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1
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Saputra HA, Karim MM. Fundamentals and research progression on electrochemical sensing of colorectal cancer. Mikrochim Acta 2025; 192:355. [PMID: 40369291 DOI: 10.1007/s00604-025-07207-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Accepted: 04/30/2025] [Indexed: 05/16/2025]
Abstract
Colorectal cancer (CRC) is a type of malignant disease that affects the large intestine (colon) and rectum. The CRC is among the causes of the highest mortality rates worldwide, so its rapid and sensitive early diagnosis is substantial. In the last few decades, CRC detection by electrochemical biosensors has progressed significantly due to their amenability and cost-effectiveness. Various electrochemical sensing strategies have been implemented, involving CRC biomarkers, such as protein, gene, or even CRC cells, that play a crucial role in screening tests, treatment, and prognosis. Electrochemical sensors are favored in this regard, owing to their ability to provide real-time, on-site detection with a straightforward preparation of samples. The present work provides an overview from the basic concepts to the recent research advances in electrochemical CRC biosensors for the management of patients. The review covers the importance of CRC detection, an introduction to electrochemical sensors, and cutting-edge electrochemical CRC biosensors. Further, challenges, limitations, and future research directions in developing and applying electrochemical sensing tools for CRC biomarkers are also comprehensively discussed. By consolidating the current research status, the present work aims to inspire further innovation in the development of electrochemical CRC biosensors. The insights presented here are expected to contribute to advancing more efficient, accessible diagnostic devices for CRC in the future.
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Affiliation(s)
| | - Md Mobarok Karim
- Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
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2
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Gondal MN, Farooqi HMU. Single-Cell Transcriptomic Approaches for Decoding Non-Coding RNA Mechanisms in Colorectal Cancer. Noncoding RNA 2025; 11:24. [PMID: 40126348 PMCID: PMC11932299 DOI: 10.3390/ncrna11020024] [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: 12/20/2024] [Revised: 01/27/2025] [Accepted: 03/03/2025] [Indexed: 03/25/2025] Open
Abstract
Non-coding RNAs (ncRNAs) play crucial roles in colorectal cancer (CRC) development and progression. Recent developments in single-cell transcriptome profiling methods have revealed surprising levels of expression variability among seemingly homogeneous cells, suggesting the existence of many more cell types than previously estimated. This review synthesizes recent advances in ncRNA research in CRC, emphasizing single-cell bioinformatics approaches for their analysis. We explore computational methods and tools used for ncRNA identification, characterization, and functional prediction in CRC, with a focus on single-cell RNA sequencing (scRNA-seq) data. The review highlights key bioinformatics strategies, including sequence-based and structure-based approaches, machine learning applications, and multi-omics data integration. We discuss how these computational techniques can be applied to analyze differential expression, perform functional enrichment, and construct regulatory networks involving ncRNAs in CRC. Additionally, we examine the role of bioinformatics in leveraging ncRNAs as diagnostic and prognostic biomarkers for CRC. We also discuss recent scRNA-seq studies revealing ncRNA heterogeneity in CRC. This review aims to provide a comprehensive overview of the current state of single-cell bioinformatics in ncRNA CRC research and outline future directions in this rapidly evolving field, emphasizing the integration of computational approaches with experimental validation to advance our understanding of ncRNA biology in CRC.
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Affiliation(s)
- Mahnoor Naseer Gondal
- Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA;
- Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Hafiz Muhammad Umer Farooqi
- Laboratory of Energy Metabolism, Division of Metabolic Disorders, Children’s Hospital of Orange County, Orange, CA 92868, USA
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Mohammadpour S, Noukabadi FN, Esfahani AT, Kazemi F, Esmaeili S, Zafarjafarzadeh N, Sarpash S, Nazemalhosseini-Mojarad E. Non-coding RNAs in Precursor Lesions of Colorectal Cancer: Their Role in Cancer Initiation and Formation. Curr Mol Med 2024; 24:565-575. [PMID: 37226783 DOI: 10.2174/1566524023666230523155719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 04/01/2023] [Accepted: 04/04/2023] [Indexed: 05/26/2023]
Abstract
Colorectal cancer (CRC) is one of the world's most common types of malignancy. The proliferation of precancerous lesions causes this type of cancer. Two distinct pathways for CRC carcinogenesis have been identified: the conventional adenoma-carcinoma pathway and the serrated neoplasia pathway. Recently, evidence has demonstrated the regulatory roles of noncoding RNAs (ncRNAs) in the initiation and progression of precancerous lesions, especially in the adenoma-carcinoma pathway and serrated neoplasia pathway. By expanding the science of molecular genetics and bioinformatics, several studies have identified dysregulated ncRNAs that function as oncogenes or tumor suppressors in cancer initiation and formation by diverse mechanisms via intracellular signaling pathways known to act on tumor cells. However, many of their roles are still unclear. This review summarizes the functions and mechanisms of ncRNAs (such as long non-coding RNAs, microRNAs, long intergenic non-coding RNAs, small interfering RNAs, and circRNAs) in the initiation and formation of precancerous lesions.
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Affiliation(s)
- Somayeh Mohammadpour
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences. Tehran, Iran
| | - Fatemeh Naderi Noukabadi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences. Tehran, Iran
| | - Amir Torshizi Esfahani
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences. Tehran, Iran
| | - Fatemeh Kazemi
- Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Medical Sciences, Islamic Azad University Tehran, Tehran, Iran
| | - Sahar Esmaeili
- Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Medical Sciences, Islamic Azad University Tehran, Tehran, Iran
| | - Nikta Zafarjafarzadeh
- Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Medical Sciences, Islamic Azad University Tehran, Tehran, Iran
| | - SeyedKasra Sarpash
- Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Medical Sciences, Islamic Azad University Tehran, Tehran, Iran
| | - Ehsan Nazemalhosseini-Mojarad
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Wanram S, Klaewkla N, Pinyosri P. Downregulation of Serum miR-133b and miR-206 Associate with Clinical Outcomes of Progression as Monitoring Biomarkers for Metastasis Colorectal Cancer Patients. Microrna 2024; 13:56-62. [PMID: 38231064 PMCID: PMC11275315 DOI: 10.2174/0122115366266024240101075745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 11/10/2023] [Accepted: 11/16/2023] [Indexed: 01/18/2024]
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most common cancer in the world. Noncoding RNAs or microRNAs (miRNAs; miRs) biomarkers can play a role in cancer carcinogenesis and progression. Specific KRAS and EGFR mutation are associated with CRC development playing a role in controlling the cellular process as epigenetic events. Circulating serum miRs can serve for early diagnosis, monitoring, and prognosis of CRC as biomarkers but it is still unclear, clinically. OBJECTIVE To determine potential biomarkers of circulating serum miR-133b and miR-206 in CRC patients Methods: Bioinformatic prediction of microRNA was screened followed by TargetScanHuman7.2, miRTar2GO, miRDB, MiRanda, and DIANA-microT-CDS. Forty-four CRC serum (19 locally advanced, 23 distant advanced CRC) and 12 normal serum samples were subsequently extracted for RNA isolation, cDNA synthesis, and miR validation. The candidate circulating serum miR-133b and miR-206 were validated resulting in a relative expression via quantitative RT-PCR. Relative expression was normalized to the spike-internal control and compared to normal samples as 1 using the -2ΔΔCt method in principle. RESULTS Our results represented 9 miRs of miR-206, miR-155-5p, miR-143-3p, miR-193a-3p, miR-30a- 5p, miR-30d-5p, miR-30e-5p, miR-543, miR-877-5p relate to KRAS-specific miRs, whereas, 9 miRs of miR-133b, miR-302a-3p, miR-302b-3p, miR-302d-3p, miR-302e, miR-520a-3p, miR-520b, miR-520c- 3p and miR-7-5p relevance to EGFR-specific miRs by using the bioinformatic prediction tools. Our results showed a decreased expression level of circulating serum miR-133b as well as miR-206 associating with CRC patients (local and advanced metastasis) when compared to normal (P < 0.05), significantly. CONCLUSION The circulating serum miR-133b and miR-206 can serve as significant biomarkers for monitoring the clinical outcome of progression with metastatic CRC patients. Increased drug-responsive CRC patients associated with crucial molecular intervention should be further explored, clinically.
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Affiliation(s)
- Surasak Wanram
- College of Medicine and Public Health, Ubon Ratchathani University, Ubon Ratchathani, 34190, Thailand
- Biomedical Science Research Unit, Ubon Ratchathani University, Ubon Ratchathani, 34190, Thailand
| | - Namphon Klaewkla
- College of Medicine and Public Health, Ubon Ratchathani University, Ubon Ratchathani, 34190, Thailand
| | - Parichart Pinyosri
- Biomedical Science Research Unit, Ubon Ratchathani University, Ubon Ratchathani, 34190, Thailand
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Bagheri R, Ghorbian M, Ghorbian S. Tumor circulating biomarkers in colorectal cancer. Cancer Treat Res Commun 2023; 38:100787. [PMID: 38194840 DOI: 10.1016/j.ctarc.2023.100787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 12/11/2023] [Accepted: 12/21/2023] [Indexed: 01/11/2024]
Abstract
CRC is a major global health concern and is responsible for a significant number of cancer-related deaths each year. The successful treatment of CRC becomes more difficult when it goes undetected until it has advanced to a later stage. Diagnostic biomarkers can play a critical role in the early detection of CRC, which leads to improved patient outcomes and increased survival rates. It is important to develop reliable biomarkers for the early detection of CRC to enable timely diagnosis and treatment. To date, CRC detection methods such as endoscopy, blood, and stool tests are imperfect and often only identify cases in the later stages of the disease. To overcome these limitations, researchers are turning to molecular biomarkers as a promising avenue for improving CRC detection. Diagnostic information can be provided more reliably through a noninvasive approach using biomarkers such as mRNA, circulating cell-free DNA, micro-RNA, long non-coding RNA, and proteins. These biomarkers can be found in blood, tissue, feces, and volatile organic compounds. The identification of molecular biomarkers with high sensitivity and specificity for early detection of CRC that are safe, cost-effective, and easily measurable remains a significant challenge for researchers. In this article, we will explore the latest advancements in blood-based diagnostic biomarkers for CRC and their potential impact on improving patient survival rates.
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Affiliation(s)
- Raana Bagheri
- Department of Molecular Genetics, Ahar Branch, Islamic Azad University, Ahar, Iran
| | - Mohsen Ghorbian
- Department of Computer Engineering, Qom Branch, Islamic Azad University, Qom, Iran
| | - Saeid Ghorbian
- Department of Molecular Genetics, Ahar Branch, Islamic Azad University, Ahar, Iran.
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Wang H, Cai G, Yu F, Li D, Wang C, Ma D, Han X, Chen J, Wang C, He J. Changes in the small noncoding RNA transcriptome in osteosarcoma cells. J Orthop Surg Res 2023; 18:898. [PMID: 38001513 PMCID: PMC10675919 DOI: 10.1186/s13018-023-04362-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Accepted: 11/08/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND Osteosarcoma has the highest incidence among bone malignant tumors and mainly occurs in adolescents and the elderly, but the pathological mechanism is still unclear, which makes early diagnosis and treatment very difficult. Bone marrow mesenchymal stem cells (BMSCs) are considered to be one of the sources of osteosarcoma cells. Therefore, a full understanding of the gene expression differences between BMSCs and osteosarcoma cells is very important to explore the pathogenesis of osteosarcoma and facilitate the early diagnosis and treatment of osteosarcoma. Small noncoding RNAs (sncRNAs) are a class of RNAs that do not encode proteins but directly play biological functions at the RNA level. SncRNAs mainly include Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), repeat RNAs and microRNAs (miRNAs). METHODS In this study, we compared the expression of sncRNAs in BMSCs and osteosarcoma cells by high-throughput sequencing and qPCR and looked for differentially expressed sncRNAs. CCK-8, clone formation and transwell assay were used to detect the effect of sncRNA in MG63 cells. RESULTS We found that 66 piRNAs were significantly upregulated and 70 piRNAs were significantly downregulated in MG63 cells. As for snoRNAs, 71 snoRNAs were significantly upregulated and 117 snoRNAs were significantly downregulated in MG63 cells. As for snRNAs, 35 snRNAs were significantly upregulated and 17 snRNAs were significantly downregulated in MG63 cells. As for repeat RNAs, 6 repeat RNAs were significantly upregulated and 7 repeat RNAs were significantly downregulated in MG63 cells. As for miRNAs, 326 miRNAs were significantly upregulated and 281 miRNAs were significantly downregulated in MG63 cells. Overexpression of piRNA DQ596225, snoRNA ENST00000364830.2, snRNA ENST00000410533.1 and miRNA hsa-miR-369-5p inhibited the proliferation and migration of MG63 cells. CONCLUSIONS Our results provide a theoretical basis for the pathogenesis, early diagnosis and treatment of osteosarcoma.
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Affiliation(s)
- Hui Wang
- Department of Orthopedic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, People's Republic of China
| | - Guiquan Cai
- Department of Orthopedic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, People's Republic of China
| | - Fengbin Yu
- Department of Orthopaedics, The 72nd Group Army Hospital of PLA, Huzhou, 313000, Zhejiang, People's Republic of China
| | - De Li
- Department of Orthopedic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, People's Republic of China
| | - Chenglong Wang
- Department of Orthopedic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, People's Republic of China
| | - Ding Ma
- Department of Orthopedic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, People's Republic of China
| | - Xiuguo Han
- Department of Orthopedic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, People's Republic of China
| | - Jiajia Chen
- Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China
| | - Chuandong Wang
- Department of Orthopedic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, People's Republic of China.
| | - Jiye He
- Department of Orthopedic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, People's Republic of China.
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Islam MS, Gopalan V, Lam AK, Shiddiky MJA. Current advances in detecting genetic and epigenetic biomarkers of colorectal cancer. Biosens Bioelectron 2023; 239:115611. [PMID: 37619478 DOI: 10.1016/j.bios.2023.115611] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 08/07/2023] [Accepted: 08/16/2023] [Indexed: 08/26/2023]
Abstract
Colorectal carcinoma (CRC) is the third most common cancer in terms of diagnosis and the second in terms of mortality. Recent studies have shown that various proteins, extracellular vesicles (i.e., exosomes), specific genetic variants, gene transcripts, cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and altered epigenetic patterns, can be used to detect, and assess the prognosis of CRC. Over the last decade, a plethora of conventional methodologies (e.g., polymerase chain reaction [PCR], direct sequencing, enzyme-linked immunosorbent assay [ELISA], microarray, in situ hybridization) as well as advanced analytical methodologies (e.g., microfluidics, electrochemical biosensors, surface-enhanced Raman spectroscopy [SERS]) have been developed for analyzing genetic and epigenetic biomarkers using both optical and non-optical tools. Despite these methodologies, no gold standard detection method has yet been implemented that can analyze CRC with high specificity and sensitivity in an inexpensive, simple, and time-efficient manner. Moreover, until now, no study has critically reviewed the advantages and limitations of these methodologies. Here, an overview of the most used genetic and epigenetic biomarkers for CRC and their detection methods are discussed. Furthermore, a summary of the major biological, technical, and clinical challenges and advantages/limitations of existing techniques is also presented.
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Affiliation(s)
- Md Sajedul Islam
- Cancer Molecular Pathology, School of Medicine & Dentistry, Griffith University, Gold Coast Campus, Southport, QLD, 4222, Australia; Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, 4222, Australia
| | - Vinod Gopalan
- Cancer Molecular Pathology, School of Medicine & Dentistry, Griffith University, Gold Coast Campus, Southport, QLD, 4222, Australia; Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, 4222, Australia.
| | - Alfred K Lam
- Cancer Molecular Pathology, School of Medicine & Dentistry, Griffith University, Gold Coast Campus, Southport, QLD, 4222, Australia; Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, 4222, Australia; Pathology Queensland, Gold Coast University Hospital, Southport, QLD, 4215, Australia
| | - Muhammad J A Shiddiky
- Rural Health Research Institute, Charles Sturt University, Orange, NSW, 2800, Australia.
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Pardini B, Ferrero G, Tarallo S, Gallo G, Francavilla A, Licheri N, Trompetto M, Clerico G, Senore C, Peyre S, Vymetalkova V, Vodickova L, Liska V, Vycital O, Levy M, Macinga P, Hucl T, Budinska E, Vodicka P, Cordero F, Naccarati A. A Fecal MicroRNA Signature by Small RNA Sequencing Accurately Distinguishes Colorectal Cancers: Results From a Multicenter Study. Gastroenterology 2023; 165:582-599.e8. [PMID: 37263306 DOI: 10.1053/j.gastro.2023.05.037] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 04/18/2023] [Accepted: 05/24/2023] [Indexed: 06/03/2023]
Abstract
BACKGROUND & AIMS Fecal tests currently used for colorectal cancer (CRC) screening show limited accuracy in detecting early tumors or precancerous lesions. In this respect, we comprehensively evaluated stool microRNA (miRNA) profiles as biomarkers for noninvasive CRC diagnosis. METHODS A total of 1273 small RNA sequencing experiments were performed in multiple biospecimens. In a cross-sectional study, miRNA profiles were investigated in fecal samples from an Italian and a Czech cohort (155 CRCs, 87 adenomas, 96 other intestinal diseases, 141 colonoscopy-negative controls). A predictive miRNA signature for cancer detection was defined by a machine learning strategy and tested in additional fecal samples from 141 CRC patients and 80 healthy volunteers. miRNA profiles were compared with those of 132 tumors/adenomas paired with adjacent mucosa, 210 plasma extracellular vesicle samples, and 185 fecal immunochemical test leftover samples. RESULTS Twenty-five miRNAs showed altered levels in the stool of CRC patients in both cohorts (adjusted P < .05). A 5-miRNA signature, including miR-149-3p, miR-607-5p, miR-1246, miR-4488, and miR-6777-5p, distinguished patients from control individuals (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.79-0.94) and was validated in an independent cohort (AUC, 0.96; 95% CI, 0.92-1.00). The signature classified control individuals from patients with low-/high-stage tumors and advanced adenomas (AUC, 0.82; 95% CI, 0.71-0.97). Tissue miRNA profiles mirrored those of stool samples, and fecal profiles of different gastrointestinal diseases highlighted miRNAs specifically dysregulated in CRC. miRNA profiles in fecal immunochemical test leftover samples showed good correlation with those of stool collected in preservative buffer, and their alterations could be detected in adenoma or CRC patients. CONCLUSIONS Our comprehensive fecal miRNome analysis identified a signature accurately discriminating cancer aimed at improving noninvasive diagnosis and screening strategies.
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Affiliation(s)
- Barbara Pardini
- Italian Institute for Genomic Medicine, Turin, Italy; Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy.
| | - Giulio Ferrero
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; Department of Computer Science, University of Turin, Turin, Italy
| | - Sonia Tarallo
- Italian Institute for Genomic Medicine, Turin, Italy; Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy
| | - Gaetano Gallo
- Department of Surgery, Sapienza University of Rome, Rome, Italy; Department of Colorectal Surgery, Clinica S. Rita, Vercelli, Italy
| | | | - Nicola Licheri
- Department of Computer Science, University of Turin, Turin, Italy
| | - Mario Trompetto
- Department of Colorectal Surgery, Clinica S. Rita, Vercelli, Italy
| | - Giuseppe Clerico
- Department of Colorectal Surgery, Clinica S. Rita, Vercelli, Italy
| | - Carlo Senore
- Epidemiology and Screening Unit-CPO, University Hospital Città della Salute e della Scienza, Turin, Italy
| | - Sergio Peyre
- LILT (Lega Italiana Lotta contro i Tumori), associazione provinciale di Biella, Biella, Italy
| | - Veronika Vymetalkova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic; Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - Ludmila Vodickova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic; Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - Vaclav Liska
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic; Department of Surgery, University Hospital and Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - Ondrej Vycital
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic; Department of Surgery, University Hospital and Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - Miroslav Levy
- Department of Surgery, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic
| | - Peter Macinga
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Tomas Hucl
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Eva Budinska
- RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic
| | - Pavel Vodicka
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic; Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | | | - Alessio Naccarati
- Italian Institute for Genomic Medicine, Turin, Italy; Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy.
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Mahdi Khanifar M, Zafari Z, Sheykhhasan M. Crosstalk between long non-coding RNAs and p53 signaling pathway in colorectal cancer: A review study. Pathol Res Pract 2023; 249:154756. [PMID: 37611430 DOI: 10.1016/j.prp.2023.154756] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 08/08/2023] [Accepted: 08/08/2023] [Indexed: 08/25/2023]
Abstract
Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and the third leading cause of cancer-related fatalities. Long non-coding RNAs (lncRNAs) are key regulators of diverse physiological processes and are dysregulated in a wide range of pathophysiological circumstances such as CRC. Studies revealed that aberrant expressions of lncRNAs clearly modulate the expression level of p53 gene in CRC, thereby transactivating multiple downstream pathways. P53 is regarded as a crucial tumor suppressor gene which promotes cell-cycle arrest, DNA repair, senescence or apoptosis in response to cellular stresses. P53 is also mutated in CRC as well as various types of human malignancies. Therefore, lncRNAs interact with the p53 signaling pathway in numerus ways and significantly influence CRC-related processes. The current findings in the investigation of the crosstalk between lncRNAs and the P53 pathway in controlling CRC carcinogenesis, tumor progression, and therapeutic resistance are summarized in the this review. A deeper knowledge of CRC carcinogenesis may also have implications in CRC prevention and treatment through more research.
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Affiliation(s)
- Mohammad Mahdi Khanifar
- School of Molecular Science, University of Western Australia, Perth, Western Australia, Australia; Department of Biology, Shahed University, Tehran, Iran
| | - Zahra Zafari
- Department of Biology, Shahed University, Tehran, Iran.
| | - Mohsen Sheykhhasan
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Department of Mesenchymal Stem Cells, Academic Center for Education, Culture and Research, Qom, Iran.
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Pecere S, Ciuffini C, Chiappetta MF, Petruzziello L, Papparella LG, Spada C, Gasbarrini A, Barbaro F. Increasing the accuracy of colorectal cancer screening. Expert Rev Anticancer Ther 2023; 23:583-591. [PMID: 37099725 DOI: 10.1080/14737140.2023.2207828] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/28/2023]
Abstract
INTRODUCTION Colorectal cancer (CRC) is a major health issue, being responsible for nearly 10% of all cancer-related deaths. Since CRC is often an asymptomatic or paucisymptomatic disease until it reaches advanced stages, screening is crucial for the diagnosis of preneoplastic lesions or early CRC. AREAS COVERED The aim of this review is to summarize the literature evidence on currently available CRC screening tools, with their pros and cons, focusing on the level of accuracy reached by each test over time. We also provide an overview of novel technologies and scientific advances that are currently being investigated and that in the future may represent real game-changers in the field of CRC screening. EXPERT OPINION We suggest that best screening modalities are annual or biennial FIT and colonoscopy every 10 years. We believe that the introduction of artificial intelligence (AI)-tools in the CRC screening field could lead to a significant improvement of the screening efficacy in reducing CRC incidence and mortality in the future. More resources should be put into implementing CRC programmes and support research project to further increase accuracy of CRC screening tests and strategies.
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Affiliation(s)
- Silvia Pecere
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Cristina Ciuffini
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Michele Francesco Chiappetta
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Lucio Petruzziello
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Luigi Giovanni Papparella
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Cristiano Spada
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Antonio Gasbarrini
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Federico Barbaro
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
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11
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Gautam SK, Khan P, Natarajan G, Atri P, Aithal A, Ganti AK, Batra SK, Nasser MW, Jain M. Mucins as Potential Biomarkers for Early Detection of Cancer. Cancers (Basel) 2023; 15:1640. [PMID: 36980526 PMCID: PMC10046558 DOI: 10.3390/cancers15061640] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 02/25/2023] [Accepted: 02/27/2023] [Indexed: 03/10/2023] Open
Abstract
Early detection significantly correlates with improved survival in cancer patients. So far, a limited number of biomarkers have been validated to diagnose cancers at an early stage. Considering the leading cancer types that contribute to more than 50% of deaths in the USA, we discuss the ongoing endeavors toward early detection of lung, breast, ovarian, colon, prostate, liver, and pancreatic cancers to highlight the significance of mucin glycoproteins in cancer diagnosis. As mucin deregulation is one of the earliest events in most epithelial malignancies following oncogenic transformation, these high-molecular-weight glycoproteins are considered potential candidates for biomarker development. The diagnostic potential of mucins is mainly attributed to their deregulated expression, altered glycosylation, splicing, and ability to induce autoantibodies. Secretory and shed mucins are commonly detected in patients' sera, body fluids, and tumor biopsies. For instance, CA125, also called MUC16, is one of the biomarkers implemented for the diagnosis of ovarian cancer and is currently being investigated for other malignancies. Similarly, MUC5AC, a secretory mucin, is a potential biomarker for pancreatic cancer. Moreover, anti-mucin autoantibodies and mucin-packaged exosomes have opened new avenues of biomarker development for early cancer diagnosis. In this review, we discuss the diagnostic potential of mucins in epithelial cancers and provide evidence and a rationale for developing a mucin-based biomarker panel for early cancer detection.
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Affiliation(s)
- Shailendra K. Gautam
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Parvez Khan
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Gopalakrishnan Natarajan
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Pranita Atri
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Abhijit Aithal
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Apar K. Ganti
- Fred & Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Division of Oncology-Hematology, Department of Internal Medicine, VA Nebraska Western Iowa Health Care System, University of Nebraska Medical Center, Omaha, NE 68105, USA
| | - Surinder K. Batra
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Fred & Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Mohd W. Nasser
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Fred & Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Maneesh Jain
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Fred & Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA
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12
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Chen YN, Shih CY, Guo SL, Liu CY, Shen MH, Chang SC, Ku WC, Huang CC, Huang CJ. Potential prognostic and predictive value of UBE2N, IMPDH1, DYNC1LI1 and HRASLS2 in colorectal cancer stool specimens. Biomed Rep 2023; 18:22. [PMID: 36846616 PMCID: PMC9945078 DOI: 10.3892/br.2023.1604] [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: 08/31/2022] [Accepted: 12/20/2022] [Indexed: 02/10/2023] Open
Abstract
Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide. The poor specificity and sensitivity of the fecal occult blood test has prompted the development of CRC-related genetic markers for CRC screening and treatment. Gene expression profiles in stool specimens are effective, sensitive and clinically applicable. Herein, a novel advantage of using cells shed from the colon is presented for cost-effective CRC screening. Molecular panels were generated through a series of leave-one-out cross-validation and discriminant analyses. A logistic regression model following reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry was used to validate a specific panel for CRC prediction. The panel, consisting of ubiquitin-conjugating enzyme E2 N (UBE2N), inosine monophosphate dehydrogenase 1 (IMPDH1), dynein cytoplasmic 1 light intermediate chain 1 (DYNC1LI1) and phospholipase A and acyltransferase 2 (HRASLS2), accurately recognized patients with CRC and could thus be further investigated as a potential prognostic and predictive biomarker for CRC. UBE2N, IMPDH1 and DYNC1LI1 expression levels were upregulated and HRASLS2 expression was downregulated in CRC tissues. The predictive power of the panel was 96.6% [95% confidence interval (CI), 88.1-99.6%] sensitivity and 89.7% (95% CI, 72.6-97.8%) specificity at a predicted cut-off value at 0.540, suggesting that this four-gene panel testing of stool specimens can faithfully mirror the state of the colon. On the whole, the present study demonstrates that screening for CRC or cancer detection in stool specimens collected non-invasively does not require the inclusion of an excessive number of genes, and colonic defects can be identified via the detection of an aberrant protein in the mucosa or submucosa.
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Affiliation(s)
- Yu-Nung Chen
- Division of Colorectal Surgery, Department of Surgery, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C
| | - Cheng-Yen Shih
- Division of Gastroenterology, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei 22174, Taiwan, R.O.C
| | - Shu-Lin Guo
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C.,Department of Anesthesiology, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C,Department of Anesthesiology, Tri-Service General Hospital and National Defense Medical Center, Taipei 11490, Taiwan, R.O.C
| | - Chih-Yi Liu
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C.,Division of Pathology, Sijhih Cathay General Hospital, New Taipei City 22174, Taiwan, R.O.C
| | - Ming-Hung Shen
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C.,Department of Surgery, Fu Jen Catholic University Hospital, New Taipei 24352, Taiwan, R.O.C.,PhD Program in Nutrition and Food Science, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C
| | - Shih-Chang Chang
- Division of Colorectal Surgery, Department of Surgery, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C
| | - Wei-Chi Ku
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C
| | - Chi-Cheng Huang
- Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan, R.O.C.,Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 10090, Taiwan, R.O.C.,Correspondence to: Dr Chi-Cheng Huang, Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Road, Taipei 11217, Taiwan, R.O.C.
| | - Chi-Jung Huang
- Department of Medical Research, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.,Department of Biochemistry, National Defense Medical Center, Taipei 11490, Taiwan, R.O.C.,Correspondence to: Dr Chi-Cheng Huang, Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Road, Taipei 11217, Taiwan, R.O.C.
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13
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Mirza S, Bhadresha K, Mughal MJ, McCabe M, Shahbazi R, Ruff P, Penny C. Liquid biopsy approaches and immunotherapy in colorectal cancer for precision medicine: Are we there yet? Front Oncol 2023; 12:1023565. [PMID: 36686736 PMCID: PMC9853908 DOI: 10.3389/fonc.2022.1023565] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 12/08/2022] [Indexed: 01/07/2023] Open
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally, with nearly half of patients detected in the advanced stages. This is due to the fact that symptoms associated with CRC often do not appear until the cancer has reached an advanced stage. This suggests that CRC is a cancer with a slow progression, making it curable and preventive if detected in its early stage. Therefore, there is an urgent clinical need to improve CRC early detection and personalize therapy for patients with this cancer. Recently, liquid biopsy as a non-invasive or nominally invasive approach has attracted considerable interest for its real-time disease monitoring capability through repeated sample analysis. Several studies in CRC have revealed the potential for liquid biopsy application in a real clinical setting using circulating RNA/miRNA, circulating tumor cells (CTCs), exosomes, etc. However, Liquid biopsy still remains a challenge since there are currently no promising results with high specificity and specificity that might be employed as optimal circulatory biomarkers. Therefore, in this review, we conferred the plausible role of less explored liquid biopsy components like mitochondrial DNA (mtDNA), organoid model of CTCs, and circulating cancer-associated fibroblasts (cCAFs); which may allow researchers to develop improved strategies to unravel unfulfilled clinical requirements in CRC patients. Moreover, we have also discussed immunotherapy approaches to improve the prognosis of MSI (Microsatellite Instability) CRC patients using neoantigens and immune cells in the tumor microenvironment (TME) as a liquid biopsy approach in detail.
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Affiliation(s)
- Sheefa Mirza
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,Department of Internal Medicine, Common Epithelial Cancer Research Centre, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Kinjal Bhadresha
- Hematology/Oncology Division, School of Medicine, Indiana University, Indianapolis, IN, United States
| | - Muhammed Jameel Mughal
- Department of Biochemistry and Molecular Medicine, School of Medicine and Health Science, The George Washington University, Washington, DC, United States
| | - Michelle McCabe
- Department of Anatomical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg, South Africa
| | - Reza Shahbazi
- Hematology/Oncology Division, School of Medicine, Indiana University, Indianapolis, IN, United States
| | - Paul Ruff
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,Department of Internal Medicine, Common Epithelial Cancer Research Centre, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Clement Penny
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,Department of Internal Medicine, Common Epithelial Cancer Research Centre, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,*Correspondence: Clement Penny,
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14
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Olejárová S, Moravčík R, Herichová I. 2.4 GHz Electromagnetic Field Influences the Response of the Circadian Oscillator in the Colorectal Cancer Cell Line DLD1 to miR-34a-Mediated Regulation. Int J Mol Sci 2022; 23:13210. [PMID: 36361993 PMCID: PMC9656412 DOI: 10.3390/ijms232113210] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 10/26/2022] [Accepted: 10/27/2022] [Indexed: 10/15/2023] Open
Abstract
Radiofrequency electromagnetic fields (RF-EMF) exert pleiotropic effects on biological processes including circadian rhythms. miR-34a is a small non-coding RNA whose expression is modulated by RF-EMF and has the capacity to regulate clock gene expression. However, interference between RF-EMF and miR-34a-mediated regulation of the circadian oscillator has not yet been elucidated. Therefore, the present study was designed to reveal if 24 h exposure to 2.4 GHz RF-EMF influences miR-34a-induced changes in clock gene expression, migration and proliferation in colorectal cancer cell line DLD1. The effect of up- or downregulation of miR-34a on DLD1 cells was evaluated using real-time PCR, the scratch assay test and the MTS test. Administration of miR-34a decreased the expression of per2, bmal1, sirtuin1 and survivin and inhibited proliferation and migration of DLD1 cells. When miR-34a-transfected DLD1 cells were exposed to 2.4 GHz RF-EMF, an increase in cry1 mRNA expression was observed. The inhibitory effect of miR-34a on per2 and survivin was weakened and abolished, respectively. The effect of miR-34a on proliferation and migration was eliminated by RF-EMF exposure. In conclusion, RF-EMF strongly influenced regulation mediated by the tumour suppressor miR-34a on the peripheral circadian oscillator in DLD1 cells.
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Affiliation(s)
| | | | - Iveta Herichová
- Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University Bratislava, 842 15 Bratislava, Slovakia
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15
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Expression profiling of cancer-related long non-coding RNAs revealed upregulation and biomarker potential of HAR1B and JPX in colorectal cancer. Mol Biol Rep 2022; 49:6075-6084. [DOI: 10.1007/s11033-022-07396-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 03/14/2022] [Accepted: 03/16/2022] [Indexed: 10/18/2022]
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16
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Liu J, Shang G. The Roles of Noncoding RNAs in the Development of Osteosarcoma Stem Cells and Potential Therapeutic Targets. Front Cell Dev Biol 2022; 10:773038. [PMID: 35252166 PMCID: PMC8888953 DOI: 10.3389/fcell.2022.773038] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 01/31/2022] [Indexed: 12/11/2022] Open
Abstract
Osteosarcoma (OS) is the common bone tumor in children and adolescents. Because of chemotherapy resistance, the OS patients have a poor prognosis. The one reason of chemotherapeutic resistance is the development of cancer stem cells (CSCs). CSCs represent a small portion of tumor cells with the capacity of self-renewal and multipotency, which are associated with tumor initiation, metastasis, recurrence and drug resistance. Recently, noncoding RNAs (ncRNAs) have been reported to critically regulate CSCs. Therefore, in this review article, we described the role of ncRNAs, especially miRNAs, lncRNAs and circRNAs, in regulating CSCs development and potential mechanisms. Specifically, we discussed the role of multiple miRNAs in targeting CSCs, including miR-26a, miR-29b, miR-34a, miR-133a, miR-143, miR-335, miR-382, miR-499a, miR-1247, and let-7days. Moreover, we highlighted the functions of lncRNAs in regulating CSCs in OS, such as B4GALT1-AS1, DANCR, DLX6-AS1, FER1L4, HIF2PUT, LINK-A, MALAT1, SOX2-OT, and THOR. Due to the critical roles of ncRNAs in regulation of OS CSCs, targeting ncRNAs might be a novel strategy for eliminating CSCs for OS therapy.
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Affiliation(s)
- Jinxin Liu
- Department of Orthopedic Surgery, Shengjing Hospital, China Medical University, Shenyang, China
| | - Guanning Shang
- Department of Orthopedic Surgery, Shengjing Hospital, China Medical University, Shenyang, China
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17
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Song D, Zhang Q, Zhang H, Zhan L, Sun X. MiR-130b-3p promotes colorectal cancer progression by targeting CHD9. Cell Cycle 2022; 21:585-601. [PMID: 35100082 PMCID: PMC8942501 DOI: 10.1080/15384101.2022.2029240] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. Previous research revealed that microRNA 130b-3p (miR-130b-3p) significantly upregulated in CRC patients can be detected in feces from patients with such a neoplasm. In this study, the biological role and molecular mechanism of miR-130b-3p in CRC were explored. The miR-130b-3p level in CRC tissues, feces and cell lines was measured using RT-qPCR analysis. CCK-8, EdU, TUNEL, flow cytometry, Western blotting, and in vivo experiments were performed to explore the biological function of miR-130b-3p in CRC progression. For this purpose, 16 BALB/c nude mice were assigned to two groups. The experiment lasted for four months. Bioinformatics analysis and luciferase reporter assay were used to investigate the regulatory mechanism related to miR-130b-3p. In our research, miR-130b-3p was upregulated in CRC tissues and cells and it was detected in feces from CRC patients. Moreover, miR-130b-3p inhibition suppressed CRC cell proliferation and promoted cell apoptosis in vitro as well as repressed CRC tumor growth in vivo. Mechanistically, miR-130b-3p directly targeted the 3'untranslated region (UTR) of chromodomain helicase DNA binding protein 9 (CHD9) and negatively regulated CHD9 expression. Furthermore, CHD9 played an anti-oncogenic role in CRC. Inhibition of CHD9 expression was likely to be a key mechanism by which miR-130b-3p increased CRC cell growth, with a target protector experiment revealing miR-130b-3p influenced proliferation via direct inhibition of CHD9. MiR-130b-3p promotes the progression and tumorigenesis of CRC at least partially by targeting CHD9.Abbreviations: CRC: Colorectal cancer; miR-130b-3p: microRNA 130b-3p; CHD9: chromodomain helicase DNA binding protein 9; UTR: untranslated region; FIT: fecal immunochemical test; AAs: advanced adenomas.
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Affiliation(s)
- Dan Song
- Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, Jiangsu, China,Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China,Dan Song Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, Jiangsu, China
| | - Qian Zhang
- Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, Jiangsu, China
| | - Hao Zhang
- Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, Jiangsu, China
| | - Liangliang Zhan
- Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, Jiangsu, China
| | - Xinchen Sun
- Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China,CONTACT Xinchen Sun Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, China
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18
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Moosavy SH, Koochakkhani S, Barazesh M, Mohammadi S, Ahmadi K, Inchehsablagh BR, Kavousipour S, Eftekhar E, Mokaram P. In silico Analysis of Single Nucleotide Polymorphisms Associated with MicroRNA
Regulating 5-fluorouracil Resistance in Colorectal Cancer. LETT DRUG DES DISCOV 2022. [DOI: 10.2174/1570180818666210930161618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
Due to the broad influence and reversible nature of microRNA (miRNA) on the
expression and regulation of target genes, researchers suggest that miRNAs and single nucleotide polymorphisms
(SNPs) in miRNA genes interfere with 5-fluorouracil (5-FU) drug resistance in colorectal
cancer chemotherapy.
Methods:
Computational assessment and cataloging of miRNA gene polymorphisms that target mRNA
transcripts directly or indirectly through regulation of 5-FU chemoresistance in CRC were screened out
by applying various universally accessible datasets such as miRNA SNP3.0 software.
Results:
1255 SNPs in 85 miRNAs affecting 5-FU resistance (retrieved from literature) were detected.
Computational analysis showed that 167 from 1255 SNPs alter microRNA expression levels leading to
inadequate response to 5-FU resistance in CRC. Among these 167 SNPs, 39 were located in the seed
region of 25/85 miRNA and were more critical than other SNPs. Has-miR-320a-5p with 4 SNP in seed
region was miRNA with the most number of SNPs. On the other hand, it has been identified that proteoglycan
in cancer, adherents junction, ECM-receptor interaction, Hippo signaling pathway, TGF-beta signaling
cascade, biosynthesis of fatty acid, and fatty acid metabolism were the most important pathways
targeted by these 85 predicted miRNAs.
Conclusion:
Our data suggest 39 SNPs in the seed region of 25 miRNAs as catalog in miRNA genes that
control the 5-FU resistance in CRC. These data also identify the most important pathways regulated by
miRNA.
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Affiliation(s)
- Seyed Hamid Moosavy
- Endocrinology and Metabolism Research Center, Hormozgan University of Medical Science, Bandar Abbas, Iran
| | - Shabnaz Koochakkhani
- Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar
Abbas 7919915519, Iran
| | - Mahdi Barazesh
- School of Paramedical Sciences, Gerash University of Medical Sciences, Gerash, Iran
| | - Shiva Mohammadi
- Department of Medical Biotechnology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad,
Iran
| | - Khadijeh Ahmadi
- Infection and Tropical Disease Research Center, Hormozgan Health Institute, Hormozgan University of Medical
Science, Bandar Abbas, Iran
| | - Behnaz Rahnama Inchehsablagh
- Department of Physiology and Student Research Committee, Hormozgan University of
Medical Sciences, Bandar Abbas, Iran
| | - Soudabeh Kavousipour
- Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar
Abbas 7919915519, Iran
| | - Ebrahim Eftekhar
- Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar
Abbas 7919915519, Iran
| | - Pooneh Mokaram
- Autophagy Research Center, Shiraz University of Medical Sciences, Iran
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19
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Novel Diagnostic Biomarkers in Colorectal Cancer. Int J Mol Sci 2022; 23:ijms23020852. [PMID: 35055034 PMCID: PMC8776048 DOI: 10.3390/ijms23020852] [Citation(s) in RCA: 125] [Impact Index Per Article: 41.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 12/27/2021] [Accepted: 01/03/2022] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is still a leading cause of cancer death worldwide. Less than half of cases are diagnosed when the cancer is locally advanced. CRC is a heterogenous disease associated with a number of genetic or somatic mutations. Diagnostic markers are used for risk stratification and early detection, which might prolong overall survival. Nowadays, the widespread use of semi-invasive endoscopic methods and feacal blood tests characterised by suboptimal accuracy of diagnostic results has led to the detection of cases at later stages. New molecular noninvasive tests based on the detection of CRC alterations seem to be more sensitive and specific then the current methods. Therefore, research aiming at identifying molecular markers, such as DNA, RNA and proteins, would improve survival rates and contribute to the development of personalized medicine. The identification of “ideal” diagnostic biomarkers, having high sensitivity and specificity, being safe, cheap and easy to measure, remains a challenge. The purpose of this review is to discuss recent advances in novel diagnostic biomarkers for tumor tissue, blood and stool samples in CRC patients.
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20
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Sadri S, Rejali L, Hadizadeh M, Aghdaei HA, Young C, Nazemalhosseini-Mojarad E, Zali MR, Bonab MA. ANRIL as a prognostic biomarker in colon pre-cancerous lesion detection via non-invasive sampling. Genes Genet Syst 2021; 96:285-292. [DOI: 10.1266/ggs.21-00102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Affiliation(s)
- Shadi Sadri
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shaheed Beheshti University of Medical Sciences
| | - Leili Rejali
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shaheed Beheshti University of Medical Sciences
| | | | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shaheed Beheshti University of Medical Sciences
| | - Chris Young
- Leicester School of Allied Health Sciences, Faculty of Health and Life Sciences, De Montfort University
| | - Ehsan Nazemalhosseini-Mojarad
- Gastroenterology and Liver Diseases Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shaheed Beheshti University of Medical Sciences
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shaheed Beheshti University of Medical Sciences
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21
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He S, Zhou C, Peng H, Lin M. Recent advances in fecal gene detection for colorectal cancer diagnosis. Biomark Med 2021; 15:1299-1308. [PMID: 34544268 DOI: 10.2217/bmm-2021-0269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
There has been a gradual increase in the incidence of colorectal cancer (CRC) in recent years. Most patients lack obvious early symptoms, but are commonly in mid and advanced stages when the symptoms become evident, with rather high mortalities. Early diagnosis, treatment and recurrence monitoring are crucial to improving the recovery rate of CRC. Studies have shown that tumor-related genes can be detected in the feces of CRC patients. Owing to non-invasiveness, convenient sampling and continuous dynamic monitoring, fecal gene detection may be applicable to CRC screening, diagnosis, prognostic assessment and recurrence monitoring. Herein, we review the research advances in fecal gene detection for CRC diagnosis.
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Affiliation(s)
- Siyu He
- Clinical Laboratory, Taizhou People's Hospital (Postgraduate training base of Dalian Medical University), Taizhou, 225300, Jiangsu, China
| | - Chenglin Zhou
- Clinical Laboratory, Taizhou People's Hospital (Postgraduate training base of Dalian Medical University), Taizhou, 225300, Jiangsu, China
| | - Hailin Peng
- Clinical Laboratory, Taizhou People's Hospital (Postgraduate training base of Dalian Medical University), Taizhou, 225300, Jiangsu, China
| | - Mei Lin
- Clinical Laboratory, Taizhou People's Hospital (Postgraduate training base of Dalian Medical University), Taizhou, 225300, Jiangsu, China
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22
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Zhao L, Xiong M, Liu Y. Baicalin enhances the proliferation and invasion of trophoblasts and suppresses vascular endothelial damage by modulating long non-coding RNA NEAT1/miRNA-205-5p in hypertensive disorder complicating pregnancy. J Obstet Gynaecol Res 2021; 47:3060-3070. [PMID: 34101306 DOI: 10.1111/jog.14789] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 03/08/2021] [Accepted: 03/22/2021] [Indexed: 12/31/2022]
Abstract
AIM Trophoblastic and vascular endothelial injuries were closely associated with the pathogenesis of hypertensive disorder complicating pregnancy (HDCP). The present study was designed to determine the functional role of baicalin in the proliferation and invasion of trophoblasts and vascular endothelial injury. METHODS Ang II was adopted to stimulate HTR-8/SVneo and human umbilical vein endothelial cells (HUVECs). Cell viability was examined by CCK-8 assay. Flow cytometry and TUNEL staining determined cell apoptosis. Invasive ability of HTR-8/SVneo cells was measured by transwell assay. In vitro angiogenesis of HUVECs was assessed by Tube formation assay. In addition, the production of reactive oxygen species (ROS) was determined by DCFH-DA staining. Furthermore, long non-coding RNA (lncRNA) NEAT1 and miRNA-205-5p levels were detected using real-time quantitative polymerase chain reaction and the binding relationship between lncRNA NEAT1 and miRNA-205-5p was verified by dual-luciferase reporter assay. Moreover, interactions among lncRNA NEAT1, miRNA-205-5p, and MMP9 or vascular endothelial growth factor (VEGF) were confirmed by RNA immunoprecipitation assay. RESULTS Baicalin visibly improved cell viability, reduced the apoptosis of Ang II-stimulated HTR-8/SVneo and HUVEC cells, and repressed overproduction of ROS. Additionally, baicalin promoted the invasion of Ang II-stimulated HTR-8/SVneo cells and induced a stronger in vitro angiogenesis of Ang II-stimulated HUVECs. What's more, baicalin upregulated lncRNA NEAT1 expression and downregulated miR-205-5p expression. LncRNA NEAT1 sponged miR-205-5p and inhibited the combination of miR-205-5p and MMP9 or VEGF. CONCLUSIONS Baicalin can facilitate the proliferation and invasion of trophoblasts and alleviate vascular endothelial damage by upregulating lncRNA NEAT1 to impede the interaction between miR-205-5p and MMP9 or VEGF.
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Affiliation(s)
- Lidong Zhao
- Department of Emergency Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai, China
| | - Miao Xiong
- Department of Obstetrics, Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai, China
| | - Yang Liu
- Department of Obstetrics, Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai, China
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Novák J, Macháčková T, Krejčí J, Bienertová-Vašků J, Slabý O. MicroRNAs as theranostic markers in cardiac allograft transplantation: from murine models to clinical practice. Theranostics 2021; 11:6058-6073. [PMID: 33897899 PMCID: PMC8058726 DOI: 10.7150/thno.56327] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 03/21/2021] [Indexed: 12/11/2022] Open
Abstract
Congestive heart failure affects about 23 million people worldwide, and cardiac allograft transplantation remains one of the last options for patients with terminal refractory heart failure. Besides the infectious or oncological complications, the prognosis of patients after heart transplantation is affected by acute cellular or antibody-mediated rejection and allograft vasculopathy development. Current monitoring of both conditions requires the performance of invasive procedures (endomyocardial biopsy sampling and coronary angiography or optical coherence tomography, respectively) that are costly, time-demanding, and non-comfortable for the patient. Within this narrative review, we focus on the potential pathophysiological and clinical roles of microRNAs (miRNAs, miRs) in the field of cardiac allograft transplantation. Firstly, we provide a general introduction about the status of cardiac allograft function monitoring and the discovery of miRNAs as post-transcriptional regulators of gene expression and clinically relevant biomarkers found in the extracellular fluid. After this general introduction, information from animal and human studies are summarized to underline the importance of miRNAs both in the pathophysiology of the rejection process, the possibility of its modulation by altering miRNAs levels, and last but not least, about the use of miRNAs in the clinical practice to diagnose or predict the rejection occurrence.
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Affiliation(s)
- Jan Novák
- Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5-A18, 625 00, Brno, Czech Republic
- Second Department of Internal Medicine, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Pekařská 53, 65691, Brno, Czech Republic
- Central European Institute of Technology, Masaryk University, Kamenice 5-A35, 625 00, Brno, Czech Republic
| | - Táňa Macháčková
- Central European Institute of Technology, Masaryk University, Kamenice 5-A35, 625 00, Brno, Czech Republic
| | - Jan Krejčí
- Department of Cardiovascular Diseases, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Pekařská 53, 65691, Brno, Czech Republic
| | - Julie Bienertová-Vašků
- Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5-A18, 625 00, Brno, Czech Republic
- RECETOX, Faculty of Sciences, Masaryk University, Kamenice 5-A29, 625 00, Brno, Czech Republic
| | - Ondřej Slabý
- Central European Institute of Technology, Masaryk University, Kamenice 5-A35, 625 00, Brno, Czech Republic
- Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic
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lncRNA SNHG4 modulates colorectal cancer cell cycle and cell proliferation through regulating miR-590-3p/CDK1 axis. Aging (Albany NY) 2021; 13:9838-9858. [PMID: 33744866 PMCID: PMC8064176 DOI: 10.18632/aging.202737] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 02/08/2021] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) is a prevalent malignancy worldwide. The development of genome sequencing technology has allowed the discovery that epigenetic regulation might play a critical role in CRC tumorigenesis. In the present study, we found that the long noncoding RNA (lncRNA) SNHG4 was dramatically increased in CRC tissue samples and cell lines based on both publicly available and experimental data. SNHG4 knockdown suppressed the viability and colony formation capacity of CRC cells. The expression of CDK1 was considerably increased in CRC tissue samples and cells and had a positive correlation with the expression of SNHG4 in CRC. SNHG4 silencing not only caused S phase cell cycle arrest but also significantly downregulated the CDK1, cyclin B1, and cyclin A2 protein levels in CRC cells. miR-590-3p simultaneously bound to SNHG4 and CDK1. miR-590-3p functioned to inhibit CDK1 expression. miR-590-3p overexpression exerted the same effects on the CRC cell phenotype as SNHG4 knockdown. The effects of si-SNHG4 on CRC cells were significantly reversed by anti-miR-590-3p, indicating that SNHG4 relieved the miR-590-3p-induced inhibition of CDK1 by acting as a competing endogenous RNA (ceRNA). In vivo, SNHG4 silencing inhibited subcutaneously transplanted tumor growth and decreased cell cycle marker levels, whereas miR-590-3p inhibition exerted the opposite effects. The in vivo effects of SNHG4 silencing were also reversed by miR-590-3p inhibition. The SNHG4/miR-590-3p/CDK1 axis influences the cell cycle to modulate CRC cell proliferation and subcutaneously transplanted tumor growth. Further application of this axis still requires analysis using more animal models and clinical investigations.
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25
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Francavilla A, Turoczi S, Tarallo S, Vodicka P, Pardini B, Naccarati A. Exosomal microRNAs and other non-coding RNAs as colorectal cancer biomarkers: a review. Mutagenesis 2021; 35:243-260. [PMID: 31784760 DOI: 10.1093/mutage/gez038] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 10/14/2019] [Indexed: 12/12/2022] Open
Abstract
The circulating human transcriptome, which includes both coding and non-coding RNA (ncRNA) molecules, represents a rich source of potential biomarkers for colorectal cancer (CRC) that has only recently been explored. In particular, the release of RNA-containing extracellular vesicles (EVs), in a multitude of different in vitro cell systems and in a variety of body fluids, has attracted wide interest. The role of RNA species in EVs is still not fully understood, but their capacity to act as a form of distant communication between cells and their higher abundance in association with cancer demonstrated their relevance. In this review, we report the evidence from both in vitro and human studies on microRNAs (miRNAs) and other ncRNA profiles analysed in EVs in relation to CRC as diagnostic, prognostic and predictive markers. The studies so far highlighted that, in exosomes, the most studied category of EVs, several miRNAs are able to accurately discriminate CRC cases from controls as well as to describe the progression of the disease and its prognosis. Most of the time, the in vitro findings support the miRNA profiles detected in human exosomes. The expression profiles measured in exosomes and other EVs differ and, interestingly, there is a variability of expression also among different subsets of exosomes according to their proteic profile. On the other hand, evidence is still limited for what concerns exosome miRNAs as early diagnostic and predictive markers of treatment. Several other ncRNAs that are carried by exosomes, mostly long ncRNAs and circular RNAs, seem also to be dysregulated in CRC. Besides various technical challenges, such as the standardisation of EVs isolation methods and the optimisation of methodologies to characterise the whole spectrum of RNA molecules in exosomes, further studies are needed in order to elucidate their relevance as CRC markers.
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Affiliation(s)
- Antonio Francavilla
- Italian Institute for Genomic Medicine (IIGM), c/o IRCCS Candiolo, Candiolo, Turin, Italy
| | - Szimonetta Turoczi
- Italian Institute for Genomic Medicine (IIGM), c/o IRCCS Candiolo, Candiolo, Turin, Italy
| | - Sonia Tarallo
- Italian Institute for Genomic Medicine (IIGM), c/o IRCCS Candiolo, Candiolo, Turin, Italy
| | - Pavel Vodicka
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Prague, Czech Republic
| | - Barbara Pardini
- Italian Institute for Genomic Medicine (IIGM), c/o IRCCS Candiolo, Candiolo, Turin, Italy
| | - Alessio Naccarati
- Italian Institute for Genomic Medicine (IIGM), c/o IRCCS Candiolo, Candiolo, Turin, Italy.,Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Prague, Czech Republic
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26
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Supplitt S, Karpinski P, Sasiadek M, Laczmanska I. Current Achievements and Applications of Transcriptomics in Personalized Cancer Medicine. Int J Mol Sci 2021; 22:1422. [PMID: 33572595 PMCID: PMC7866970 DOI: 10.3390/ijms22031422] [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: 11/20/2020] [Revised: 01/19/2021] [Accepted: 01/21/2021] [Indexed: 12/12/2022] Open
Abstract
Over the last decades, transcriptome profiling emerged as one of the most powerful approaches in oncology, providing prognostic and predictive utility for cancer management. The development of novel technologies, such as revolutionary next-generation sequencing, enables the identification of cancer biomarkers, gene signatures, and their aberrant expression affecting oncogenesis, as well as the discovery of molecular targets for anticancer therapies. Transcriptomics contribute to a change in the holistic understanding of cancer, from histopathological and organic to molecular classifications, opening a more personalized perspective for tumor diagnostics and therapy. The further advancement on transcriptome profiling may allow standardization and cost reduction of its analysis, which will be the next step for transcriptomics to become a canon of contemporary cancer medicine.
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Affiliation(s)
- Stanislaw Supplitt
- Department of Genetics, Wroclaw Medical University, Marcinkowskiego 1, 50-368 Wroclaw, Poland; (P.K.); (M.S.); (I.L.)
| | - Pawel Karpinski
- Department of Genetics, Wroclaw Medical University, Marcinkowskiego 1, 50-368 Wroclaw, Poland; (P.K.); (M.S.); (I.L.)
- Laboratory of Genomics and Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland
| | - Maria Sasiadek
- Department of Genetics, Wroclaw Medical University, Marcinkowskiego 1, 50-368 Wroclaw, Poland; (P.K.); (M.S.); (I.L.)
| | - Izabela Laczmanska
- Department of Genetics, Wroclaw Medical University, Marcinkowskiego 1, 50-368 Wroclaw, Poland; (P.K.); (M.S.); (I.L.)
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27
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Liu Y, Zhang B, Cao WB, Wang HY, Niu L, Zhang GZ. Study on Clinical Significance of LncRNA EGOT Expression in Colon Cancer and Its Effect on Autophagy of Colon Cancer Cells. Cancer Manag Res 2020; 12:13501-13512. [PMID: 33408522 PMCID: PMC7781029 DOI: 10.2147/cmar.s285254] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Accepted: 11/16/2020] [Indexed: 12/16/2022] Open
Abstract
Background Colon cancer (CC) is a common digestive tract tumor, and the increase of new and dead patients every year still puzzles clinical workers. LncRNA eosinophil granule ontogeny transcript (EGOT), as a newly discovered long-chain noncoding RNA (lncRNA), is differentially expressed in other tumors, but there are fewer studies of it in colon cancer. Methods The relative expression and diagnostic value of EGOT in CC were detected and analyzed by starBase online website and qRT-PCR. The patients were followed-up for five years, and Cox regression was used to analyze the independent prognostic factors of CC. The effects of EGOT overexpression (pcDNA-RGOT) on CC cell function were detected by CCK-8, transwell and flow cytometry. WB was applied to detect autophagy. The influence of knocking out EGOT (sh-EGOT) on tumor growth was observed by tumor allogeneic inhibition. The microRNA (miR) and mRNA in the downstream of EGOT were predicted and the ceRNA network map was drawn. Results The online database and qRT-PCR detection showed that EGOT was highly expression in patients with CC and had good diagnostic value. The five-year survival rate of patients with high expression of EGOT decreased. EGOT and TNM staging were independent prognostic factors of patients with CC. Functional analysis revealed that the growth and invasion abilities of cells increased, and the apoptosis rate decreased after overexpression. Upregulation of EGOT inhibited autophagy of CC cells and promoted cell growth. However, the tumor in nude mice was significantly lessened after knockout of EGOT. Bioinformatic analysis showed that microRNA-33a-5p and microRNA-33b-5p had targeted binding sites with EGOT. Conclusion EGOT is highly expressed in CC and has high diagnostic value. In addition, inhibition of EGOT can promote autophagy of CC cells and inhibit cell growth and metastasis, which is expected to be a potential therapeutic index.
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Affiliation(s)
- Yang Liu
- Department of General Surgery, North China University of Science and Technology Affiliated Hospital, Tangshan City, Hebei Province 063000, People's Republic of China
| | - Bo Zhang
- Department of General Surgery, North China University of Science and Technology Affiliated Hospital, Tangshan City, Hebei Province 063000, People's Republic of China
| | - Wen-Bin Cao
- Department of General Surgery, North China University of Science and Technology Affiliated Hospital, Tangshan City, Hebei Province 063000, People's Republic of China
| | - Hai-Yan Wang
- Department of Oncology, The 982 Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Tangshan City, Hebei Province 063000, People's Republic of China
| | - Lei Niu
- Department of Respiratory Medicine, Tangshan Hong Ci Hospital Co. Ltd, Tangshan City, Hebei Province 063000, People's Republic of China
| | - Guo-Zhi Zhang
- Department of General Surgery, North China University of Science and Technology Affiliated Hospital, Tangshan City, Hebei Province 063000, People's Republic of China
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28
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Liu Y, Li Q, Tang D, Li M, Zhao P, Yang W, Shu L, Wang J, He Z, Li Y, Wang F. SNHG17 promotes the proliferation and migration of colorectal adenocarcinoma cells by modulating CXCL12-mediated angiogenesis. Cancer Cell Int 2020; 20:566. [PMID: 33292246 PMCID: PMC7690009 DOI: 10.1186/s12935-020-01621-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023] Open
Abstract
Background Colorectal adenocarcinoma (CRA) is one of the leading causes of cancer-related deaths in the world. Long non-coding RNAs (lncRNAs) have been implicated to be effective regulators in the disease course of human cancers, including CRA. Small nucleolar RNA host gene 17 (SNHG17) belongs to lncRNAs, and it has been reported in breast cancer and gastric cancer. However, the function of SNHG17 and its mechanism in CRA progression remain largely unknown. In this study, we attended to shedding some light on the role of SNHG17 in CRA. Methods RT-qPCR was used to assess SNHG17 expression in CRA cells. CCK-8 assay, colony formation and transwell assay were carried out to detect the regulatory effect of SNHG17 silencing on CRA cell proliferation and migration. The angiogenesis of SNHG7-downregulated CRA cells was analyzed by tube formation assay. Mechanism experiments were conducted to identify the interaction between miR-23a-3p and SNHG17 or C-X-C motif chemokine ligand 12 (CXCL12). Results SNHG17 possessed with high expression in CRA cells. Knockdown of SNHG17 caused the inhibition on CRA cell proliferation and migration. SNHG17 promoted CRA cell proliferation and migration by sponging miR-23a-3p to upregulate CXCL12. Conclusion SNHG17 promotes the proliferation and migration of CRA cells by inhibiting miR-23a-3p to modulate CXCL12-mediated angiogenesis.
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Affiliation(s)
- Yang Liu
- Department of Science and Education, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. 71 Bao Shan North Road, Yunyan District, Guiyang, 550001, Guizhou, China. .,National & Guizhou Joint Engineering Laboratory for Cell Engineering and Biomedicine Technique, Guizhou Medical University, Guiyang, 550004, Guizhou, China.
| | - Qinshan Li
- National & Guizhou Joint Engineering Laboratory for Cell Engineering and Biomedicine Technique, Guizhou Medical University, Guiyang, 550004, Guizhou, China
| | - Dongxin Tang
- Department of Science and Education, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. 71 Bao Shan North Road, Yunyan District, Guiyang, 550001, Guizhou, China
| | - Mengxing Li
- Department of Hematology, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550004, Guizhou, China
| | - Peng Zhao
- Department of Hematology, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550004, Guizhou, China
| | - Wenxiu Yang
- Department of Hematology, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550004, Guizhou, China
| | - Liping Shu
- National & Guizhou Joint Engineering Laboratory for Cell Engineering and Biomedicine Technique, Guizhou Medical University, Guiyang, 550004, Guizhou, China
| | - Jishi Wang
- Department of Hematology, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550004, Guizhou, China
| | - Zhixu He
- National & Guizhou Joint Engineering Laboratory for Cell Engineering and Biomedicine Technique, Guizhou Medical University, Guiyang, 550004, Guizhou, China.,Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, 563006, Guizhou, China
| | - Yanju Li
- Department of Hematology, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang, 550004, Guizhou, China.
| | - Feiqing Wang
- Department of Science and Education, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. 71 Bao Shan North Road, Yunyan District, Guiyang, 550001, Guizhou, China.
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Poursheikhani A, Abbaszadegan MR, Kerachian MA. Mechanisms of long non-coding RNA function in colorectal cancer tumorigenesis. Asia Pac J Clin Oncol 2020; 17:7-23. [PMID: 32970938 DOI: 10.1111/ajco.13452] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 08/03/2020] [Indexed: 12/14/2022]
Abstract
Colorectal cancer (CRC) is one of the most common cancers globally. Although a variety of CRC screening methods have been developed, many patients are diagnosed at advanced stages of CRC with tumor invasion and distance metastasis. Several studies have suggested the long noncoding RNAs (lncRNAs) as one of the main contributors in CRC tumorigenesis, although the exact underlying mechanism of lncRNAs in CRC is still unknown. Numerous studies have indicated aberrant expression of lncRNAs in CRC through different modes of action such as cell proliferation, apoptosis, cell cycle, DNA repair response, drug-resistance, migration, and metastasis. Furthermore, lncRNA polymorphisms can influence the risk of CRC development. Accordingly, lncRNAs can be served as promising diagnostic or prognostic biomarkers and also desired therapeutic targets affecting the outcome of patients with CRC. In this review, we summarized the updated and novel evidence that identifies different roles of lncRNAs in the tumorigenesis of CRC.
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Affiliation(s)
- Arash Poursheikhani
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Reza Abbaszadegan
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Amin Kerachian
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Cancer Genetics Research Unit, Reza Radiotherapy, and Oncology Center, Mashhad, Iran
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Huang L, Liang XZ, Deng Y, Liang YB, Zhu X, Liang XY, Luo DZ, Chen G, Fang YY, Lan HH, Zeng JH. Prognostic value of small nucleolar RNAs (snoRNAs) for colon adenocarcinoma based on RNA sequencing data. Pathol Res Pract 2020; 216:152937. [PMID: 32312483 DOI: 10.1016/j.prp.2020.152937] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Revised: 02/29/2020] [Accepted: 03/21/2020] [Indexed: 01/17/2023]
Abstract
Although the molecular studies of single gastrointestinal tumors have been widely reported by media, it is not clear about the function of small nucleolar RNA (snoRNA) in the progression, development and prognostic significance in colon adenocarcinoma, and its certain molecular mechanisms and functions remain to be studied. This study aims to dig out the gene expression data profile of colon adenocarcinoma and construct the prognostic molecular pathology prediction-evaluation, ultimately revealing the clinical prognostic value of snoRNA in colon adenocarcinoma. 932 differentially expressed snoRNAs of the colon adenocarcinoma were obtained by edgeR R package. Only 4 prognostically-significant snoRNAs (SNORD14E, SNORD67, SNORD12C, and SNORD17) (P < 0.05) were discovered after univariate COX regression mode analysis. Moreover, through multivariate COX regression mode analysis, 2 prognostically-significant snoRNAs (SNORD14E and SNORD67) (P < 0.05) were obtained. Using the above 473 COAD samples, a prognostic model of risk score was constructed. The inflection point of the prognostic risk score acted as a boundary to divide the patients into high-risk and low-risk groups. The K-M survival curve of the prognostic model of risk score revealed that high risk group has a lower survival rate (P < 0.05). The research has successfully provided valuable prognostic factors and prognostic models for patients with malignant colon tumor.
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Affiliation(s)
- Li Huang
- Department of Clinical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/Nanning Second People's Hospital, Nanning, Guangxi Zhuang Autonomous Region, PR China
| | - Xu-Zhi Liang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, PR China
| | - Yun Deng
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, PR China
| | - Yong-Biao Liang
- Department of Clinical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/Nanning Second People's Hospital, Nanning, Guangxi Zhuang Autonomous Region, PR China
| | - Xu Zhu
- Department of Clinical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/Nanning Second People's Hospital, Nanning, Guangxi Zhuang Autonomous Region, PR China
| | - Xiu-Yun Liang
- Department of Clinical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/Nanning Second People's Hospital, Nanning, Guangxi Zhuang Autonomous Region, PR China
| | - Dian-Zhong Luo
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, PR China
| | - Gang Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, PR China
| | - Ye-Ying Fang
- Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, PR China
| | - Hui-Hua Lan
- Department of Clinical Laboratory, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region, PR China.
| | - Jiang-Hui Zeng
- Department of Clinical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/Nanning Second People's Hospital, Nanning, Guangxi Zhuang Autonomous Region, PR China.
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Loktionov A. Biomarkers for detecting colorectal cancer non-invasively: DNA, RNA or proteins? World J Gastrointest Oncol 2020; 12:124-148. [PMID: 32104546 PMCID: PMC7031146 DOI: 10.4251/wjgo.v12.i2.124] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Revised: 10/30/2019] [Accepted: 11/29/2019] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is a global problem affecting millions of people worldwide. This disease is unique because of its slow progress that makes it preventable and often curable. CRC symptoms usually emerge only at advanced stages of the disease, consequently its early detection can be achieved only through active population screening, which markedly reduces mortality due to this cancer. CRC screening tests that employ non-invasively detectable biomarkers are currently being actively developed and, in most cases, samples of either stool or blood are used. However, alternative biological substances that can be collected non-invasively (colorectal mucus, urine, saliva, exhaled air) have now emerged as new sources of diagnostic biomarkers. The main categories of currently explored CRC biomarkers are: (1) Proteins (comprising widely used haemoglobin); (2) DNA (including mutations and methylation markers); (3) RNA (in particular microRNAs); (4) Low molecular weight metabolites (comprising volatile organic compounds) detectable by metabolomic techniques; and (5) Shifts in gut microbiome composition. Numerous tests for early CRC detection employing such non-invasive biomarkers have been proposed and clinically studied. While some of these studies generated promising early results, very few of the proposed tests have been transformed into clinically validated diagnostic/screening techniques. Such DNA-based tests as Food and Drug Administration-approved multitarget stool test (marketed as Cologuard®) or blood test for methylated septin 9 (marketed as Epi proColon® 2.0 CE) show good diagnostic performance but remain too expensive and technically complex to become effective CRC screening tools. It can be concluded that, despite its deficiencies, the protein (haemoglobin) detection-based faecal immunochemical test (FIT) today presents the most cost-effective option for non-invasive CRC screening. The combination of non-invasive FIT and confirmatory invasive colonoscopy is the current strategy of choice for CRC screening. However, continuing intense research in the area promises the emergence of new superior non-invasive CRC screening tests that will allow the development of improved disease prevention strategies.
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Balavarca Y, Weigl K, Thomsen H, Brenner H. Performance of individual and joint risk stratification by an environmental risk score and a genetic risk score in a colorectal cancer screening setting. Int J Cancer 2020; 146:627-634. [PMID: 30868574 DOI: 10.1002/ijc.32272] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Revised: 02/26/2019] [Accepted: 03/08/2019] [Indexed: 02/05/2023]
Abstract
Early detection of colorectal neoplasms can reduce the disease burden of colorectal cancer by timely intervention of individuals at high risk. Our aim was to evaluate a joint environmental-genetic risk score as a risk stratification tool for early detection of advanced colorectal neoplasm (ACRN). Known environmental risk factors and high-risk genetic loci were summarized into risk scores for ACRN in 1014 eligible participants of a screening study. The performances of single and joint environmental-genetic scores were evaluated with estimates and 95% confidence intervals (CI) of the absolute risk, relative risk and predictive ability using the area under the curve (AUC). Individuals with higher environmental risk scores showed increasing ACRN risk, with 3.1-fold for intermediate risk and 4.8-fold for very high risk, compared to the very low environmental risk group. Similarly, individuals with higher genetic risk scores showed increasing ACRN risk, with 2.2-fold for intermediate risk and 3.5-fold for very high risk, compared to the lowest genetic risk group. Moreover, the joint environmental-genetic score improved the ACRN risk stratification and showed higher predictive values (AUC = 0.64; 95%CI = 0.60-0.67) with substantial difference (p = 0.0002) compared to the single environmental score (0.58; 0.55-0.62). The integration of environmental and genetic factors looks promising for improving targeting individuals at high-risk of colorectal neoplasm. Applications in practical screening programs require optimization with additional genetic and other biomarkers involved in colorectal carcinogenesis.
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Affiliation(s)
- Yesilda Balavarca
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Korbinian Weigl
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
- Medical Faculty, University of Heidelberg, Heidelberg, Germany
| | - Hauke Thomsen
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hermann Brenner
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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Pardini B, Sabo AA, Birolo G, Calin GA. Noncoding RNAs in Extracellular Fluids as Cancer Biomarkers: The New Frontier of Liquid Biopsies. Cancers (Basel) 2019; 11:E1170. [PMID: 31416190 PMCID: PMC6721601 DOI: 10.3390/cancers11081170] [Citation(s) in RCA: 141] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 08/04/2019] [Accepted: 08/10/2019] [Indexed: 02/06/2023] Open
Abstract
The last two decades of cancer research have been devoted in two directions: (1) understanding the mechanism of carcinogenesis for an effective treatment, and (2) improving cancer prevention and screening for early detection of the disease. This last aspect has been developed, especially for certain types of cancers, thanks also to the introduction of new concepts such as liquid biopsies and precision medicine. In this context, there is a growing interest in the application of alternative and noninvasive methodologies to search for cancer biomarkers. The new frontiers of the research lead to a search for RNA molecules circulating in body fluids. Searching for biomarkers in extracellular body fluids represents a better option for patients because they are easier to access, less painful, and potentially more economical. Moreover, the possibility for these types of samples to be taken repeatedly, allows a better monitoring of the disease progression or treatment efficacy for a better intervention and dynamic treatment of the patient, which is the fundamental basis of personalized medicine. RNA molecules, freely circulating in body fluids or packed in microvesicles, have all the characteristics of the ideal biomarkers owing to their high stability under storage and handling conditions and being able to be sampled several times for monitoring. Moreover, as demonstrated for many cancers, their plasma/serum levels mirror those in the primary tumor. There are a large variety of RNA species noncoding for proteins that could be used as cancer biomarkers in liquid biopsies. Among them, the most studied are microRNAs, but recently the attention of the researcher has been also directed towards Piwi-interacting RNAs, circular RNAs, and other small noncoding RNAs. Another class of RNA species, the long noncoding RNAs, is larger than microRNAs and represents a very versatile and promising group of molecules which, apart from their use as biomarkers, have also a possible therapeutic role. In this review, we will give an overview of the most common noncoding RNA species detectable in extracellular fluids and will provide an update concerning the situation of the research on these molecules as cancer biomarkers.
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Affiliation(s)
- Barbara Pardini
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy.
- Unit of Molecular Epidemiology and Exposome, Italian Institute for Genomic Medicine (IIGM), 10126 Turin, Italy.
| | - Alexandru Anton Sabo
- Department of Pediatrics, Marie Curie Emergency Clinical Hospital for Children, 077120 Bucharest, Romania
| | - Giovanni Birolo
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy
- Unit of Molecular Epidemiology and Exposome, Italian Institute for Genomic Medicine (IIGM), 10126 Turin, Italy
| | - George Adrian Calin
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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Jiang P, Han X, Zheng Y, Sui J, Bi W. Long non-coding RNA NKILA serves as a biomarker in the early diagnosis and prognosis of patients with colorectal cancer. Oncol Lett 2019; 18:2109-2117. [PMID: 31423284 DOI: 10.3892/ol.2019.10524] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Accepted: 05/17/2019] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer-associated mortality worldwide. The prognosis of patients with CRC at an advanced stage is poor. Biomarkers currently used in clinical practice, including carcinoembryonic antigen (CEA) and cancer antigen (CA) 19-9, lack sufficient sensitivity and specificity for early diagnosis and prediction, therefore there remains a requirement to improve the prognosis of patients with CRC. Long non-coding RNAs (lncRNAs) have been revealed to serve fundamental roles in various pathophysiological processes, including cancer initiation and progression. The present study investigated the expression and clinical significance of the lncRNA nuclear factor-κB interacting long non-coding RNA (NKILA) in CRC. It was identified that NKILA was downregulated in six CRC cell lines and tissues (n=173). Low NKILA expression was significantly associated with a poor differentiation grade, larger tumor size and advanced Tumor-Node-Metastases stages. Further statistical analyses revealed that low NKILA expression predicted poor overall survival (OS) rate and progression-free survival (PFS) rate. In addition, low NKILA expression was determined as an independent risk factor for poor OS and PFS. Furthermore, NKILA exhibited a relatively high sensitivity and specificity compared with CEA and CA19-9 in the early diagnosis of CRC. The serum level of NKILA was positively correlated with the level in tissues. In addition, a decreased NKILA level in serum was revealed to be partially restored post-operatively. In conclusion, low NKILA expression has been demonstrated to accelerate CRC progression and NKILA may be a potential novel biomarker in early diagnosis and prognosis of patients with CRC.
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Affiliation(s)
- Peng Jiang
- Department of Gastroenterology, The Central Hospital of Weihai, Weihai, Shandong 264400, P.R. China
| | - Xiaoting Han
- Department of General Surgery, The Central Hospital of Weihai, Weihai, Shandong 264400, P.R. China
| | - Yingnan Zheng
- Department of Gastroenterology, The Central Hospital of Rizhao, Shandong 276800, P.R. China
| | - Jianchao Sui
- Department of Gastroenterology, The Central Hospital of Weihai, Weihai, Shandong 264400, P.R. China
| | - Weiping Bi
- Department of Gastroenterology, The Central Hospital of Weihai, Weihai, Shandong 264400, P.R. China
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Vymetalkova V, Vodicka P, Vodenkova S, Alonso S, Schneider-Stock R. DNA methylation and chromatin modifiers in colorectal cancer. Mol Aspects Med 2019; 69:73-92. [PMID: 31028771 DOI: 10.1016/j.mam.2019.04.002] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 04/11/2019] [Accepted: 04/15/2019] [Indexed: 12/15/2022]
Abstract
Colorectal carcinogenesis is a multistep process involving the accumulation of genetic alterations over time that ultimately leads to disease progression and metastasis. Binding of transcription factors to gene promoter regions alone cannot explain the complex regulation pattern of gene expression during this process. It is the chromatin structure that allows for a high grade of regulatory flexibility for gene expression. Posttranslational modifications on histone proteins such as acetylation, methylation, or phosphorylation determine the accessibility of transcription factors to DNA. DNA methylation, a chemical modification of DNA that modulates chromatin structure and gene transcription acts in concert with these chromatin conformation alterations. Another epigenetic mechanism regulating gene expression is represented by small non-coding RNAs. Only very recently epigenetic alterations have been included in molecular subtype classification of colorectal cancer (CRC). In this chapter, we will provide examples of the different epigenetic players, focus on their role for epithelial-mesenchymal transition and metastatic processes and discuss their prognostic value in CRC.
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Affiliation(s)
- Veronika Vymetalkova
- Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 00 Prague, Czech Republic; Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Albertov 4, 128 00, Prague, Czech Republic; Biomedical Centre, Faculty of Medicine in Pilsen, Charles University in Prague, 323 00, Pilsen, Czech Republic
| | - Pavel Vodicka
- Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 00 Prague, Czech Republic; Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Albertov 4, 128 00, Prague, Czech Republic; Biomedical Centre, Faculty of Medicine in Pilsen, Charles University in Prague, 323 00, Pilsen, Czech Republic
| | - Sona Vodenkova
- Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 00 Prague, Czech Republic; Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Albertov 4, 128 00, Prague, Czech Republic
| | - Sergio Alonso
- Program of Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute, (IGTP-PMPPC), Campus Can Ruti, 08916, Badalona, Barcelona, Spain
| | - Regine Schneider-Stock
- Experimental Tumorpathology, Institute of Pathology, University Hospital of Friedrich-Alexander-University Erlangen-Nürnberg, Universitätsstrasse 22, 91054, Erlangen, Germany.
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Francavilla A, Tarallo S, Pardini B, Naccarati A. Fecal microRNAs as non-invasive biomarkers for the detection of colorectal cancer: a systematic review. MINERVA BIOTECNOL 2019; 31. [DOI: 10.23736/s1120-4826.18.02495-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Han B, Feng D, Yu X, Zhang Y, Liu Y, Zhou L. Identification and Interaction Analysis of Molecular Markers in Colorectal Cancer by Integrated Bioinformatics Analysis. Med Sci Monit 2018; 24:6059-6069. [PMID: 30168505 PMCID: PMC6129036 DOI: 10.12659/msm.910106] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is an extremely common gastrointestinal malignancy. MATERIAL AND METHODS Three mRNA and 2 microRNA microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and microRNAs (DEMs) were obtained. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) program was utilized to perform gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Protein-protein interaction (PPI) network analysis was performed with the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape and Molecular Complex Detection (MCODE). Kaplan-Meier curves were plotted to determine overall survival (OS) estimates. DEMs targets were predicted by miRWalk. Quantitative reverse transcription polymerase chain reaction (QRT-PCR) was utilized to detect the expression of genes and microRNAs. RESULTS A total of 264 DEGs and 8 DEMs were obtained. GO analysis revealed that the DEGs were enriched in terms of cell structure, digestion, receptor binding, and extracellular material (ECM). KEGG pathway analysis showed that the DEGs were enriched in ECM interaction and mineral absorption. Additionally, a PPI network consisting of 181 nodes and 450 edges was established. Three modules with 38 high-degree hubs were extracted from the PPI network and found to be involved in pathways such as chemokine signaling. Five DEGs located in the network of DEM-DEG pairs were associated with the overall survival of CRC patients. Furthermore, hsa-miR-551b was demonstrated to be significantly down-regulated in CRC tissues. CONCLUSIONS The key biomarkers could provide new clues for CRC.
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Affiliation(s)
- Bin Han
- Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China (mainland).,Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China (mainland).,Health Service Center of Southeast Community, Nanchong, Sichuan, China (mainland)
| | - Dan Feng
- Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China (mainland)
| | - Xin Yu
- Health Service Center of Southeast Community, Nanchong, Sichuan, China (mainland)
| | - Yuanyuan Zhang
- Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China (mainland)
| | - Yuanqi Liu
- Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China (mainland).,Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China (mainland)
| | - Liming Zhou
- Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China (mainland)
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Application of Fecal Volatile Organic Compound Analysis in Clinical Practice: Current State and Future Perspectives. CHEMOSENSORS 2018. [DOI: 10.3390/chemosensors6030029] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Increasing interest is noticed in the potential of volatile organic compound (VOC) analysis as non-invasive diagnostic biomarker in clinical medical practice. The spectrum of VOCs, originating from (patho)physiological metabolic processes in the human body and detectable in bodily excrements, such as exhaled breath, urine and feces, harbors a magnificent source of information. Thus far, the majority of studies have focused on VOC analysis in exhaled breath, aiming at identification of disease-specific VOC profiles. Recently, an increasing number of studies have evaluated the usability of VOC present in the headspace of feces in the diagnostic work-up of a wide range of gastrointestinal diseases. Promising results have been demonstrated particularly in those diseases in which microbiota alterations are considered to play a significant etiological role, such as colorectal carcinoma, inflammatory bowel disease, irritable bowel syndrome, celiac disease and infectious bowel diseases. In addition, fecal VOC analysis seems to have potential as a diagnostic biomarker for extra-intestinal diseases, including bronchopulmonary dysplasia and sepsis. Different methods for VOC analysis have been used in medical studies, such as gas-chromatography mass spectrometry, selected-ion flow tube-mass spectrometry, ion-mobility spectrometry, and electronic nose devices. In this review, the available literature on the potential of fecal VOCs as diagnostic biomarker, including an overview of relevant VOC detection techniques, is discussed. In addition, future hurdles, which need to be taken prior to implementation of VOC analysis in daily clinical practice, are outlined.
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Ding D, Li C, Zhao T, Li D, Yang L, Zhang B. LncRNA H19/miR-29b-3p/PGRN Axis Promoted Epithelial-Mesenchymal Transition of Colorectal Cancer Cells by Acting on Wnt Signaling. Mol Cells 2018; 41:423-435. [PMID: 29754471 PMCID: PMC5974619 DOI: 10.14348/molcells.2018.2258] [Citation(s) in RCA: 99] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Revised: 12/30/2017] [Accepted: 01/14/2018] [Indexed: 02/07/2023] Open
Abstract
This investigation was aimed at working out the combined role of lncRNA H19, miR-29b and Wnt signaling in the development of colorectal cancer (CRC). In the aggregate, 185 CRC tissues and corresponding para-carcinoma tissues were gathered. The human CRC cell lines (i.e. HT29, HCT116, SW480 and SW620) and normal colorectal mucosa cell line (NCM460) were also purchased. Si-H19, si-NC, miR-29b-3p mimics, miR-29b-3p inhibitor, si-PGRN and negative control (NC) were, respectively, transfected into the CRC cells. Lucif-erase reporter plasmids were prepared to evaluate the transduction activity of Wnt/β-catenin signaling pathway, and dual-luciferase reporter gene assay was arranged to confirm the targeted relationship between H19 and miR-29b-3p, as well as between miR-29b-3p and PGRN. Finally, the proliferative and invasive capacities of CRC cells were appraised through transwell, MTT and scratch assays. As a result, over-expressed H19 and down-expressed miR-29b-3p displayed close associations with the CRC patients' poor prognosis (P < 0.05). Besides, transfection with si-H19, miR-29b-3p mimic or si-PGRN were correlated with elevated E-cadherin expression, decreased snail and vimentin expressions, as well as less-motivated cell proliferation and cell metastasis (P < 0.05). Moreover, H19 was verified to directly target miR-29b-3p based on the luciferase reporter gene assay (P < 0.05), and miR-29b-3p also bound to PGRN in a direct manner (P < 0.05). Finally, addition of LiCl (Wnt/β-catenin pathway activator) or XAV93920 (Wnt/β-catenin pathway inhibitor) would cause remarkably altered E-cadherin, c-Myc, vimentin and snail expressions, as well as significantly changed transcriptional activity of β-catenin/Tcf reporter plasmid (P < 0.05). In conclusion, the lncRNA H19/miR-29b-3p/PGRN/Wnt axis counted a great deal for seeking appropriate diagnostic biomarkers and treatment targets for CRC.
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Affiliation(s)
- Dayong Ding
- Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033,
P.R. China
| | - Changfeng Li
- Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033,
P.R. China
| | - Tiancheng Zhao
- Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033,
P.R. China
| | - Dandan Li
- Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033,
P.R. China
| | - Lei Yang
- Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033,
P.R. China
| | - Bin Zhang
- Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033,
P.R. China
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Li H, Ma SQ, Huang J, Chen XP, Zhou HH. Roles of long noncoding RNAs in colorectal cancer metastasis. Oncotarget 2018; 8:39859-39876. [PMID: 28418892 PMCID: PMC5503659 DOI: 10.18632/oncotarget.16339] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Accepted: 02/20/2017] [Indexed: 12/11/2022] Open
Abstract
Colorectal cancer (CRC) is the 3rd most common malignancies worldwide. Metastasis is responsible for more than 90% CRC patients' death. Long noncoding RNAs (lncRNAs) are an important class of transcribed RNA molecules greater than 200 nucleotides in length. With the development of whole genome sequencing technologies, they have been gained more attention. Accumulating evidences suggest that abnormal expression of lncRNAs in diverse diseases are involved in various biological functions such as proliferation, apoptosis, metastasis and differentiation by acting as epigenetic, splicing, transcriptional or post-transcriptional regulators. Aberrant expression of lncRNAs has also been found in CRC. Besides, recent studies have indicated that lncRNAs play important roles in tumourigenesis and cancer metastasis. They participate in the process of metastasis by activing or inhibiting the metastatic pathways. However, their functions on the development of cancer metastasis are poorly understood. In this review, we highlight the findings of roles for lncRNAs in CRC metastasis and review the metastatic pathways of lncRNAs leading to cancer metastasis in CRC, including escape of apoptosis, epithelial-mesenchymal transition (EMT), angiogenesis and invasion, migration and proliferation. Furthermore, we also discuss the potential clinical application of lncRNAs in CRC as diagnostic markers and therapeutic targets.
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Affiliation(s)
- He Li
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P.R. China.,Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, P.R. China
| | - Si-Qing Ma
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P.R. China.,Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, P.R. China
| | - Jin Huang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P.R. China.,Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, P.R. China
| | - Xiao-Ping Chen
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P.R. China.,Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, P.R. China.,Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, P. R. China
| | - Hong-Hao Zhou
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P.R. China.,Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, P.R. China.,Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, P. R. China
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Wu K, Xu K, Liu K, Huang J, Chen J, Zhang J, Zhang N. Long noncoding RNA BC200 regulates cell growth and invasion in colon cancer. Int J Biochem Cell Biol 2018; 99:219-225. [PMID: 29625226 DOI: 10.1016/j.biocel.2018.04.001] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 03/13/2018] [Accepted: 04/02/2018] [Indexed: 12/31/2022]
Abstract
Colon cancer is the third most commonly diagnosed and deadly cancer worldwide. Efforts have been made to characterize its pathological mechanisms and to explore new therapeutic targets of this disease. Aberrant expression of long noncoding RNAs (lncRNAs) has been associated with the pathogenesis of colon cancer. In the current study, we aimed to define the biological mechanism of the lncRNA BC200 in colon cancer. Here, we found that expression of BC200 was up-regulated in colon cancer tissues as compared with adjacent non-cancerous tissues. The BC200 level was positively correlated with advanced TNM stage. The Kaplan-Meier method indicated that the cumulative survival rate was significantly lower in patients with high BC200 expression than in those with low BC200 expression. Interestingly, we found that knockdown of BC200 inhibited proliferation of HCT-116 and HT29 colon cancer cell lines and reduce the expression of cell proliferation markers, such as Ki-67 and PCNA. In addition, silencing of BC200 could induce obvious G0/G1 arrest and cause apoptosis in HCT-116 and HT29 cells and reduced the expression of cyclin D1, cyclin E, and c-Myc through inhibiting the expression of β-catenin. Importantly, we found that knockdown of BC200 reduced invasion of HCT-116 and HT29 cells and epithelial-mesenchymal transition (EMT) by reducing the expression of MMP-2 and MMP-9. Mechanistically, silencing of BC200 significantly reduced the phosphorylation of STAT3. Overall, the findings presented here suggest that lncRNA BC200 may serve as a novel oncogene and a new therapeutic target for colon cancer.
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Affiliation(s)
- Kaiming Wu
- Gastrointestinal Surgery Center, 1st Affiliated Hospital of Sun Yat-Sen Univesity, Guangzhou, Guangdong, 510000, PR China
| | - Kaiwu Xu
- Gastrointestinal Surgery Center, 1st Affiliated Hospital of Sun Yat-Sen Univesity, Guangzhou, Guangdong, 510000, PR China
| | - Kuanzhi Liu
- Gastrointestinal Surgery Center, 1st Affiliated Hospital of Sun Yat-Sen Univesity, Guangzhou, Guangdong, 510000, PR China
| | - Jiehong Huang
- School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, PR China
| | - Jianhui Chen
- Gastrointestinal Surgery Center, 1st Affiliated Hospital of Sun Yat-Sen Univesity, Guangzhou, Guangdong, 510000, PR China
| | - Jian Zhang
- Gastrointestinal Surgery Center, 1st Affiliated Hospital of Sun Yat-Sen Univesity, Guangzhou, Guangdong, 510000, PR China
| | - Ning Zhang
- Department of Gastroenterology and Hepatology, 1st Affiliated Hospital of Sun Yat-Sen Univesity, Guangzhou, Guangdong, 510000, PR China.
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Wu L, Chang L, Wang H, Ma W, Peng Q, Yuan Y. Clinical significance of C/D box small nucleolar RNA U76 as an oncogene and a prognostic biomarker in hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2018; 42:82-91. [PMID: 28578939 DOI: 10.1016/j.clinre.2017.04.018] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 04/06/2017] [Accepted: 04/26/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Recent evidence has suggested novel roles of small nucleolar RNAs (snoRNAs) in tumorigenicity. However, the roles of C/D box snoRNA U76 (SNORD76) in the development of hepatocellular carcinoma (HCC) remain unknown. Herein, we systematically evaluated dysregulation of snoRNAs in HCC and clarified the biomarker potential and biological significance of SNORD76 in HCC. METHODS We performed quantitative analyses of the expression of SNORD76 in 66 HCC specimens to compare its expression pattern between tumor tissue and matched non-tumor tissue. The effects of SNORD76 on HCC tumorigenicity were investigated in SK-Hep1 and Huh7 cells as well as in a xenograft nude mouse model. RESULTS SNORD76 expression was significantly upregulated in HCC tissues compared to corresponding non-tumor tissues. This upregulation of SNORD76 in HCC tumors was significantly associated with poorer patient survival. Furthermore, inhibiting SNORD76 expression suppressed cell proliferation by inducing G0/G1 cell cycle arrest and apoptosis. Low SNORD76 expression also resulted in decreased HCC growth in an animal model. Conversely, overexpressing SNORD76 promoted cell proliferation. SNORD76 increased HCC cell invasion by inducing epithelial-mesenchymal transition (EMT). Finally, we found that SNORD76 promoted HCC tumorigenicity through activation of the Wnt/β-catenin pathway. CONCLUSIONS Therefore, we demonstrated for the first time that SNORD76 may function as a novel tumor promoter in HCC and may serve as a promising prognostic biomarker in patients with HCC.
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Affiliation(s)
- Long Wu
- Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan 430071, PR China
| | - Lei Chang
- Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan 430071, PR China
| | - Haitao Wang
- Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan 430071, PR China
| | - Weijie Ma
- Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan 430071, PR China
| | - Qin Peng
- Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan 430071, PR China
| | - Yufeng Yuan
- Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan 430071, PR China.
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Simonian M, Sharifi M, Nedaeinia R, Mosallaie M, Khosravi S, Avan A, Ghayour-Mobarhan M, Bagheri H, Salehi R. Evaluation of miR-21 Inhibition and its Impact on Cancer Susceptibility Candidate 2 Long Noncoding RNA in Colorectal Cancer Cell Line. Adv Biomed Res 2018; 7:14. [PMID: 29456985 PMCID: PMC5812095 DOI: 10.4103/abr.abr_214_16] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background: Both microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have been shown to have a critical role in the regulation of cellular processes such as cell growth and apoptosis, as well as cancer progression and metastasis. lncRNAs are aberrantly expressed in many diseases including cancer. Although it is well known that miRNAs can target a large number of protein-coding genes, little is known whether miRNAs can also target lncRNAs. In the present study, we determine whether miR-21 can regulate lncRNA cancer susceptibility candidate 2 (CASC2) in colorectal cancer. Materials and Methods: LS174T cells were transfected with locked nucleic acid (LNA)-anti-miR-21 and scrambled LNA for 24, 48 and 72 h. The expression of miR-21 and lncCASC2 was evaluated by quantitative reverse transcriptase polymerase chain reaction. Results: However, contrary to what we expected and reported by others, lncCASC2 quantity was significantly reduced in LNA treated LS174T cells compared to the scrambled treated and normal untreated cells (P < 0.05). Conclusion: The interaction of miRNA and lncRNA are not as simple as suggested by other reports. Moreover, it could be complex molecular mechanisms underlying the communication of various noncoding RNA elements.
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Affiliation(s)
- Miganoosh Simonian
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammadreza Sharifi
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Reza Nedaeinia
- Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Mosallaie
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Sharifeh Khosravi
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amir Avan
- Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- Biochemistry of Nutrition Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hadi Bagheri
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Rasoul Salehi
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.,Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.,Gerfa Namayesh Azmayesh (GENAZMA) Science and Research Institute, Isfahan, Iran
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Yu B, Du Q, Li H, Liu HY, Ye X, Zhu B, Zhai Q, Li XX. Diagnostic potential of serum exosomal colorectal neoplasia differentially expressed long non-coding RNA (CRNDE-p) and microRNA-217 expression in colorectal carcinoma. Oncotarget 2017; 8:83745-83753. [PMID: 29137379 PMCID: PMC5663551 DOI: 10.18632/oncotarget.19407] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Accepted: 07/12/2017] [Indexed: 02/07/2023] Open
Abstract
In this study, we investigated the diagnostic potential of serum exosomal colorectal neoplasia differentially expressed (CRNDE-p) long coding RNA and microRNA-217 in colorectal carcinoma (CRC). We detected high CRNDE-p and low miR-217 levels in exosomes released by multiple CRC cell lines into culture media as well as in sera from CRC xenograft mice and CRC patients. Conversely, we observed lower CRNDE-p and higher miR-217 levels in serum exosomes from post-chemotherapy than from pre-chemotherapy patient samples. The area under curve (AUC) value for the serum exosomal CRNDE-p and miR-217 combination was higher than CRNDE-p or miR-217 alone. Moreover, high CRNDE-p and low miR-217 serum exosomal levels correlated with advanced clinical stages (III/IV), tumor classification (T3/T4), and lymph node or distant metastasis. Thus combined evaluation of serum exosomal CRNDE-p and miR-217 levels show diagnostic and prognostic potential for CRC patients.
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Affiliation(s)
- Bo Yu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.,Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Qiong Du
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.,Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Huan Li
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.,Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Hong-Yue Liu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.,Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Xuan Ye
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.,Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Bin Zhu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.,Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Qing Zhai
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.,Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Xin-Xiang Li
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.,Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
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45
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Li LL, Qu LL, Fu HJ, Zheng XF, Tang CH, Li XY, Chen J, Wang WX, Yang SX, Wang L, Zhao GH, Lv PP, Zhang M, Lei YY, Qin HF, Wang H, Gao HJ, Liu XQ. Circulating microRNAs as novel biomarkers of ALK-positive nonsmall cell lung cancer and predictors of response to crizotinib therapy. Oncotarget 2017; 8:45399-45414. [PMID: 28514730 PMCID: PMC5542196 DOI: 10.18632/oncotarget.17535] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Accepted: 04/12/2017] [Indexed: 01/09/2023] Open
Abstract
Circulating microRNAs are potential diagnostic and predictive biomarkers, but have not been investigated for patients with anaplastic lymphoma kinase (ALK)-positive lung cancer. In this exploratory study, we sought to identify potential plasma biomarkers for ALK-positive non-small cell lung cancer (NSCLC). A microRNA microarray was used to select ALK-related microRNAs in ALK-positive NSCLC (n = 3), ALK-negative NSCLC (n = 3), and healthy subjects (n = 3). Plasma levels of 21 microRNAs were differentially expressed for ALK-positive and ALK-negative NSCLC, including 14 down-regulated and 7 up-regulated microRNAs. We also identified 5s rRNA as the most stable endogenous control gene using geNorm and NormFinder algorithms. Candidate microRNAs in plasma from ALK-positive (n = 41) and ALK-negative NSCLC patients (n = 32) were quantified using real-time reverse transcriptase quantitative polymerase chain reaction. The expression levels of miR-28-5p, miR-362-5p, and miR-660-5p were all down-regulated in ALK-positive NSCLC, compared with ALK-negative NSCLC. The areas under the receiver operating characteristic curves of miR-28-5p, miR-362-5p, miR-660-5p, and 3-microRNAs panel were 0.873, 0.673, 0.760, and 0.876, respectively. The positive predictive values of miR-28-5p, miR-362-5p, and miR-660-5p were 96.43%, 80.77%, and 83.87%, respectively. Increased plasma levels of miR-660-5p after crizotinib treatment predicted good tumor response (p = 0.012). The pre-crizotinib levels of miR-362-5p were significantly associated with progression-free survival (p = 0.015). Thus, in this preliminary investigation, we identified a potential panel of 3 microRNAs for distinguishing between patients with ALK-positive and ALK-negative NSCLC. We also identified miR-660-5p and miR-362-5p as potential predictors for response to crizotinib treatment.
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Affiliation(s)
- Liang-Liang Li
- Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China
- Department of Oncology, 309th Hospital of PLA, Beijing, China
| | - Li-Li Qu
- Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China
| | - Han-Jiang Fu
- Department of Biochemistry and Molecular Biology, Beijing Institute of Radiation Medicine, Beijing, China
| | - Xiao-Fei Zheng
- Department of Biochemistry and Molecular Biology, Beijing Institute of Radiation Medicine, Beijing, China
| | - Chuan-Hao Tang
- Department of Oncology, Peking University International Hospital, Beijing, China
| | - Xiao-Yan Li
- Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China
| | - Jian Chen
- Department of Respiratory, Affiliated Hospital of Aviation Medicine, Beijing, China
| | - Wei-Xia Wang
- Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China
| | - Shao-Xing Yang
- Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China
| | - Lin Wang
- Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China
| | - Guan-Hua Zhao
- Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China
| | - Pan-Pan Lv
- Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China
| | - Min Zhang
- Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China
| | - Yang-Yang Lei
- Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China
| | - Hai-Feng Qin
- Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China
| | - Hong Wang
- Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China
| | - Hong-Jun Gao
- Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China
| | - Xiao-Qing Liu
- Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China
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