-231 cells, compared to blank and NC groups, and miR-16-5p overexpression significantly inhibited the proliferation and colony formation in MCF-7 and MDA-MB-231 cells. Besides, miR-16-5p upregulation markedly induced apoptosis and reduced invasion ability in MCF-7 and MDA-MB-231 cells. Notably, VEGFA was direct target of miR-16-5p. Stepwise investigation from in vitro and in vivo experiments demonstrated that miR-16-5p overexpression suppressed tumor growth and reduced HIF-α and VEGFA expressions in breast carcinoma cells and nude mice tumor tissues. These findings provide novel insights into molecular mechanism involved in the roles of miR-16-5p in tumor development and progression of breast carcinoma, and thus manipulation of miR-16-5p may be a novel potential therapeutic target for future therapies of the patients with breast carcinoma.
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Affiliation(s)
- Yunhui Qu
- Department of Pathology, School of Basic Medical Sciences, Zhengzhou University and The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, Henan, P.R. China.,Clinical Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, Henan, P.R. China
| | - Hongtao Liu
- Laboratory for Cell Biology, College of Life Sciences of Zhengzhou University, Zhengzhou, 450001, Henan, P.R. China
| | - Xinquan Lv
- Department of Pathology, School of Basic Medical Sciences, Zhengzhou University and The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, Henan, P.R. China
| | - Yuqiong Liu
- Department of Pathology, School of Basic Medical Sciences, Zhengzhou University and The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, Henan, P.R. China
| | - Xiaojuan Wang
- Department of Pathology, School of Basic Medical Sciences, Zhengzhou University and The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, Henan, P.R. China
| | - Min Zhang
- Department of Pathology, School of Basic Medical Sciences, Zhengzhou University and The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, Henan, P.R. China
| | - Xiaqing Zhang
- Laboratory for Cell Biology, College of Life Sciences of Zhengzhou University, Zhengzhou, 450001, Henan, P.R. China
| | - Yuenan Li
- Laboratory for Cell Biology, College of Life Sciences of Zhengzhou University, Zhengzhou, 450001, Henan, P.R. China
| | - Qianqian Lou
- Laboratory for Cell Biology, College of Life Sciences of Zhengzhou University, Zhengzhou, 450001, Henan, P.R. China
| | - Shenglei Li
- Department of Pathology, School of Basic Medical Sciences, Zhengzhou University and The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, Henan, P.R. China
| | - Huixiang Li
- Department of Pathology, School of Basic Medical Sciences, Zhengzhou University and The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, Henan, P.R. China
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Lin J, Chuang CC, Zuo L. Potential roles of microRNAs and ROS in colorectal cancer: diagnostic biomarkers and therapeutic targets. Oncotarget 2017; 8:17328-17346. [PMID: 28061475 PMCID: PMC5370044 DOI: 10.18632/oncotarget.14461] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Accepted: 12/16/2016] [Indexed: 02/06/2023] Open
Abstract
As one of the most commonly diagnosed cancers worldwide, colorectal adenocarcinoma often occurs sporadically in individuals aged 50 or above and there is an increase among younger patients under 50. Routine screenings are recommended for this age group to improve early detection. The multifactorial etiology of colorectal cancer consists of both genetic and epigenetic factors. Recently, studies have shown that the development and progression of colorectal cancer can be attributed to aberrant expression of microRNA. Reactive oxygen species (ROS) that play a key role in cancer cell survival, can also lead to carcinogenesis and cancer exacerbations. Given the rapid accumulating knowledge in the field, an updated review regarding microRNA and ROS in colorectal cancer is necessary. An extensive literature search has been conducted in PubMed/Medline databases to review the roles of microRNAs and ROS in colorectal cancer. Unique microRNA expression in tumor tissue, peripheral blood, and fecal samples from patients with colorectal cancer is outlined. Therapeutic approaches focusing on microRNA and ROS in colorectal cancer treatment is also delineated. This review aims to summarize the newest knowledge on the pathogenesis of colorectal cancer in the hopes of discovering novel diagnostic biomarkers and therapeutic techniques.
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Affiliation(s)
- Jingmei Lin
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Chia-Chen Chuang
- Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, Columbus, OH, USA.,Interdisciplinary Biophysics Graduate Program, The Ohio State University, Columbus, OH, USA
| | - Li Zuo
- Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, Columbus, OH, USA.,Interdisciplinary Biophysics Graduate Program, The Ohio State University, Columbus, OH, USA
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Garajová I, Ferracin M, Porcellini E, Palloni A, Abbati F, Biasco G, Brandi G. Non-Coding RNAs as Predictive Biomarkers to Current Treatment in Metastatic Colorectal Cancer. Int J Mol Sci 2017; 18:ijms18071547. [PMID: 28714940 PMCID: PMC5536035 DOI: 10.3390/ijms18071547] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Revised: 07/13/2017] [Accepted: 07/14/2017] [Indexed: 12/22/2022] Open
Abstract
The onset and selection of resistant clones during cancer treatment with chemotherapy or targeted therapy is a major issue in the clinical management of metastatic colorectal cancer patients. It is possible that a more personalized treatment selection, using reliable response-to-therapy predictive biomarkers, could lead to an improvement in the success rate of the proposed therapies. Although the process of biomarker selection and validation could be a long one, requiring solid statistics, large cohorts and multicentric validations, non-coding RNAs (ncRNAs) and in particular microRNAs, proved to be extremely promising in this field. Here we summarize some of the main studies correlating specific ncRNAs with sensitivity/resistance to chemotherapy, anti-VEGF therapy, anti-EGFR therapy and immunotherapy in colorectal cancer (CRC).
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Affiliation(s)
- Ingrid Garajová
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Sant'Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy.
- Interdepartmental Centre of Cancer Research "Giorgio Prodi", University of Bologna, 40138 Bologna, Italy.
| | - Manuela Ferracin
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Sant'Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy.
| | - Elisa Porcellini
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Sant'Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy.
| | - Andrea Palloni
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Sant'Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy.
| | - Francesca Abbati
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Sant'Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy.
| | - Guido Biasco
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Sant'Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy.
- Interdepartmental Centre of Cancer Research "Giorgio Prodi", University of Bologna, 40138 Bologna, Italy.
| | - Giovanni Brandi
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Sant'Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy.
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Exosome-encapsulated microRNAs as circulating biomarkers for colorectal cancer. Oncotarget 2017; 8:60149-60158. [PMID: 28947960 PMCID: PMC5601128 DOI: 10.18632/oncotarget.18557] [Citation(s) in RCA: 101] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Accepted: 06/08/2017] [Indexed: 02/06/2023] Open
Abstract
Currently available studies have suggested that a number of exosome-encapsulated microRNAs (miRNAs) are recognized as stable biomarkers for cancers. However, little is known about the effect of exosomal miRNAs on colorectal cancer (CRC). The aim of study is to identify specific miRNAs in serum exosomes, which may serve as potential diagnostic and prognostic biomarkers and therapeutic targets for CRC. Microarray analyses of miRNAs in serum exosomes from 3 primary CRC patients and 3 healthy controls were performed. Those differentially expressed exosome-encapsulated miRNAs were verified in exosome-enriched serum samples from 77 CRC patients and 20 healthy controls by quantitative real-time PCR (qRT-PCR). A total of 39 aberrantly expressed miRNAs in serum exosomes were identified by microarray analysis. After confirmation by qRT-PCR, we found that 5 exosome-encapsulated miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p and miR-548c-5p) were significantly down-regulated, while 2 exosome-encapsulated miRNAs (miR-486-5p and miR-3180-5p) were significantly up-regulated in serum. Decreased levels of miR-638 in serum exosomes were associated with increased risk of liver metastasis and later TNM stage of CRC. Networks analyses revealed that 5 aberrantly expressed miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p, and miR-548c-5p) might be involved in the process of glucose metabolism in CRC. The present study shows the specific serum profile of exosome-encapsulated miRNAs in CRC. Those specific miRNAs in serum exosomes may serve as disease biomarkers and novel therapeutic targets for CRC.
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Colorectal Cancer: From the Genetic Model to Posttranscriptional Regulation by Noncoding RNAs. BIOMED RESEARCH INTERNATIONAL 2017; 2017:7354260. [PMID: 28573140 PMCID: PMC5442347 DOI: 10.1155/2017/7354260] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 02/16/2017] [Indexed: 12/11/2022]
Abstract
Colorectal cancer is the third most common form of cancer in developed countries and, despite the improvements achieved in its treatment options, remains as one of the main causes of cancer-related death. In this review, we first focus on colorectal carcinogenesis and on the genetic and epigenetic alterations involved. In addition, noncoding RNAs have been shown to be important regulators of gene expression. We present a general overview of what is known about these molecules and their role and dysregulation in cancer, with a special focus on the biogenesis, characteristics, and function of microRNAs. These molecules are important regulators of carcinogenesis, progression, invasion, angiogenesis, and metastases in cancer, including colorectal cancer. For this reason, miRNAs can be used as potential biomarkers for diagnosis, prognosis, and efficacy of chemotherapeutic treatments, or even as therapeutic agents, or as targets by themselves. Thus, this review highlights the importance of miRNAs in the development, progression, diagnosis, and therapy of colorectal cancer and summarizes current therapeutic approaches for the treatment of colorectal cancer.
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Kuroda K, Fukuda T, Krstic-Demonacos M, Demonacos C, Okumura K, Isogai H, Hayashi M, Saito K, Isogai E. miR-663a regulates growth of colon cancer cells, after administration of antimicrobial peptides, by targeting CXCR4-p21 pathway. BMC Cancer 2017; 17:33. [PMID: 28061765 PMCID: PMC5219750 DOI: 10.1186/s12885-016-3003-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Accepted: 12/15/2016] [Indexed: 01/18/2023] Open
Abstract
Background Antimicrobial peptides (AMPs) play important roles in the innate immune system of all life forms and recently have been characterized as multifunctional peptides that have a variety of biological roles such as anticancer agents. However, detailed mechanism of antimicrobial peptides on cancer cells is still largely unknown. Methods miRNA array and real-time qPCR were performed to reveal the behavior of miRNA in colon cancer HCT116 cells during the growth suppression induced by the AMPs. Establishment of miR-663a over-expressing HCT116 cells was carried out for the evaluation of growth both in vitro and in vivo. To identify the molecular mechanisms, we used western blotting analysis. Results miR-663a is upregulated by administration of the human cathelicidin AMP, LL-37, and its analogue peptide, FF/CAP18, in the colon cancer cell line HCT116. Over-expression of miR-663a caused anti-proliferative effects both in vitro and in vivo. We also provide evidence supporting the view that these effects are attributed to suppression of the expression of the chemokine receptor CXCR4, resulting in the abrogation of phosphorylation of Akt and cell cycle arrest in G2/M via p21 activation. Conclusions This study contributes to the understanding of the AMPs’ mediated anti-cancer mechanisms in colon cancer cells and highlights the possibility of using AMPs and miRNAs towards developing future strategies for cancer therapy. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-3003-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Kengo Kuroda
- Laboratory of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan
| | - Tomokazu Fukuda
- United Graduate School of Agricultural Sciences, Graduate School of Agricultural Science, Iwate University, Morioka, Iwate, Japan
| | | | - Constantinos Demonacos
- Division of Pharmacy and Optometry, Faculty of Biology Medicine and Health, School of Health Sciences, University of Manchester, Manchester, UK
| | - Kazuhiko Okumura
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido, Japan
| | - Hiroshi Isogai
- Animal Research Center, Sapporo Medical University, Sapporo, Japan
| | - Miwa Hayashi
- Laboratory of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan
| | - Kazuki Saito
- Laboratory of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan
| | - Emiko Isogai
- Laboratory of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan.
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Li SC, Vu LT, Luo JJ, Zhong JF, Li Z, Dethlefs BA, Loudon WG, Kabeer MH. Tissue Elasticity Bridges Cancer Stem Cells to the Tumor Microenvironment Through microRNAs: Implications for a "Watch-and-Wait" Approach to Cancer. Curr Stem Cell Res Ther 2017; 12:455-470. [PMID: 28270089 PMCID: PMC5587377 DOI: 10.2174/1574888x12666170307105941] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2016] [Revised: 02/01/2017] [Accepted: 03/01/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND Targeting the tumor microenvironment (TME) through which cancer stem cells (CSCs) crosstalk for cancer initiation and progression, may open new treatments different from those centered on the original hallmarks of cancer genetics thereby implying a new approach for suppression of TME driven activation of CSCs. Cancer is dynamic, heterogeneous, evolving with the TME and can be influenced by tissue-specific elasticity. One of the mediators and modulators of the crosstalk between CSCs and mechanical forces is miRNA, which can be developmentally regulated, in a tissue- and cellspecific manner. OBJECTIVE Here, based on our previous data, we provide a framework through which such gene expression changes in response to external mechanical forces can be understood during cancer progression. Recognizing the ways mechanical forces regulate and affect intracellular signals with applications in cancer stem cell biology. Such TME-targeted pathways shed new light on strategies for attacking cancer stem cells with fewer side effects than traditional gene-based treatments for cancer, requiring a "watchand- wait" approach. We attempt to address both normal brain microenvironment and tumor microenvironment as both works together, intertwining in pathology and physiology - a balance that needs to be maintained for the "watch-and-wait" approach to cancer. CONCLUSION This review connected the subjects of tissue elasticity, tumor microenvironment, epigenetic of miRNAs, and stem-cell biology that are very relevant in cancer research and therapy. It attempts to unify apparently separate entities in a complex biological web, network, and system in a realistic and practical manner, i.e., to bridge basic research with clinical application.
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Affiliation(s)
- Shengwen Calvin Li
- Neuro-Oncology and Stem Cell Research Laboratory, Center for Neuroscience Research, CHOC Children’s Hospital Research Institute, 1201 West La Veta Ave., Orange, CA 92868, USA
- Department of Neurology, University of California-Irvine School of Medicine, Orange, CA 92697-4292, USA
- Department of Biological Science, California State University, Fullerton, CA 92834, USA
| | - Long T. Vu
- Neuro-Oncology and Stem Cell Research Laboratory, Center for Neuroscience Research, CHOC Children’s Hospital Research Institute, 1201 West La Veta Ave., Orange, CA 92868, USA
- Department of Biological Science, California State University, Fullerton, CA 92834, USA
| | | | - Jiang F. Zhong
- Division of Periodontology, Diagnostic Sciences & Dental Hygiene and Biomedical Sciences, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90089, USA
| | - Zhongjun Li
- Division of Periodontology, Diagnostic Sciences & Dental Hygiene and Biomedical Sciences, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90089, USA
- Division of Radiation Biology, Department of Blood Transfusion, The Second Affiliated Hospital, Third Military Medical University, Xinqiao Road, Shapingba, Chongqing 400037, China
| | - Brent A Dethlefs
- Neuro-Oncology and Stem Cell Research Laboratory, Center for Neuroscience Research, CHOC Children’s Hospital Research Institute, 1201 West La Veta Ave., Orange, CA 92868, USA
| | - William G. Loudon
- Neuro-Oncology and Stem Cell Research Laboratory, Center for Neuroscience Research, CHOC Children’s Hospital Research Institute, 1201 West La Veta Ave., Orange, CA 92868, USA
- Department of Biological Science, California State University, Fullerton, CA 92834, USA
- Division of Radiation Biology, Department of Blood Transfusion, The Second Affiliated Hospital, Third Military Medical University, Xinqiao Road, Shapingba, Chongqing 400037, China
- Department of Neurological Surgery, Saint Joseph Hospital, Orange, CA 92868, USA
- Department of Neurological Surgery, University of California-Irvine School of Medicine, Orange, CA 92862, USA
| | - Mustafa H. Kabeer
- Neuro-Oncology and Stem Cell Research Laboratory, Center for Neuroscience Research, CHOC Children’s Hospital Research Institute, 1201 West La Veta Ave., Orange, CA 92868, USA
- Department of Pediatric Surgery, CHOC Children’s Hospital, 1201 West La Veta Ave., Orange, CA 92868, USA
- Department of Surgery, University of California-Irvine School of Medicine, 333 City Blvd. West, Suite 700, Orange, CA 92868, USA
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Wang F, Li P, Feng Y, Hu YL, Liu YF, Guo YB, Jiang XL, Mao QS, Xue WJ. Low expression of RASSF10 is associated with poor survival in patients with colorectal cancer. Hum Pathol 2016; 62:108-114. [PMID: 28041974 DOI: 10.1016/j.humpath.2016.12.016] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Revised: 12/06/2016] [Accepted: 12/15/2016] [Indexed: 12/01/2022]
Abstract
The RASSF10 has been identified as a tumor suppressor in human colorectal cancer (CRC). However, the expression of RASSF10 in patients with CRC has not been evaluated for its potential use as a biomarker in the diagnosis and prognosis assessment of CRC. We analyzed the expression of RASSF10 mRNA (n=30) and protein (n=205) in CRC and matched noncancerous colon tissue samples to explore the relationships among RASSF10 expression, clinicopathological factors, and prognosis in patients with CRC. Our results showed that the expression of RASSF10 mRNA and protein in CRC-adjacent tissues was higher than that in CRC tissues. Low RASSF10 expression was associated with the T stage (P=.037, odds ratio, 0.664; 95% confidence interval, 0.452-0.975) and the N stage (P<.001, odds ratio, 0.318; 95% confidence interval, 0.184-0.549) of the tumors. In addition, univariate analysis revealed that patients with CRC with lower RASSF10 expression had poorer overall survival (OS; P<.001) and disease-free survival (DFS; P<.001). The 5-year OS and DFS rates were 48.2% and 28.3%, respectively, in patients with low RASSF10 expression and 82.2% and 62.6%, respectively, in patients with high RASSF10 expression. Multivariate Cox regression analysis revealed that the strongest predictors of OS and DFS were RASSF10 expression (P<.001 and P<.001, respectively), T stage (P=.003 and P=.009, respectively), and N stage (P=.005 and P=.026, respectively). These results demonstrate that low expression of RASSF10 in CRC tissues is significantly correlated with poor survival after curative resection and may serve as a useful biomarker predictive of CRC prognosis.
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Affiliation(s)
- Fei Wang
- Department of General Surgery, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China; Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China
| | - Peng Li
- Department of General Surgery, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China
| | - Ying Feng
- Department of General Surgery, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China
| | - Yi-Lin Hu
- Department of General Surgery, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China
| | - Yi-Fei Liu
- Department of Pathology, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China
| | - Yi-Bing Guo
- Department of Surgical Comprehensive Laboratory, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China
| | - Xin-Lin Jiang
- Department of General Surgery, Hospital of Traditional Chinese Medicine of Nantong City, Nantong, Jiangsu 226001, China
| | - Qin-Sheng Mao
- Department of General Surgery, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China.
| | - Wan-Jiang Xue
- Department of General Surgery, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China.
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Wang J, Liu H, Tian L, Wang F, Han L, Zhang W, Bai YA. miR-15b Inhibits the Progression of Glioblastoma Cells Through Targeting Insulin-like Growth Factor Receptor 1. Discov Oncol 2016; 8:49-57. [PMID: 27896672 DOI: 10.1007/s12672-016-0276-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 11/21/2016] [Indexed: 12/13/2022] Open
Abstract
The microRNAs (miRNAs) have been suggested as a tumor suppressor in recent years. miR-15b was reported to exert an anti-oncogenic role in the proliferation, migration, and invasion of diverse tumor cells. However, the mechanisms underlying miR-15b-mediated biology of glioblastoma are still unclear. In the present study, the expression of miR-15b was down-regulated in glioblastoma tumor tissues and U87 and U251 cells, but insulin-like growth factor receptor 1 (IGF1R) expression became up-regulated in these tumor tissues and cells (all p < 0.001). Furthermore, IGF1R expression was inversely associated with miR-15b expression. Notably, patients with lower miR-15b expression have a much shorter survival period compared with high expression (log-rank test p = 0.045). In vitro data demonstrated that miR-15b mimics inhibited the proliferation, cell cycle arrest, and invasion of U87 and U251 cells. Besides, we validated IGF1R as a direct target of miR-15b using dual luciferase assays, and IGF1R plasmids partially abrogated miR-15b mimics inhibited cell proliferation. In vivo, miR-15b mimics indeed repressed cell proliferation in mouse xenograft model. In conclusion, our study demonstrated that miR-15b inhibits the progression of glioblastoma cells through targeting IGF1R, and miR-15b can be recommended as a tumor suppressor in the progression of glioblastoma.
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Affiliation(s)
- Jian Wang
- Department of Neurosurgery, Weifang Yidu Central Hospital, No. 4138, Linglongshan Road, Qingzhou, Shandong, 262500, China
| | - Huaqiang Liu
- Department of Neurosurgery, Weifang Yidu Central Hospital, No. 4138, Linglongshan Road, Qingzhou, Shandong, 262500, China
| | - Lin Tian
- Department of Neurosurgery, Weifang Yidu Central Hospital, No. 4138, Linglongshan Road, Qingzhou, Shandong, 262500, China
| | - Fachen Wang
- Department of Neurosurgery, Weifang Yidu Central Hospital, No. 4138, Linglongshan Road, Qingzhou, Shandong, 262500, China
| | - Liangbo Han
- Department of Neurosurgery, Weifang Yidu Central Hospital, No. 4138, Linglongshan Road, Qingzhou, Shandong, 262500, China
| | - Wei Zhang
- Department of Neurosurgery, Weifang Yidu Central Hospital, No. 4138, Linglongshan Road, Qingzhou, Shandong, 262500, China
| | - Yun-An Bai
- Department of Neurosurgery, Weifang Yidu Central Hospital, No. 4138, Linglongshan Road, Qingzhou, Shandong, 262500, China.
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Jili S, Eryong L, Lijuan L, Chao Z. RUNX3 inhibits laryngeal squamous cell carcinoma malignancy under the regulation of miR-148a-3p/DNMT1 axis. Cell Biochem Funct 2016; 34:597-605. [PMID: 27859417 DOI: 10.1002/cbf.3233] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Revised: 10/07/2016] [Accepted: 10/07/2016] [Indexed: 01/05/2023]
Affiliation(s)
- Su Jili
- Department of Otorhinolaryngology, Head and Neck Surgery; The first Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology; Luoyang 471003 China
| | - Lu Eryong
- Department of Otorhinolaryngology, Head and Neck Surgery; The first Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology; Luoyang 471003 China
| | - Lu Lijuan
- Department of Obstetrics and Gynecology; The first Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology; Luoyang 471003 China
| | - Zhang Chao
- Department of Otorhinolaryngology, Head and Neck Surgery; The first Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology; Luoyang 471003 China
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Saberi A, Shahbazi-Gahrouei D, Abbasian M, Fesharaki M, Baharlouei A, Arab-Bafrani Z. Gold nanoparticles in combination with megavoltage radiation energy increased radiosensitization and apoptosis in colon cancer HT-29 cells. Int J Radiat Biol 2016; 93:315-323. [DOI: 10.1080/09553002.2017.1242816] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Alihossein Saberi
- Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Daryoush Shahbazi-Gahrouei
- Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mahdi Abbasian
- Department of Biotechnology, College of Agriculture, Isfahan University of Technology, Isfahan, Iran
- Stem Cell Research Center, Golestan University of Medical Science, Gorgan, Iran
| | - Mehrafarin Fesharaki
- Department of Cell Sciences Research Center Medical Science, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Azam Baharlouei
- Department of Biotechnology, College of Agriculture, Isfahan University of Technology, Isfahan, Iran
| | - Zahra Arab-Bafrani
- Stem Cell Research Center, Golestan University of Medical Science, Gorgan, Iran
- Department of Medical Physics, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
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Hao W, Luo W, Bai M, Li J, Bai X, Guo J, Wu J, Wang M. MicroRNA-206 Inhibited the Progression of Glioblastoma Through BCL-2. J Mol Neurosci 2016; 60:531-538. [PMID: 27558109 DOI: 10.1007/s12031-016-0824-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2016] [Accepted: 08/17/2016] [Indexed: 12/21/2022]
Abstract
Gliomas are the most common type of brain tumor and have a poor prognosis. MicroRNAs (miRNAs) are a class of small, endogenous, and non-coding RNAs that play crucial roles in cell proliferation, survival, and invasion. Deregulated expression of miR-206 has been investigated in many cancers. However, the role of miR-206 in glioblastoma is still unclear. In the present study, we found that the expression of miR-206 was decreased in cancer tissues compared with normal tissues. However, the expression level of BCL-2 was higher in cancer tissues than that in normal tissues (all p < 0.001). Statistically, the expression level of BCL-2 was inversely correlated with the miR-206. In addition, the overall survival of glioblastoma patients with lower miR-206 expression was significantly shorter than those with high miR-206 expression (p < 0.001). Besides, the expression of miR-206 was also decreased in U87 and U251 cells. In vitro assays showed that ectopic miR-206 expression affected the proliferation, cell cycle, and invasion in U87 and U251 cells. Importantly, we identified BCL-2 as a direct target of miR-206 in U87 and U251 cells using luciferase assay. Overexpression of BCL-2 partially attenuated the miR-206-mediated cell proliferation. In vivo, overexpression of miR-206 suppressed the progression of glioblastoma cells using mice xenograft model. In conclusion, this study suggested that miR-206 could act as a tumor suppressor gene through inhibiting BCL-2 in the development of glioblastoma.
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Affiliation(s)
- Wenjiong Hao
- Department of Neurosurgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China.,Department of Neurosurgery, Affiliated Hospital, Medical College of Yan'an University, Yan'an City, Shaanxi, 716000, People's Republic of China
| | - Wei Luo
- Department of Neurosurgery, The Affiliated Hospital of Shaanxi Traditional Chinese Medicine University, Xianyang, 712000, People's Republic of China
| | - Mangmang Bai
- Department of Neurosurgery, Affiliated Hospital, Medical College of Yan'an University, Yan'an City, Shaanxi, 716000, People's Republic of China
| | - Jian Li
- Department of Neurosurgery, Affiliated Hospital, Medical College of Yan'an University, Yan'an City, Shaanxi, 716000, People's Republic of China
| | - Xiaobin Bai
- Department of Neurosurgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China
| | - Jie Guo
- Department of Neurosurgery, Affiliated Hospital, Medical College of Yan'an University, Yan'an City, Shaanxi, 716000, People's Republic of China
| | - Jinsong Wu
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China
| | - Maode Wang
- Department of Neurosurgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China.
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