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Saadh MJ, Allela OQB, Kareem RA, Baldaniya L, Ballal S, Vashishth R, Parmar M, Sameer HN, Hamad AK, Athab ZH, Adil M. Prognostic gene expression profile of colorectal cancer. Gene 2025; 955:149433. [PMID: 40122415 DOI: 10.1016/j.gene.2025.149433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 02/26/2025] [Accepted: 03/18/2025] [Indexed: 03/25/2025]
Abstract
Colorectal cancer is a major global health burden, with significant heterogeneity in clinical outcomes among patients. Identifying robust prognostic gene expression signatures can help stratify patients, guide treatment decisions, and improve clinical management. This review provides an overview of current prognostic gene expression profiles in colorectal cancer research. We have synthesized evidence from numerous published studies investigating the association between tumor gene expression patterns and patient survival outcomes. The reviewed literature reveals several promising gene signatures that have demonstrated the ability to predict disease-free survival and overall survival in CRC patients, independent of standard clinicopathological risk factors. These genes are crucial in fundamental biological processes, including cell cycle control, epithelial-mesenchymal transition, and immune regulation. The implementation of prognostic gene expression tests in clinical practice holds great potential for enabling more personalized management strategies for colorectal cancer.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman 11831, Jordan.
| | | | | | - Lalji Baldaniya
- Marwadi University Research Center, Department of Pharmacy, Faculty of Health Sciences, Marwadi University, Rajkot 360003 Gujarat, India.
| | - Suhas Ballal
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India.
| | - Raghav Vashishth
- Department of Surgery, National Institute of Medical Sciences, NIMS University Rajasthan, Jaipur, India.
| | - Manisha Parmar
- Chandigarh Pharmacy College, Chandigarh Group of Colleges-Jhanjeri, Mohali, Punjab, India.
| | - Hayder Naji Sameer
- Collage of Pharmacy, National University of Science and Technology, Dhi Qar 64001, Iraq.
| | | | - Zainab H Athab
- Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq.
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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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Shakerian N, Tafazoli A, Razavinia A, Sadrzadeh Aghajani Z, Bana N, Mard-Soltani M, Khalesi B, Hashemi ZS, Khalili S. Current Understanding of Therapeutic and Diagnostic Applications of Exosomes in Pancreatic Cancer. Pancreas 2025; 54:e255-e267. [PMID: 39661050 DOI: 10.1097/mpa.0000000000002414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2024]
Abstract
ABSTRACT Unusual symptoms, rapid progression, lack of reliable early diagnostic biomarkers, and lack of efficient treatment choices are the ongoing challenges of pancreatic cancer. Numerous research studies have demonstrated the correlation between exosomes and various aspects of pancreatic cancer. In light of these facts, exosomes possess the potential to play functional roles in the treatment, prognosis, and diagnosis of the pancreatic cancer. In the present study, we reviewed the most recent developments in approaches for exosome separation, modification, monitoring, and communication. Moreover, we discussed the clinical uses of exosomes as less invasive liquid biopsies and drug carriers and their contribution to the control of angiogenic activity of pancreatic cancer. Better investigation of exosome biology would help to effectively engineer therapeutic exosomes with certain nucleic acids, proteins, and even exogenous drugs as their cargo. Circulating exosomes have shown promise as reliable candidates for pancreatic cancer early diagnosis and monitoring in high-risk people without clinical cancer manifestation. Although we have tried to reflect the status of exosome applications in the treatment and detection of pancreatic cancer, it is evident that further studies and clinical trials are required before exosomes may be employed as a routine therapeutic and diagnostic tools for pancreatic cancer.
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Affiliation(s)
- Neda Shakerian
- From the Department of Clinical Biochemistry, Faculty of Medical Sciences, Dezful University of Medical Sciences, Dezful
| | - Aida Tafazoli
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz
| | - Amir Razavinia
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, IR
| | | | - Nikoo Bana
- Kish International Campus, University of Teheran
| | - Maysam Mard-Soltani
- From the Department of Clinical Biochemistry, Faculty of Medical Sciences, Dezful University of Medical Sciences, Dezful
| | - Bahman Khalesi
- Department of Research and Production of Poultry Viral Vaccine, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj
| | - Zahra Sadat Hashemi
- ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran
| | - Saeed Khalili
- Department of Biology Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran
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Avasthi KK, Choi JW, Glushko T, Manley BJ, Yu A, Park JY, Brown JS, Pow-Sang J, Gantenby R, Wang L, Balagurunathan Y. Extracellular Microvesicle MicroRNAs and Imaging Metrics Improve the Detection of Aggressive Prostate Cancer: A Pilot Study. Cancers (Basel) 2025; 17:835. [PMID: 40075682 PMCID: PMC11898942 DOI: 10.3390/cancers17050835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 02/24/2025] [Accepted: 02/25/2025] [Indexed: 03/14/2025] Open
Abstract
Background/Objectives: Prostate cancer (PCa) is the most diagnosed cancer in men worldwide. Early diagnosis of the disease provides better treatment options for these patients. Recent studies have demonstrated that plasma-based extracellular vesicle microRNAs (miRNAs) are functionally linked to cancer progression, metastasis, and aggressiveness. The use of magnetic resonance imaging (MRI) as the standard of care provides an overall assessment of prostate disease. Quantitative metrics (radiomics) from the MRI provide a better evaluation of the tumor and have been shown to improve disease detection. Methods: We conducted a study on prostate cancer patients, analyzing baseline blood plasma and MRI data. Exosomes were isolated from blood plasma samples to quantify miRNAs, while MRI scans provided detailed tumor morphology. Radiomics features from MRI and miRNA expression data were integrated to develop predictive models, which were evaluated using ROC curve analysis, highlighting the multivariable model's effectiveness. Results: Our findings indicate that the univariate feature-based model with the highest Youden's index achieved average areas under the receiver operating characteristic (ROC) curve of 0.76, 0.82, and 0.84 for miRNA, MR-T2W, and MR-ADC features, respectively, in identifying clinically aggressive (Gleason grade) disease. The multivariable feature-based model yielded an average area under the curve (AUC) of 0.88 and 0.95 using combinations of miRNA markers with imaging features in MR-ADC and MR-T2W, respectively. Conclusions: Our study demonstrates that combining miRNA markers with MRI-based radiomics improves the identification of clinically aggressive prostate cancer.
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Affiliation(s)
- Kapil K. Avasthi
- Department of Tumor Microenvironment and Metastasis, Moffitt Cancer Center, Tampa, FL 33612, USA;
| | - Jung W. Choi
- Department of Diagnostic & Interventional Radiology, Moffitt Cancer Center, Tampa, FL 33612, USA; (J.W.C.); (R.G.)
| | - Tetiana Glushko
- Department of Diagnostic & Interventional Radiology, Moffitt Cancer Center, Tampa, FL 33612, USA; (J.W.C.); (R.G.)
| | - Brandon J. Manley
- Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA; (B.J.M.); (A.Y.); (J.P.-S.)
| | - Alice Yu
- Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA; (B.J.M.); (A.Y.); (J.P.-S.)
| | - Jong Y. Park
- Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL 33612, USA;
| | - Joel S. Brown
- Department of Mathematical Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA;
| | - Julio Pow-Sang
- Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA; (B.J.M.); (A.Y.); (J.P.-S.)
| | - Robert Gantenby
- Department of Diagnostic & Interventional Radiology, Moffitt Cancer Center, Tampa, FL 33612, USA; (J.W.C.); (R.G.)
| | - Liang Wang
- Department of Tumor Microenvironment and Metastasis, Moffitt Cancer Center, Tampa, FL 33612, USA;
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Zhang J, Luo C, Long H, Zhang B, Shan H, Hou B. Circulating exosomal miRNA-451 as an effective diagnostic biomarker and prognostic indicator for multiple myeloma. Int J Biol Markers 2024; 39:301-309. [PMID: 39311052 DOI: 10.1177/03936155241283747] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/06/2024]
Abstract
OBJECTIVE Multiple myeloma (MM) is a plasma cell malignancy characterized by abnormal plasma cell proliferation in the bone marrow. Circulating exosomal miRNA-451 is associated with the progression of many tumors, but the relationship between its expression and MM has not been reported. In this study, we aimed to investigate the clinical value of miRNA-451 as a biomarker for diagnosis and prognosis of multiple myeloma. METHODS A total of 120 patients with multiple myeloma and 120 healthy control people were recruited in this study. The miRNA-451 expression in serum exosomes of participants was measured by quantitative real-time polymerase chain reaction, and the diagnostic value of miRNA-451 for multiple myeloma was assessed by receiver operating characteristic (ROC) curve. The correlation between miRNA-451 expression and plasma cells ratio and M protein content was analyzed by Pearson correlation coefficient. The prognosis of different miRNA-451 expression was evaluated by survival curves. RESULTS Results suggested that serum exosomal miRNA-451 expression was significantly decreased in patients with multiple myeloma rather than in the healthy controls. The ROC curve showed that area under the curve value of miRNA-451 was 0.888, suggesting that miRNA-451 had diagnostic value to multiple myeloma. Moreover, there was a negative correlation between miRNA-451 expression and plasma cells ratio or M protein content. Survival curves showed that patients with high miRNA-451 expression had a longer survival time, suggesting the value of miRNA-451 as a prognostic indicator of multiple myeloma. CONCLUSION We demonstrated the relationship between miRNA-451 expression and multiple myeloma, indicating that miRNA-451 in circulating exosomes may be an effective diagnostic biomarker and prognostic indicator for multiple myeloma.
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Affiliation(s)
- Jun Zhang
- Department of Hematology, the Second Affiliated Hospital of Guizhou Medical University, No. 3 Kangfu Road, Kaili City, Guizhou Province, 556000, China
| | - Cheng Luo
- Department of Hematology, the Second Affiliated Hospital of Guizhou Medical University, No. 3 Kangfu Road, Kaili City, Guizhou Province, 556000, China
| | - Haiying Long
- Department of Hematology, the Second Affiliated Hospital of Guizhou Medical University, No. 3 Kangfu Road, Kaili City, Guizhou Province, 556000, China
| | - Bin Zhang
- Department of Hematology, the Second Affiliated Hospital of Guizhou Medical University, No. 3 Kangfu Road, Kaili City, Guizhou Province, 556000, China
| | - Hongtao Shan
- Department of Hematology, the Second Affiliated Hospital of Guizhou Medical University, No. 3 Kangfu Road, Kaili City, Guizhou Province, 556000, China
| | - Benli Hou
- Department of Hematology, the Second Affiliated Hospital of Guizhou Medical University, No. 3 Kangfu Road, Kaili City, Guizhou Province, 556000, China
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Ždralević M, Radović A, Raonić J, Popovic N, Klisic A, Vučković L. Advances in microRNAs as Emerging Biomarkers for Colorectal Cancer Early Detection and Diagnosis. Int J Mol Sci 2024; 25:11060. [PMID: 39456841 PMCID: PMC11507567 DOI: 10.3390/ijms252011060] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 09/21/2024] [Accepted: 09/27/2024] [Indexed: 10/26/2024] Open
Abstract
Colorectal cancer (CRC) remains the second most common cause of cancer-related mortality worldwide, necessitating advancements in early detection and innovative treatment strategies. MicroRNAs (miRNAs), small non-coding RNAs involved in gene regulation, have emerged as crucial players in the pathogenesis of CRC. This review synthesizes the latest findings on miRNA deregulated in precancerous lesions and in CRC. By examining the deregulation patterns of miRNAs across different stages of CRC development, this review highlights their potential as diagnostic tools. We specifically analyse the roles and diagnostic relevance of four miRNAs-miR-15b, miR-21, miR-31, and miR-146a-that consistently exhibit altered expression in CRC. The current knowledge of their role in key oncogenic pathways, drug resistance, and clinical relevance is discussed. Despite challenges posed by the heterogeneity of the research findings on miRNA deregulation and their role in CRC, integrating miRNA diagnostics into current screening methods holds promise for enhancing personalized medicine approaches. This review emphasizes the transformative potential of miRNAs in CRC diagnosis, paving the way for improved patient outcomes and novel therapeutic paradigms.
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Affiliation(s)
- Maša Ždralević
- Institute for Advanced Studies, University of Montenegro, Cetinjska 2, 81000 Podgorica, Montenegro
| | - Andrijana Radović
- Faculty of Medicine, University of Montenegro, Kruševac bb, 81000 Podgorica, Montenegro (N.P.); (A.K.); (L.V.)
| | - Janja Raonić
- Center for Pathology, Clinical Center of Montenegro, Ljubljanska bb, 81000 Podgorica, Montenegro;
| | - Natasa Popovic
- Faculty of Medicine, University of Montenegro, Kruševac bb, 81000 Podgorica, Montenegro (N.P.); (A.K.); (L.V.)
| | - Aleksandra Klisic
- Faculty of Medicine, University of Montenegro, Kruševac bb, 81000 Podgorica, Montenegro (N.P.); (A.K.); (L.V.)
- Center for Laboratory Diagnostics, Primary Health Care Center, 81000 Podgorica, Montenegro
| | - Ljiljana Vučković
- Faculty of Medicine, University of Montenegro, Kruševac bb, 81000 Podgorica, Montenegro (N.P.); (A.K.); (L.V.)
- Center for Pathology, Clinical Center of Montenegro, Ljubljanska bb, 81000 Podgorica, Montenegro;
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AlZaabi A, Shalaby A. A Systematic Review of Diagnostic Performance of Circulating MicroRNAs in Colorectal Cancer Detection with a Focus on Early-Onset Colorectal Cancer. Int J Mol Sci 2024; 25:9565. [PMID: 39273512 PMCID: PMC11394782 DOI: 10.3390/ijms25179565] [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: 08/07/2024] [Revised: 08/19/2024] [Accepted: 08/20/2024] [Indexed: 09/15/2024] Open
Abstract
The rising incidence and mortality of early-onset colorectal cancer (EOCRC) emphasize the urgent need for effective non-invasive screening. Circulating microRNAs (miRNAs) have emerged as promising biomarkers for cancer detection. This systematic review aims to evaluate the diagnostic performance of circulating miRNAs in detecting colorectal cancer (CRC). A literature search was conducted in PubMed and Scopus. Studies that report sensitivity, specificity, or area under the curve (AUC) for CRC detection by miRNA were included. The miRNA miR-21 was the most frequently studied biomarker, with a varying range of AUC from 0.55 to 0.973 attributed to differences in study populations and methodologies. The miRNAs miR-210 and miR-1246 showed potential diagnostic capacity with miR-1246 achieving an AUC of 0.924, 100% sensitivity, and 80% specificity. The miRNA panels offer improved diagnostic performance compared to individual miRNA. The best performing panel for CRC patients below 50 is miR-211 + miR-25 + TGF-β1 with AUC 0.99 and 100 specificity and 97 sensitivity. Circulating miRNAs hold significant promise as non-invasive biomarkers for CRC screening. However, the variability in diagnostic performance highlights the need for a standardized method and robust validation studies. Future research should focus on large-scale, ethnically diverse cohorts to establish clinically relevant miRNA biomarkers for CRC, particularly in younger populations.
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Affiliation(s)
- Adhari AlZaabi
- Department of Human and Clinical Anatomy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Asem Shalaby
- Department of Pathology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman;
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El-Korany WA, Zahran WE, Alm El-Din MA, Al-Shenawy HA, Soliman AF. Rs12039395 Variant Influences the Expression of hsa-miR-181a-5p and PTEN Toward Colorectal Cancer Risk. Dig Dis Sci 2024; 69:3318-3332. [PMID: 38940971 DOI: 10.1007/s10620-024-08517-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 05/31/2024] [Indexed: 06/29/2024]
Abstract
BACKGROUND Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes could alter miRNA expression levels or processing and, thus, may contribute to colorectal cancer (CRC) development. Therefore, this study aimed to examine whether the MIR181A1 genomic sequence possesses SNPs that can affect the expression of hsa-miR-181a-5p and, subsequently, impact its targets and associate with CRC risk. METHODS The NCBI dbSNP database was searched for possible SNPs associated with MIR181A1. One SNP with a minor allele frequency > 5%, rs12039395 G > T was identified. In silico analyses determined the effect of the SNP on the secondary structure of the miRNA and predicted the hsa-miR-181a-5p target genes. The SNP was genotyped using allelic discrimination assay, the relative hsa-miR-181a-5p expression level was determined using quantitative real-time PCR, and immunohistochemical staining was used to detect target genes in 192 paraffin-embedded specimens collected from 160 CRC patients and 32 healthy subjects. RESULTS The rs6505162 SNP conferred protection against CRC, and the G-allele presence provides may provide accessibility for the transcriptional machinery. Hsa-miR-181a-5p was significantly over-expressed in the CRC group compared to controls and in samples carrying the G-allele compared to those with T-allele. PTEN, identified as the only hsa-miR-181a-5p target implicated in CRC, was significantly diminished in the CRC group compared to controls and showed an inverse relationship with hsa-miR-181a-5p expression level as well as negatively associated with the G-allele presence in CRC. CONCLUSION This study highlights that rs12039395 G > T may protect against CRC by influencing the expression of hsa-mir-181a-5p and its target gene, PTEN.
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Affiliation(s)
- Wael A El-Korany
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Walid E Zahran
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Mohamed A Alm El-Din
- Clinical Oncology Department, Faculty of Medicine, Tanta University, Gharbia, Egypt
| | - Hanan A Al-Shenawy
- Pathology Department, Faculty of Medicine, Tanta University, Gharbia, Egypt
| | - Ahmed F Soliman
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
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Rac M. Synthesis and Regulation of miRNA, Its Role in Oncogenesis, and Its Association with Colorectal Cancer Progression, Diagnosis, and Prognosis. Diagnostics (Basel) 2024; 14:1450. [PMID: 39001340 PMCID: PMC11241650 DOI: 10.3390/diagnostics14131450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 06/27/2024] [Accepted: 07/05/2024] [Indexed: 07/16/2024] Open
Abstract
The dysfunction of several types of regulators, including miRNAs, has recently attracted scientific attention for their role in cancer-associated changes in gene expression. MiRNAs are small RNAs of ~22 nt in length that do not encode protein information but play an important role in post-transcriptional mRNA regulation. Studies have shown that miRNAs are involved in tumour progression, including cell proliferation, cell cycle, apoptosis, and tumour angiogenesis and invasion, and play a complex and important role in the regulation of tumourigenesis. The detection of selected miRNAs may help in the early detection of cancer cells, and monitoring changes in their expression profile may serve as a prognostic factor in the course of the disease or its treatment. MiRNAs may serve as diagnostic and prognostic biomarkers, as well as potential therapeutic targets for colorectal cancer. In recent years, there has been increasing evidence for an epigenetic interaction between DNA methylation and miRNA expression in tumours. This article provides an overview of selected miRNAs, which are more frequently expressed in colorectal cancer cells, suggesting an oncogenic nature.
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Affiliation(s)
- Monika Rac
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Al. Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland
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Das R, Mehta DK, Gupta N. Understanding the Potential of mRNA as Biomarker to Revolutionize Diagnosis of Colorectal Cancer. Drug Res (Stuttg) 2024; 74:102-112. [PMID: 38350633 DOI: 10.1055/a-2244-6572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/15/2024]
Abstract
MicroRNA as potential biomarker for early diagnosis, differentiating various stages, interpreting the success of postoperative curative surgery and predicting early relapse of Colorectal cancer.In the realm of medical research, the quest to find effective biomarkers for various diseases has always been a top priority. Colorectal cancer (CRC), one of the leading causes of cancer-related deaths worldwide, is no exception. The emergence of microRNA (mRNA) as a potential biomarker for CRC has sparked immense interest among scientists and clinicians alike. mRNA, a molecule responsible for translating genetic information into functional proteins, presents a promising avenue for early detection and personalized treatment of this deadly disease. By analyzing the specific patterns and levels of mRNA expression in CRC cells, researchers have the ability to identify signatures that can aid in accurate diagnosis, predict patient prognosis, and even guide targeted therapies. This breakthrough in molecular biology not only enhances our understanding of CRC but also holds the potential to revolutionize the field of cancer diagnostics and treatment. In this article, we will delve deeper into the potential of mRNA as a biomarker for CRC, exploring its benefits and challenges in the field of cancer research.
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Affiliation(s)
- Rina Das
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India
| | - Dinesh Kumar Mehta
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India
| | - Nidhi Gupta
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India
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Yu L, Zeng X, Hu X, Wen Q, Chen P. Advances and challenges in clinical applications of tumor cell-derived extracellular vesicles. Colloids Surf B Biointerfaces 2024; 234:113704. [PMID: 38113751 DOI: 10.1016/j.colsurfb.2023.113704] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 12/05/2023] [Accepted: 12/07/2023] [Indexed: 12/21/2023]
Abstract
Extracellular vesicles (EVs) are a class of substances that feature vesicle-like structures. Initially deemed to be "biological waste", recent studies have highlighted the crucial role of EVs in mediating information communication between cells by transporting bioactive components. Specifically, tumor cell-derived extracellular vesicles (TEVs) contain components that can be utilized for disease diagnosis and as vaccines to activate the immune system. Moreover, since TEVs have a phospholipid bilayer shell and can transport exogenous substances, they are being increasingly explored as drug delivery vehicles in anti-tumor therapy. TEVs have proven highly compatible with their corresponding tumor cells, allowing for efficient drug delivery and exerting killing effects on tumor cells through various mechanisms such as domino effects, lysosomal pathways, and inhibition of drug efflux from tumor tissues. Despite these promising developments, challenges remain in the clinical applications of EVs derived from tumor cells. This paper outlines the current advances and limitations in this field, highlighting the potential of TEVs as a powerful tool for combating cancer.
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Affiliation(s)
- Li Yu
- Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Department of Oncology, Jiangsu Cancer Hospital, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu 210009, China
| | - Xiaonan Zeng
- Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
| | - Xiao Hu
- Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Department of Oncology, the Second Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China
| | - Qinglian Wen
- Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
| | - Ping Chen
- Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
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Ravichandran SN, Kumar MM, Das A, Banerjee A, Veronica S, Sun-Zhang A, Zhang H, Anbalagan M, Sun XF, Pathak S. An Updated Review on Molecular Biomarkers in Diagnosis and Therapy of Colorectal Cancer. Curr Cancer Drug Targets 2024; 24:595-611. [PMID: 38031267 DOI: 10.2174/0115680096270555231113074003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 09/08/2023] [Accepted: 09/21/2023] [Indexed: 12/01/2023]
Abstract
Colorectal cancer is one of the most common cancer types worldwide. Since colorectal cancer takes time to develop, its incidence and mortality can be treated effectively if it is detected in its early stages. As a result, non-invasive or invasive biomarkers play an essential role in the early diagnosis of colorectal cancer. Many experimental studies have been carried out to assess genetic, epigenetic, or protein markers in feces, serum, and tissue. It may be possible to find biomarkers that will help with the diagnosis of colorectal cancer by identifying the genes, RNAs, and/or proteins indicative of cancer growth. Recent advancements in the molecular subtypes of colorectal cancer, DNA methylation, microRNAs, long noncoding RNAs, exosomes, and their involvement in colorectal cancer have led to the discovery of novel biomarkers. In small-scale investigations, most biomarkers appear promising. However, large-scale clinical trials are required to validate their effectiveness before routine clinical implementation. Hence, this review focuses on small-scale investigations and results of big data analysis that may provide an overview of the biomarkers for the diagnosis, therapy, and prognosis of colorectal cancer.
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Affiliation(s)
- Shruthi Nagainallur Ravichandran
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Chennai, Tamil Nadu, 603103, India
| | - Makalakshmi Murali Kumar
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Chennai, Tamil Nadu, 603103, India
| | - Alakesh Das
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Chennai, Tamil Nadu, 603103, India
| | - Antara Banerjee
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Chennai, Tamil Nadu, 603103, India
| | - Suhanya Veronica
- Department of Medical Microbiology and NanoBiomedical Engineering, Medical University of Białystok, ul. Świerkowa, s20 B15-328, Białystok, Poland
| | - Alexander Sun-Zhang
- Department of Oncology- Pathology, BioClinicum, Karolinska Institutet, Stockholm, Sweden
| | - Hong Zhang
- School of Medicine, Department of Medical Sciences, Örebro University, Fakultetsgatan 1, 701 82 Örebro, Sweden
| | - Muralidharan Anbalagan
- School of Medicine, Tulane University School of Medicine, Tulane University, 1430 Tulane Ave, New Orleans, LA70112, United States
| | - Xiao-Feng Sun
- Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University, 58183, Linköping, Sweden
| | - Surajit Pathak
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Chennai, Tamil Nadu, 603103, India
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13
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Sado AI, Batool W, Ahmed A, Zafar S, Patel SK, Mohan A, Zia U, Aminpoor H, Kumar V, Tejwaney U. Role of microRNA in colorectal carcinoma (CRC): a narrative review. Ann Med Surg (Lond) 2024; 86:308-318. [PMID: 38222721 PMCID: PMC10783342 DOI: 10.1097/ms9.0000000000001494] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 11/01/2023] [Indexed: 01/16/2024] Open
Abstract
MicroRNAs (miRNAs) are short non-coding RNAs that play a critical role in regulating gene expression by binding to target messenger RNAs (mRNAs). They were first discovered around 8 years after the identification of the first miRNA in 1993, and since then, there has been a significant increase in miRNA-related research and discoveries. MiRNAs have been implicated in various biological processes, including cancer, particularly in colorectal cancer (CRC). In CRC, miRNAs act as either oncogenes or tumor suppressors, influencing essential cellular functions such as cell proliferation, apoptosis, angiogenesis, and metastasis. The dysregulation of miRNAs in CRC can arise from different factors, leading to abnormal expression levels of their target mRNAs and subsequently affecting protein production. Consequently, miRNAs may directly target oncogenes or tumor suppressor genes, thereby contributing to cancer initiation and progression. Notably, tumors often exhibit reduced expression of mature miRNAs. In CRC research, miRNAs offer potential as diagnostic biomarkers and therapeutic targets. Specific miRNA profiles could serve as non-invasive tools for early CRC detection and risk assessment. Additionally, miRNA-based therapies present a promising approach for targeted cancer treatment by modulating miRNA expression. However, challenges related to delivery systems and long-term safety must be addressed to fully harness their therapeutic potential.
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Affiliation(s)
| | | | | | | | | | | | - Umar Zia
- Khyber Medical University, Peshawar, Pakistan
| | | | - Vikash Kumar
- The Brooklyn Hospital Center, Brooklyn, New York
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14
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Jassi C, Kuo WW, Chang YC, Wang TF, Li CC, Ho TJ, Hsieh DJY, Kuo CH, Chen MC, Huang CY. Aloin and CPT-11 combination activates miRNA-133b and downregulates IGF1R- PI3K/AKT/mTOR and MEK/ERK pathways to inhibit colorectal cancer progression. Biomed Pharmacother 2023; 169:115911. [PMID: 38000359 DOI: 10.1016/j.biopha.2023.115911] [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: 07/02/2023] [Revised: 11/12/2023] [Accepted: 11/20/2023] [Indexed: 11/26/2023] Open
Abstract
CPT-11 is one of the drugs employed in colorectal cancer treatment and has faced challenges in the form of resistance. The insulin-like growth factor 1 receptor is a tyrosine kinase receptor that mediates cancer cell survival and drug resistance. It is frequently overexpressed in colorectal cancer and has previously been identified as a microRNA target. MicroRNAs are non-coding RNA molecules that regulate gene function by suppressing messenger RNA translation. Studies have demonstrated that natural compounds can regulate microRNA function and their target genes. Therefore, combining natural compounds with existing cancer drugs can enhance the therapeutic efficacy. We investigated a natural compound, Aloin, for the potential sensitization of colorectal cancer to CPT-11. We used western blot, MTT cell viability assay, flow cytometry, and microRNA/gene knockdown and overexpression experiments, as well as an in vivo mouse model. Our investigation revealed that combining Aloin with CPT-11 exerts an enhanced anti-tumor effect in colorectal cancer. This combination reduced cell viability and induced apoptosis, both in vivo and in vitro. Furthermore, this combination upregulated miRNA-133b, while downregulating the IGF1R and its downstream MEK/ERK, and PI3K/AKT/mTOR pathways. Our findings suggests that CPT-11 and Aloin are potential combination treatment partners against colorectal cancer. MicroRNA-133b may serve as a co-therapeutic target with IGF1R against colorectal cancer, which might overcome the existing treatment limitations.
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Affiliation(s)
- Chikondi Jassi
- Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
| | - Wei-Wen Kuo
- Department of Biological Science and Technology, China Medical University, Taichung, Taiwan
| | - Yu-Chun Chang
- Department of Biological Science and Technology, China Medical University, Taichung, Taiwan
| | - Tso-Fu Wang
- Department of Hematology and Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; School of Medicine Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien 97004, Taiwan
| | - Chi-Cheng Li
- School of Medicine Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien 97004, Taiwan; Center of Stem Cell & Precision Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Tsung-Jung Ho
- Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan; Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan
| | - Dennis Jine-Yuan Hsieh
- School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan; Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan
| | - Chia-Hua Kuo
- Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan; Department of Kinesiology and Health Science, College of William and Mary, Williamsburg, VA, USA
| | - Ming-Cheng Chen
- Department of Surgery, Division of Colorectal Surgery, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chih-Yang Huang
- Cardiovascular and Mitochondria related diseases research center, Hualien Tzu Chi Hospital, Hualien 970, Taiwan; Graduate Institute of Biomedicine, China Medical University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung 413, Taiwan; Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien 970, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan.
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15
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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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16
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Franz C, Jötten L, Wührl M, Hartmann S, Klupp F, Schmidt T, Schneider M. Protective effect of miR-18a in resected liver metastases of colorectal cancer and FOLFOX treatment. Cancer Rep (Hoboken) 2023; 6:e1899. [PMID: 37698257 PMCID: PMC10728504 DOI: 10.1002/cnr2.1899] [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: 04/27/2023] [Revised: 07/22/2023] [Accepted: 08/27/2023] [Indexed: 09/13/2023] Open
Abstract
BACKGROUND Colorectal cancer ranks second in terms of cancer associated deaths worldwide, whereas miRNA play a pivotal role in the etiology of cancer and its metastases. AIMS Studying the expression and cellular function of miR-18a in metastatic colorectal cancer and association to progression-free survival. METHODS AND RESULTS Colorectal liver metastases (N = 123) and primary colorectal cancer (N = 27) where analyzed by RT-PCR and correlated with clinical follow up data. Invasion and migration assays were performed with the liver metastatic cell line LIM2099 after miR-18a knockdown. Cell viability under FOLFOX treatment and knockdown was measured. We found that the expression of miR-18a was increased 4.38-fold in liver metastases and 3.86-fold in colorectal tumor tissue compared to healthy liver tissue and colorectal mucosa, respectively (p ≤ .001). Patients with a high miR-18a expression in liver metastases had a progression-free survival (PFS) of 13.6 months versus 8.9 months in patients with low expression (N = 123; p = .024). In vitro migration of LIM2099 cells was reduced after miR-18a knockdown and cell viability was significantly increased after miR-18a knockdown and treatment with folinic acid or oxaliplatin. Subgroup analysis of PFS revealed significant benefits for patients with high miR-18a expression receiving 5-FU, folinic acid or oxaliplatin. CONCLUSIONS High expression of miR-18a in colorectal liver metastases might have a protective effect after resection of metastases and FOLFOX treatment regarding PFS.
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Affiliation(s)
- Clemens Franz
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Laila Jötten
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Michael Wührl
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Sibylle Hartmann
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Fee Klupp
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Thomas Schmidt
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Martin Schneider
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
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17
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Ghodasara A, Raza A, Wolfram J, Salomon C, Popat A. Clinical Translation of Extracellular Vesicles. Adv Healthc Mater 2023; 12:e2301010. [PMID: 37421185 DOI: 10.1002/adhm.202301010] [Citation(s) in RCA: 54] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 06/03/2023] [Indexed: 07/10/2023]
Abstract
Extracellular vesicles (EVs) occur in a variety of bodily fluids and have gained recent attraction as natural materials due to their bioactive surfaces, internal cargo, and role in intercellular communication. EVs contain various biomolecules, including surface and cytoplasmic proteins; and nucleic acids that are often representative of the originating cells. EVs can transfer content to other cells, a process that is thought to be important for several biological processes, including immune responses, oncogenesis, and angiogenesis. An increased understanding of the underlying mechanisms of EV biogenesis, composition, and function has led to an exponential increase in preclinical and clinical assessment of EVs for biomedical applications, such as diagnostics and drug delivery. Bacterium-derived EV vaccines have been in clinical use for decades and a few EV-based diagnostic assays regulated under Clinical Laboratory Improvement Amendments have been approved for use in single laboratories. Though, EV-based products are yet to receive widespread clinical approval from national regulatory agencies such as the United States Food and Drug Administration (USFDA) and European Medicine Agency (EMA), many are in late-stage clinical trials. This perspective sheds light on the unique characteristics of EVs, highlighting current clinical trends, emerging applications, challenges and future perspectives of EVs in clinical use.
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Affiliation(s)
- Aayushi Ghodasara
- School of Pharmacy, The University of Queensland, Brisbane, QLD, 4102, Australia
- Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group, The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4029, Australia
| | - Aun Raza
- School of Pharmacy, The University of Queensland, Brisbane, QLD, 4102, Australia
| | - Joy Wolfram
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, 4072, Australia
- The School of Chemical Engineering, The University of Queensland, Brisbane, QLD, 4072, Australia
- Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, 77030, USA
| | - Carlos Salomon
- Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group, The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4029, Australia
- Department of Research, Postgraduate and Further Education (DIPEC), Falcuty of Health Sciences, University of Alba, Santiago, 8320000, Chile
| | - Amirali Popat
- School of Pharmacy, The University of Queensland, Brisbane, QLD, 4102, Australia
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18
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Ranković B, Hauptman N. Circulating microRNA Panels for Detection of Liver Cancers and Liver-Metastasizing Primary Cancers. Int J Mol Sci 2023; 24:15451. [PMID: 37895131 PMCID: PMC10607808 DOI: 10.3390/ijms242015451] [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: 09/29/2023] [Revised: 10/14/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
Malignant liver tumors, including primary malignant liver tumors and liver metastases, are among the most frequent malignancies worldwide. The disease carries a poor prognosis and poor overall survival, particularly in cases involving liver metastases. Consequently, the early detection and precise differentiation of malignant liver tumors are of paramount importance for making informed decisions regarding patient treatment. Significant research efforts are currently directed towards the development of diagnostic tools for different types of cancer using minimally invasive techniques. A prominent area of focus within this research is the evaluation of circulating microRNA, for which dysregulated expression is well documented in different cancers. Combining microRNAs in panels using serum or plasma samples derived from blood holds great promise for better sensitivity and specificity for detection of certain types of cancer.
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Affiliation(s)
| | - Nina Hauptman
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia;
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19
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Li J, Shen J, Zhao Y, Du F, Li M, Wu X, Chen Y, Wang S, Xiao Z, Wu Z. Role of miR‑181a‑5p in cancer (Review). Int J Oncol 2023; 63:108. [PMID: 37539738 PMCID: PMC10552769 DOI: 10.3892/ijo.2023.5556] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 07/13/2023] [Indexed: 08/05/2023] Open
Abstract
MicroRNAs (miRNAs) are non‑coding RNAs (ncRNAs) that can post‑transcriptionally suppress targeted genes. Dysregulated miRNAs are associated with a variety of diseases. MiR‑181a‑5p is a conserved miRNA with the ability to regulate pathological processes, such as angiogenesis, inflammatory response and obesity. Numerous studies have demonstrated that miR‑181a‑5p exerts regulatory influence on cancer development and progression, acting as an oncomiR or tumor inhibitor in various cancer types by impacting multiple hallmarks of tumor. Generally, miR‑181a‑5p binds to target RNA sequences with partial complementarity, resulting in suppression of the targeted genes of miR‑181a‑5p. However, the precise role of miR‑181a‑5p in cancer remains incompletely understood. The present review aims to provide a comprehensive summary of recent research on miR‑181a‑5p, focusing on its involvement in different types of cancer and its potential as a diagnostic and prognostic biomarker, as well as its function in chemoresistance.
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Affiliation(s)
- Junxin Li
- Department of Pharmacy, Affiliated Hospital of Southwest Medical University
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University
- South Sichuan Institute of Translational Medicine
- Laboratory of Personalised Cell Therapy and Cell Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Jing Shen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University
- South Sichuan Institute of Translational Medicine
- Laboratory of Personalised Cell Therapy and Cell Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Yueshui Zhao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University
- South Sichuan Institute of Translational Medicine
- Laboratory of Personalised Cell Therapy and Cell Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Fukuan Du
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University
- South Sichuan Institute of Translational Medicine
- Laboratory of Personalised Cell Therapy and Cell Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Mingxing Li
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University
- South Sichuan Institute of Translational Medicine
- Laboratory of Personalised Cell Therapy and Cell Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Xu Wu
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University
- South Sichuan Institute of Translational Medicine
- Laboratory of Personalised Cell Therapy and Cell Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Yu Chen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University
- South Sichuan Institute of Translational Medicine
- Laboratory of Personalised Cell Therapy and Cell Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Shurong Wang
- Department of Pharmacy, Affiliated Hospital of Southwest Medical University
| | - Zhangang Xiao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University
- South Sichuan Institute of Translational Medicine
- Laboratory of Personalised Cell Therapy and Cell Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Zhigui Wu
- Department of Pharmacy, Affiliated Hospital of Southwest Medical University
- South Sichuan Institute of Translational Medicine
- Laboratory of Personalised Cell Therapy and Cell Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
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20
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Ebrahimi A, Derakhshan SM, Ghavi D, Foruzandeh Z, Hashemi S. The role of mir-151a-5p in tumorigenesis; A systematic review. Pathol Res Pract 2023; 249:154576. [PMID: 37562284 DOI: 10.1016/j.prp.2023.154576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 05/24/2023] [Accepted: 05/25/2023] [Indexed: 08/12/2023]
Abstract
BACKGROUND Highly supported microRNAs (miRNAs) are key players in cancer development. Each of these miRNAs may act as an oncomir, a tumor-suppressor, or both in various cancers. Mir-151a-5p is believed to be one of these miRNAs with diverse roles. We have conducted this systematic review to clarify the role of mir-151a-5p in formation of various cancers. METHODS AND MATERIALS We searched for existing articles in PubMed, Web of Science, Cochrane, Scopus, and RNAcentral databases up to November 2022. A total of 23 articles were qualified and included in the present systematic review. This review is registered on JBI at https://jbi.global/systematic-review-register. Expression levels, diagnostic and prognostic values, biological processes, and targeted downstream genes are included. RESULTS Assembled data indicate the expression levels of mir-151a-5p vary from down- to up-regulated based on the type of the cancer. Its functional role depends on the genetic profile of cancerous tissue. Results mostly point to the oncogenic role of this miRNA in Pituitary adenomas, Acute Myeloid Leukemia (AML), Endometrial, Lung, Barrett's carcinogenesis, Colorectal, Myelodysplastic syndromes, Hepatocellular carcinoma and Breast cancers, as its inhibited targets seem to be controlling several signaling pathways, cell adhesion, and cell cycle. At the same time, tumor-suppressing role has also been observed only in Malignant Pleural Mesothelioma, Central Nerve System (CNS) lymphoma, Chronic Myeloid and Acute Lymphocytic Leukemia. Two types of cancers, prostate and colon, show contradictory results as there are studies supporting both up- and down-regulation in these cancers. Pituitary adenomas, Barrett's carcinogenesis and CNS lymphomas are top cancers diagnosed with mir-151-5p. However, prognostic feature is only applicable to Lung adenocarcinoma. DISCUSSION Based on the present findings and further studies in the future, mir-151a-5p may be used as diagnostic and prognostic biomarkers or even a therapeutic target in cancer studies. DATA AVAILABILITY STATEMENT The articles used in this study can be found with the defined search phrase in mentioned databases. A list of selected articles will be available on reasonable requests.
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Affiliation(s)
- Amir Ebrahimi
- Department of Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Genetics, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Davood Ghavi
- Department of Genetics, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zahra Foruzandeh
- Department of Genetics, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Solmaz Hashemi
- Department of Genetics, Tabriz University of Medical Sciences, Tabriz, Iran
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21
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Guo S, Chen M, Li S, Geng Z, Jin Y, Liu D. Natural Products Treat Colorectal Cancer by Regulating miRNA. Pharmaceuticals (Basel) 2023; 16:1122. [PMID: 37631037 PMCID: PMC10459054 DOI: 10.3390/ph16081122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/26/2023] [Accepted: 08/03/2023] [Indexed: 08/27/2023] Open
Abstract
Diseases are evolving as living standards continue to improve. Cancer is the main cause of death and a major public health problem that seriously threatens human life. Colorectal cancer is one of the top ten most common malignant tumors in China, ranking second after gastric cancer among gastrointestinal malignant tumors, and its incidence rate is increasing dramatically each year due to changes in the dietary habits and lifestyle of the world's population. Although conventional therapies, such as surgery, chemotherapy, and radiotherapy, have profoundly impacted the treatment of colorectal cancer (CRC), drug resistance and toxicity remain substantial challenges. Natural products, such as dietary therapeutic agents, are considered the safest alternative for treating CRC. In addition, there is substantial evidence that natural products can induce apoptosis, inhibit cell cycle arrest, and reduce the invasion and migration of colon cancer cells by targeting and regulating the expression and function of miRNAs. Here, we summarize the recent research findings on the miRNA-regulation-based antitumor mechanisms of various active ingredients in natural products, highlighting how natural products target miRNA regulation in colon cancer prevention and treatment. The application of natural drug delivery systems and predictive disease biomarkers in cancer prevention and treatment is also discussed. Such approaches will contribute to the discovery of new regulatory mechanisms associated with disease pathways and provide a new theoretical basis for developing novel colon cancer drugs and compounds and identifying new therapeutic targets.
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Affiliation(s)
| | | | | | | | - Ye Jin
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (S.G.); (M.C.); (S.L.); (Z.G.)
| | - Da Liu
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (S.G.); (M.C.); (S.L.); (Z.G.)
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22
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Xiong B, Huang Q, Zheng H, Lin S, Xu J. Recent advances microRNAs and metabolic reprogramming in colorectal cancer research. Front Oncol 2023; 13:1165862. [PMID: 37576895 PMCID: PMC10415904 DOI: 10.3389/fonc.2023.1165862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 06/07/2023] [Indexed: 08/15/2023] Open
Abstract
Colorectal cancer (CRC) is a cancer with the highest incidence and mortality. Alteration of gene expression is the main pathophysiological mechanism of CRC, which results in disturbed signaling pathways and cellular metabolic processes. MicroRNAs are involved in almost all pathophysiological processes and are correlative with colorectal cancer metabolism, proliferation, and chemotherapy resistance. Metabolic reprogramming, an important feature of cancer, is strongly correlative with the development and prognosis of cancers, including colorectal cancer. MicroRNAs can target enzymes involved in metabolic processes, thus playing a regulatory role in tumor metabolism. The disorder of the signaling pathway is another characteristic of tumor, which induces the occurrence and proliferation of tumors, and is closely correlative with the prognosis and chemotherapy resistance of tumor patients. MicroRNAs can target the components of the signaling pathways to regulate their transduction. Understanding the function of microRNAs in the occurrence and proliferation of CRC provides novel insights into the optimal treatment strategies, prognosis, and development of diagnosis in CRC. This article reviews the relationship between CRC and microRNA expression and hopes to provide new options for the diagnosis and treatment of CRC.
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Affiliation(s)
- Bin Xiong
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Qiaoyi Huang
- Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Huida Zheng
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Shu Lin
- Centre of Neurological and Metabolic Research, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
- Group of Neuroendocrinology, Garvan Institute of Medical Research, Sydney, NSW, Australia
| | - Jianhua Xu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
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23
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Pelassa S, Raggi F, Rossi C, Bosco MC. MicroRNAs in Juvenile Idiopathic Arthritis: State of the Art and Future Perspectives. BIOLOGY 2023; 12:991. [PMID: 37508421 PMCID: PMC10376583 DOI: 10.3390/biology12070991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 07/03/2023] [Accepted: 07/05/2023] [Indexed: 07/30/2023]
Abstract
Juvenile Idiopathic Arthritis (JIA) represents the most common chronic pediatric arthritis in Western countries and a leading cause of disability in children. Despite recent clinical achievements, patient management is still hindered by a lack of diagnostic/prognostic biomarkers and targeted treatment protocols. MicroRNAs (miRNAs) are short non-coding RNAs playing a key role in gene regulation, and their involvement in many pathologies has been widely reported in the literature. In recent decades, miRNA's contribution to the regulation of the immune system and the pathogenesis of autoimmune diseases has been demonstrated. Furthermore, miRNAs isolated from patients' biological samples are currently under investigation for their potential as novel biomarkers. This review aims to provide an overview of the state of the art on miRNA investigation in JIA. The literature addressing the expression of miRNAs in different types of biological samples isolated from JIA patients was reviewed, focusing in particular on their potential application as diagnostic/prognostic biomarkers. The role of miRNAs in the regulation of immune responses in affected joints will also be discussed along with their potential utility as markers of patients' responses to therapeutic approaches. This information will be of value to investigators in the field of pediatric rheumatology, encouraging further research to increase our knowledge of miRNAs' potential for future clinical applications in JIA.
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Affiliation(s)
- Simone Pelassa
- UOC Rheumatology and Autoinflammatory Diseases, Department of Pediatric Sciences, Istituto Giannina Gaslini, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 16147 Genova, Italy
| | - Federica Raggi
- UOC Rheumatology and Autoinflammatory Diseases, Department of Pediatric Sciences, Istituto Giannina Gaslini, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 16147 Genova, Italy
| | - Chiara Rossi
- UOC Rheumatology and Autoinflammatory Diseases, Department of Pediatric Sciences, Istituto Giannina Gaslini, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 16147 Genova, Italy
| | - Maria Carla Bosco
- UOC Rheumatology and Autoinflammatory Diseases, Department of Pediatric Sciences, Istituto Giannina Gaslini, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 16147 Genova, Italy
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24
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Santos DAR, Gaiteiro C, Santos M, Santos L, Dinis-Ribeiro M, Lima L. MicroRNA Biomarkers as Promising Tools for Early Colorectal Cancer Screening-A Comprehensive Review. Int J Mol Sci 2023; 24:11023. [PMID: 37446201 DOI: 10.3390/ijms241311023] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 06/30/2023] [Accepted: 06/30/2023] [Indexed: 07/15/2023] Open
Abstract
Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide. Early detection of this neoplasia has proven to improve prognosis, resulting in a 90% increase in survival. However, available CRC screening methods have limitations, requiring the development of new tools. MicroRNA biomarkers have emerged as a powerful screening tool, as they are highly expressed in CRC patients and easily detectable in several biological samples. While microRNAs are extensively studied in blood samples, recent interest has now arisen in other samples, such as stool samples, where they can be combined with existing screening methods. Among the microRNAs described in the literature, microRNA-21-5p and microRNA-92a-3p and their cluster have demonstrated high potential for early CRC screening. Furthermore, the combination of multiple microRNAs has shown improved performance in CRC detection compared to individual microRNAs. This review aims to assess the available data in the literature on microRNAs as promising biomarkers for early CRC screening, explore their advantages and disadvantages, and discuss the optimal study characteristics for analyzing these biomarkers.
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Affiliation(s)
- Daniela A R Santos
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal
- School of Health, Polytechnic Institute of Porto, Rua Dr. António Bernardino de Almeida, 400, 4200-072 Porto, Portugal
| | - Cristiana Gaiteiro
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal
| | - Marlene Santos
- School of Health, Polytechnic Institute of Porto, Rua Dr. António Bernardino de Almeida, 400, 4200-072 Porto, Portugal
- Centro de Investigação em Saúde e Ambiente (CISA), Escola Superior de Saúde, Instituto Politécnico do Porto, 4200-072 Porto, Portugal
- Molecular Oncology & Viral Pathology, IPO-Porto Research Center (CI-IPO), Portuguese Institute of Oncology, 4200-072 Porto, Portugal
| | - Lúcio Santos
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal
- Department of Surgical Oncology, Portuguese Institute of Oncology (IPO-Porto), 4200-072 Porto, Portugal
| | - Mário Dinis-Ribeiro
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI-IPOP), Rise@CI-IPOP (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal
- Department of Gastroenterology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal
| | - Luís Lima
- Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal
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25
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Zhang Y, Wang Y, Zhang B, Li P, Zhao Y. Methods and biomarkers for early detection, prediction, and diagnosis of colorectal cancer. Biomed Pharmacother 2023; 163:114786. [PMID: 37119736 DOI: 10.1016/j.biopha.2023.114786] [Citation(s) in RCA: 48] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/17/2023] [Accepted: 04/24/2023] [Indexed: 05/01/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common digestive diseases worldwide. It has steadily ascended to the top three cancers in terms of incidence and mortality. The primary cause is the inability to diagnose it at an early stage. Therefore, early detection and diagnosis are essential for colorectal cancer prevention. Although there are now various methods for CRC early detection, in addition to recent developments in surgical and multimodal therapy, the poor prognosis and late detection of CRC still remain significant. Thus, it is important to investigate novel technologies and biomarkers to improve the sensitization and specification of CRC diagnosis. Here, we present some common methods and biomarkers for early detection and diagnosis of CRC, we hope this review will encourage the adoption of screening programs and the clinical use of these potential molecules as biomarkers for CRC early detection and prognosis.
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Affiliation(s)
- Yue Zhang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Yin Wang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China; Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Maternal and Child Health Care Hospital of Shandong Province affiliated to Qingdao University, Shandong Province, China
| | - Bingqiang Zhang
- Key Laboratory of Cancer and Immune Cells of Qingdao, Qingdao 266021, China
| | - Peifeng Li
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China.
| | - Yi Zhao
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China.
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26
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Pös O, Styk J, Buglyó G, Zeman M, Lukyova L, Bernatova K, Hrckova Turnova E, Rendek T, Csók Á, Repiska V, Nagy B, Szemes T. Cross-Kingdom Interaction of miRNAs and Gut Microbiota with Non-Invasive Diagnostic and Therapeutic Implications in Colorectal Cancer. Int J Mol Sci 2023; 24:10520. [PMID: 37445698 DOI: 10.3390/ijms241310520] [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: 05/17/2023] [Revised: 06/15/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Colorectal cancer (CRC) has one of the highest incidences among all types of malignant diseases, affecting millions of people worldwide. It shows slow progression, making it preventable. However, this is not the case due to shortcomings in its diagnostic and management procedure and a lack of effective non-invasive biomarkers for screening. Here, we discuss CRC-associated microRNAs (miRNAs) and gut microbial species with potential as CRC diagnostic and therapy biomarkers. We provide rich evidence of cross-kingdom miRNA-mediated interactions between the host and gut microbiome. miRNAs have emerged with the ability to shape the composition and dynamics of gut microbiota. Intestinal microbes can uptake miRNAs, which in turn influence microbial growth and provide the ability to regulate the abundance of various microbial species. In the context of CRC, targeting miRNAs could aid in manipulating the balance of the microbiota. Our findings suggest the need for correlation analysis between the composition of the gut microbiome and the miRNA expression profile.
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Affiliation(s)
- Ondrej Pös
- Comenius University Science Park, 841 04 Bratislava, Slovakia
- Geneton Ltd., 841 04 Bratislava, Slovakia
| | - Jakub Styk
- Comenius University Science Park, 841 04 Bratislava, Slovakia
- Geneton Ltd., 841 04 Bratislava, Slovakia
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia
| | - Gergely Buglyó
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
| | - Michal Zeman
- Comenius University Science Park, 841 04 Bratislava, Slovakia
| | - Lydia Lukyova
- Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, 842 05 Bratislava, Slovakia
| | - Kamila Bernatova
- Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, 842 05 Bratislava, Slovakia
| | - Evelina Hrckova Turnova
- Comenius University Science Park, 841 04 Bratislava, Slovakia
- Slovgen Ltd., 841 04 Bratislava, Slovakia
| | - Tomas Rendek
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia
| | - Ádám Csók
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
| | - Vanda Repiska
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia
- Medirex Group Academy, n.p.o., 949 05 Nitra, Slovakia
| | - Bálint Nagy
- Comenius University Science Park, 841 04 Bratislava, Slovakia
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
| | - Tomas Szemes
- Comenius University Science Park, 841 04 Bratislava, Slovakia
- Geneton Ltd., 841 04 Bratislava, Slovakia
- Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, 842 05 Bratislava, Slovakia
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27
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Zhang D, Hua M, Zhang N. LINC01232 promotes lung squamous cell carcinoma progression through modulating miR-181a-5p/SMAD2 axis. Am J Med Sci 2023; 365:386-395. [PMID: 36543302 DOI: 10.1016/j.amjms.2022.12.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 07/21/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND LINC01232 has been implicated in the progression of multiple malignancies. Yet, the function of LINC01232 in the carcinogenesis of lung squamous cell carcinoma (LUSC) remains unclear. This study aims to examine the role LINC01232 plays in LUSC progression. METHODS mRNA and protein levels were assessed using qRT-PCR and western blot, respectively. Cell proliferation was assessed by CCK-8 and colony formation assays. Cell migration and invasion were evaluated by transwell assay. The interactions between LINC01232, miR-181a-5p, and SMAD2 were assessed using luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays. The subcellular distribution of LINC01232 was examined by cytosolic/nuclear fractionation assay RESULTS: LINC01232 was upregulated in both LUSC tissues and cell lines. Knockdown of LINC01232 impaired cell proliferation, migration and invasion capability in H1229 and A549 cells, a phenotype that could be reversed by miR-181a-5p silencing. In addition, LINC01232 silencing reduced levels of N-cadherin, Vimentin, and Snail in H1229 and A549 cells, but increased the level of E-cadherin, which can be abrogated by miR-181a-5p inhibitors. CONCLUSIONS In summary, our study demonstrates that LINC01232 expression increases in LUSC tissues and cell lines and promotes LUSC progression by modulating the miR-181a-5p/SMAD2 signaling, providing new potential drug targets for LUSC treatment.
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Affiliation(s)
- Dongliang Zhang
- Department of Thoracic Surgery, China Coast Guard Hospital of the People's Armed Police Force, Jiaxing, Zhejiang Province, China
| | - Minglei Hua
- Department of Respiratory Medicine, Xincheng Branch of Zaozhuang Municipal Hospital, Zaozhuang, Shandong Province, China
| | - Nan Zhang
- Department of Medical Oncology, China Coast Guard Hospital of the People's Armed Police Force, Jiaxing, Zhejiang Province, China.
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28
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Xie Y, Zhang Y, Liu X, Cao L, Han M, Wang C, Chen J, Zhang X. miR‑151a‑5p promotes the proliferation and metastasis of colorectal carcinoma cells by targeting AGMAT. Oncol Rep 2023; 49:50. [PMID: 36704851 PMCID: PMC9887461 DOI: 10.3892/or.2023.8487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 01/11/2023] [Indexed: 01/22/2023] Open
Abstract
Colorectal carcinoma (CRC) is one of the most common types of digestive cancer. It has been reported that the ectopic expression of microRNAs (miRs) plays a critical role in the occurrence and progression of CRC. In addition, it has also been suggested that miR‑151a‑5p may serve as a useful biomarker for the early detection and treatment of different types of cancer and particularly CRC. However, the specific effects and underlying mechanisms of miR‑151a‑5p in CRC remain elusive. The results of the current study demonstrated that miR‑151a‑5p was upregulated in CRC cell lines and clinical tissues derived from patients with CRC. Functionally, the results showed that miR‑151a‑5p significantly promoted CRC cell proliferation, migration and invasion. Additionally, dual luciferase reporter assays verified that agmatinase (AGMAT) was a direct target of miR‑151a‑5p and it was positively associated with miR‑151a‑5p expression. Mechanistically, miR‑151a‑5p could enhance the epithelial‑mesenchymal transition of CRC cells. Taken together, the results of the current study revealed a novel molecular mechanism indicating that the miR‑151a‑5p/AGMAT axis could serve a crucial role in the regulation of CRC and could therefore be considered as a potential therapeutic strategy for CRC.
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Affiliation(s)
- Yaya Xie
- Department of Gastroenterology, Anhui University of Science and Technology Affiliated Fengxian Hospital, Fengxian, Shanghai 201499, P.R. China
- School of Medical, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China
| | - Yue Zhang
- School of Medical, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China
- Hanzhong Central Hospital of Shaanxi, Hanzhong, Shaanxi 723000, P.R. China
| | - Xianju Liu
- Department of Gastroenterology, Anhui University of Science and Technology Affiliated Fengxian Hospital, Fengxian, Shanghai 201499, P.R. China
- School of Medical, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China
| | - Lijun Cao
- Department of Gastroenterology, Anhui University of Science and Technology Affiliated Fengxian Hospital, Fengxian, Shanghai 201499, P.R. China
- School of Medical, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China
| | - Mengting Han
- School of Medical, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China
| | - Chunmei Wang
- Department of Gastroenterology, Anhui University of Science and Technology Affiliated Fengxian Hospital, Fengxian, Shanghai 201499, P.R. China
| | - Jinlian Chen
- Department of Gastroenterology, Anhui University of Science and Technology Affiliated Fengxian Hospital, Fengxian, Shanghai 201499, P.R. China
| | - Xingxing Zhang
- Department of Gastroenterology, Anhui University of Science and Technology Affiliated Fengxian Hospital, Fengxian, Shanghai 201499, P.R. China
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29
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Rapado-González Ó, López-López R, Suárez-Cunqueiro MM. Liquid biopsy-based microRNA models as potential biomarkers of bowel conditions. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2023; 115:59-63. [PMID: 36454105 DOI: 10.17235/reed.2022.9027/2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
MicroRNAs detected in liquid biopsies have demonstrated to have potential as biomarkers of benign and malignant bowel conditions. Numerous studies have reported on the combination of different microRNAs to improve the diagnostic capabilities in the detection of bowel conditions. This editorial will be reviewing the best scientific evidence available to this date on studies showing microRNA models with sensitivity and specificity values. Also, the current challenges on how to implement microRNAs in the routine clinical practice are exposed.
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Affiliation(s)
- Óscar Rapado-González
- Translational Medical Oncology Group (ONCOMET), Universidad de Santiago de Compostela , Spain
| | - Rafael López-López
- Oncología Médica, Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Spain
| | - María Mercedes Suárez-Cunqueiro
- Surgery and Medical-Surgical Specialties, Medicine and Dentistry School. Complexo Hospitalario Universitario de Santiago de Compostela -SERGAS, Spain
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30
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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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31
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Xia Y, Yu C, Johann Helwig E, Li Y. The Role of Extracellular Vesicles in Colorectal Cancer. Technol Cancer Res Treat 2023; 22:15330338231185008. [PMID: 37418639 PMCID: PMC10331217 DOI: 10.1177/15330338231185008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 04/18/2023] [Accepted: 06/08/2023] [Indexed: 07/09/2023] Open
Abstract
Extracellular vesicles (EVs) are a class of spherical vesicles that are produced by active secretion of cells and encapsulated by phospholipid bilayers. In recent years, numerous studies have shown that EVs play pivotal roles in the regulation of intercellular communication between colorectal cancer (CRC) cells and target cells, and can regulate the proliferation, metastasis, and infiltration of tumor cells by regulating the microenvironment of tumor cells. EVs carry specific molecular substances in source CRC cells and are expected to serve as new molecular markers for the detection of cancers. This review highlights the current state of research and progress of potentially incorporating EVs in the diagnosis and treatment of CRC.
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Affiliation(s)
- Yujian Xia
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China
| | - Chaoran Yu
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Ernest Johann Helwig
- Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Yousheng Li
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
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32
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Pliakou E, Lampropoulou DI, Dovrolis N, Chrysikos D, Filippou D, Papadimitriou C, Vezakis A, Aravantinos G, Gazouli M. Circulating miRNA Expression Profiles and Machine Learning Models in Association with Response to Irinotecan-Based Treatment in Metastatic Colorectal Cancer. Int J Mol Sci 2022; 24:46. [PMID: 36613487 PMCID: PMC9820223 DOI: 10.3390/ijms24010046] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/09/2022] [Accepted: 12/15/2022] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer represents a leading cause of cancer-related morbidity and mortality. Despite improvements, chemotherapy remains the backbone of colorectal cancer treatment. The aim of this study is to investigate the variation of circulating microRNA expression profiles and the response to irinotecan-based treatment in metastatic colorectal cancer and to identify relevant target genes and molecular functions. Serum samples from 95 metastatic colorectal cancer patients were analyzed. The microRNA expression was tested with a NucleoSpin miRNA kit (Machnery-Nagel, Germany), and a machine learning approach was subsequently applied for microRNA profiling. The top 10 upregulated microRNAs in the non-responders group were hsa-miR-181b-5p, hsa-miR-10b-5p, hsa-let-7f-5p, hsa-miR-181a-5p, hsa-miR-181d-5p, hsa-miR-301a-3p, hsa-miR-92a-3p, hsa-miR-155-5p, hsa-miR-30c-5p, and hsa-let-7i-5p. Similarly, the top 10 downregulated microRNAs were hsa-let-7d-5p, hsa-let-7c-5p, hsa-miR-215-5p, hsa-miR-143-3p, hsa-let-7a-5p, hsa-miR-10a-5p, hsa-miR-142-5p, hsa-miR-148a-3p, hsa-miR-122-5p, and hsa-miR-17-5p. The upregulation of microRNAs in the miR-181 family and the downregulation of those in the let-7 family appear to be mostly involved with non-responsiveness to irinotecan-based treatment.
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Affiliation(s)
- Evangelia Pliakou
- Second Department of Medical Oncology, General Oncology Hospital of Kifissia “Agioi Anargiroi”, Nea Kifissia, 14564 Athens, Greece
| | | | - Nikolas Dovrolis
- Laboratory of Biology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Dimosthenis Chrysikos
- 1st Department of Propaedeutic Surgery, Hippoctation Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Dimitrios Filippou
- Department of Anatomy, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Christos Papadimitriou
- Second Department of Surgery, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Antonios Vezakis
- Department of Surgery, Aretaieion University Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Gerasimos Aravantinos
- Second Department of Medical Oncology, General Oncology Hospital of Kifissia “Agioi Anargiroi”, Nea Kifissia, 14564 Athens, Greece
| | - Maria Gazouli
- Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
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33
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Suzuki K, Yamaguchi T, Kohda M, Tanaka M, Takemura H, Wakita M, Tabe Y, Kato S, Nasu M, Hashimoto T, Mine S, Serizawa N, Tomishima K, Nagahara A, Matsuda T, Yamaji T, Tsugane S, Saito Y, Daiko H, Yoshikawa T, Kato K, Okusaka T, Ochiya T, Yamamoto Y, Yotsui S, Yamamoto T, Yamasaki T, Miyata H, Yasui M, Omori T, Ohkawa K, Ikezawa K, Nakabori T, Sugimoto N, Kudo T, Yoshida K, Ohue M, Nishizawa T. Establishment of preanalytical conditions for microRNA profile analysis of clinical plasma samples. PLoS One 2022; 17:e0278927. [PMID: 36516194 PMCID: PMC9750036 DOI: 10.1371/journal.pone.0278927] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 11/23/2022] [Indexed: 12/15/2022] Open
Abstract
The relationship between the expression of microRNAs (miRNAs) in blood and a variety of diseases has been investigated. MiRNA-based liquid biopsy has attracted much attention, and cancer-specific miRNAs have been reported. However, the results of analyses of the expression of these miRNAs vary among studies. The reproduction of results regarding miRNA expression levels could be difficult if there are differences in the data acquisition process. Previous studies have shown that the anticoagulant type used during plasma preparation and sample storage conditions could contribute to differences in measured miRNA levels. Thus, the impact of these preanalytical conditions on comprehensive miRNA expression profiles was examined. First, the miRNA expression profiles of samples obtained from healthy volunteers were analyzed using next-generation sequencing. Based on an analysis of the library concentration, human genome identification rate, ratio of unique sequences and expression profiles, the optimal preanalytical conditions for obtaining highly reproducible miRNA expression profiles were established. The optimal preanalytical conditions were as follows: ethylenediaminetetraacetic acid (EDTA) as the anticoagulant, whole-blood storage at room temperature within 6 hours, and plasma storage at 4°C or -20°C within 30 days. Next, plasma samples were collected from 60 cancer patients (3 facilities × 20 patients/facility), and miRNA expression profiles were analyzed. There were no significant differences in measurements except in the expression of erythrocyte-derived hsa-miR-451a. However, the variation in hsa-miR-451a levels was smaller among facilities than among individuals. This finding suggests that samples obtained from the same facility could show significantly different degrees of hemolysis across individuals. We found that the standardization of anticoagulant use and storage conditions contributed to reducing the variation in sample quality across facilities. The findings from this study could be useful in developing protocols for collecting samples from multiple facilities for cancer screening tests.
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Affiliation(s)
- Kuno Suzuki
- Healthcare Business Department, PFDeNA, Inc., Tokyo, Japan
- * E-mail:
| | | | - Masakazu Kohda
- Healthcare Business Department, PFDeNA, Inc., Tokyo, Japan
| | - Masami Tanaka
- Healthcare Business Department, PFDeNA, Inc., Tokyo, Japan
| | - Hiroyuki Takemura
- Department of Clinical Laboratory, Juntendo University Hospital, Tokyo, Japan
| | - Mitsuru Wakita
- Department of Clinical Laboratory, Juntendo University Hospital, Tokyo, Japan
| | - Yoko Tabe
- Department of Clinical Laboratory, Juntendo University Hospital, Tokyo, Japan
| | - Shunsuke Kato
- Department of Clinical Oncology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Motomi Nasu
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Takashi Hashimoto
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Shinji Mine
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Nobuko Serizawa
- Department of Gastroenterology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Ko Tomishima
- Department of Gastroenterology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Takahisa Matsuda
- Cancer Screening Center, National Cancer Center Hospital, Tokyo, Japan
| | - Taiki Yamaji
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Shoichiro Tsugane
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Yutaka Saito
- Department of Endoscopy, National Cancer Center Hospital, Tokyo, Japan
| | - Hiroyuki Daiko
- Department of Esophageal Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Takaki Yoshikawa
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Ken Kato
- Department of Head and Neck, Esophageal Medical Oncology / Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Takahiro Ochiya
- Laboratory of Integrative Oncology, National Cancer Center Research Institute, Tokyo, Japan
| | - Yusuke Yamamoto
- Laboratory of Integrative Oncology, National Cancer Center Research Institute, Tokyo, Japan
| | - Shoji Yotsui
- Clinical Laboratory, Osaka International Cancer Institute, Osaka, Japan
| | - Takashi Yamamoto
- Clinical Laboratory, Osaka International Cancer Institute, Osaka, Japan
| | - Tomoyuki Yamasaki
- Clinical Laboratory, Osaka International Cancer Institute, Osaka, Japan
| | - Hiroshi Miyata
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Masayoshi Yasui
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Takeshi Omori
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Kazuyoshi Ohkawa
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Kenji Ikezawa
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Tasuku Nakabori
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Naotoshi Sugimoto
- Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Toshihiro Kudo
- Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Keiichi Yoshida
- Next-generation Precision Medicine Research Center, Osaka International Cancer Institute, Osaka, Japan
| | - Masayuki Ohue
- Next-generation Precision Medicine Research Center, Osaka International Cancer Institute, Osaka, Japan
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Multi-Omics Approaches in Colorectal Cancer Screening and Diagnosis, Recent Updates and Future Perspectives. Cancers (Basel) 2022; 14:cancers14225545. [PMID: 36428637 PMCID: PMC9688479 DOI: 10.3390/cancers14225545] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 11/07/2022] [Accepted: 11/09/2022] [Indexed: 11/15/2022] Open
Abstract
Colorectal cancer (CRC) is common Cancer as well as the third leading cause of mortality around the world; its exact molecular mechanism remains elusive. Although CRC risk is significantly correlated with genetic factors, the pathophysiology of CRC is also influenced by external and internal exposures and their interactions with genetic factors. The field of CRC research has recently benefited from significant advances through Omics technologies for screening biomarkers, including genes, transcripts, proteins, metabolites, microbiome, and lipidome unbiasedly. A promising application of omics technologies could enable new biomarkers to be found for the screening and diagnosis of CRC. Single-omics technologies cannot fully understand the molecular mechanisms of CRC. Therefore, this review article aims to summarize the multi-omics studies of Colorectal cancer, including genomics, transcriptomics, proteomics, microbiomics, metabolomics, and lipidomics that may shed new light on the discovery of novel biomarkers. It can contribute to identifying and validating new CRC biomarkers and better understanding colorectal carcinogenesis. Discovering biomarkers through multi-omics technologies could be difficult but valuable for disease genotyping and phenotyping. That can provide a better knowledge of CRC prognosis, diagnosis, and treatments.
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Sur D, Advani S, Braithwaite D. MicroRNA panels as diagnostic biomarkers for colorectal cancer: A systematic review and meta-analysis. Front Med (Lausanne) 2022; 9:915226. [PMID: 36419785 PMCID: PMC9676370 DOI: 10.3389/fmed.2022.915226] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 10/21/2022] [Indexed: 11/09/2022] Open
Abstract
Background Circulating microRNAs (miRNA) have emerged as promising diagnostic biomarkers for several diseases, including cancer. However, the diagnostic accuracy of miRNA panels in colorectal cancer (CRC) remains inconsistent and there is still lack of meta-analyses to determine whether miRNA panels can serve as robust biomarkers for CRC diagnosis. Methods This study performed a systematic review and meta-analysis to evaluate the clinical utility of miRNA panels as potential biomarkers for the diagnosis of CRC. The investigation systematically searched PubMed, Medline, Web of Science, Cochrane Library, and Google Scholar (21-year span, between 2000 and 2021) to retrieve articles reporting the diagnostic role of miRNA panels in detecting CRC. Diagnostic meta-analysis of miRNA panels used diverse evaluation indicators, including sensitivity, specificity, Positive Likelihood Ratio (PLR), Negative Likelihood Ratio (NLR), Diagnostic Odds Ratio (DOR), and the area under the curve (AUC) values. Results Among the 313 articles identified, 20 studies met the inclusion criteria. The pooled estimates of miRNA panels for the diagnosis of CRC were 0.85 (95% CI: 0.84-0.86), 0.79 (95% CI: 0.78-0.80), 4.06 (95% CI: 3.89-4.23), 0.20 (95% CI: 0.19-0.20), 22.50 (95% CI: 20.81-24.32) for sensitivity, specificity, PLR, NLR, and DOR, respectively. Moreover, the summary receiver operating characteristics (SROC) curve revealed an AUC value of 0.915 (95% CI: 0.914-0.916), suggesting an outstanding diagnostic accuracy for overall miRNA panels. Subgroup and meta-regression analyses demonstrated that miRNA panels have the highest diagnostic accuracy within serum samples, rather than in other sample-types - with a sensitivity, specificity, PLR, NLR, DOR, and AUC of 0.87, 0.86, 7.33, 0.13, 55.29, and 0.943, respectively. Sensitivity analysis revealed that DOR values did not differ markedly, which indicates that the meta-analysis had strong reliability. Furthermore, this study demonstrated no proof of publication bias for DOR values analyzed using Egger's regression test (P > 0.05) and funnel plot. Interestingly, miR-15b, miR-21 and miR-31 presented the best diagnostic accuracy values for CRC with sensitivity, specificity, PLR, NLR, DOR, and AUC values of 0.95, 0.94, 17.19, 0.05, 324.81, and 0.948, respectively. Conclusion This study's findings indicated that miRNA panels, particularly serum-derived miRNA panels, can serve as powerful and promising biomarkers for early CRC screening. Systematic review registration [www.crd.york.ac.uk/prospero], identifier [CRD42021268172].
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Affiliation(s)
- Daniel Sur
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuţă” Cluj-Napoca, Cluj-Napoca, Romania,11th Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Haţieganu”, Cluj-Napoca, Romania,*Correspondence: Daniel Sur,
| | - Shailesh Advani
- Department of Oncology, Georgetown University School of Medicine, Washington, DC, United States,Terasaki Institute of Biomedical Innovation, Los Angeles, CA, United States
| | - Dejana Braithwaite
- Department of Epidemiology, University of Florida College of Public Health and Health Professions, Gainesville, FL, United States,University of Florida Health Cancer Center, Gainesville, FL, United States,Department of Aging and Geriatric Research, University of Florida College of Medicine, Gainesville, FL, United States
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Ebrahimi N, Faghihkhorasani F, Fakhr SS, Moghaddam PR, Yazdani E, Kheradmand Z, Rezaei-Tazangi F, Adelian S, Mobarak H, Hamblin MR, Aref AR. Tumor-derived exosomal non-coding RNAs as diagnostic biomarkers in cancer. Cell Mol Life Sci 2022; 79:572. [PMID: 36308630 PMCID: PMC11802992 DOI: 10.1007/s00018-022-04552-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 09/02/2022] [Accepted: 09/04/2022] [Indexed: 12/24/2022]
Abstract
Almost all clinical oncologists agree that the discovery of reliable, accessible, and non-invasive biomarkers is necessary to decrease cancer mortality. It is possible to employ reliable biomarkers to diagnose cancer in the early stages, predict the patient prognosis, follow up the response to treatment, and estimate the risk of disease recurrence with high sensitivity and specificity. Extracellular vesicles (EVs), especially exosomes, have been the focus of translational research to develop such biomarkers over the past decade. The abundance and distribution of exosomes in bodily fluids, including serum, saliva, and urine, as well as their ability to transport various biomolecules (nucleic acids, proteins, and lipids) derived from their parent cells, make exosomes reliable, accessible, and potent biomarkers for diagnosis and follow-up of solid and hematopoietic tumors. In addition, exosomes play a vital role in various cellular processes, including tumor progression, by participating in intercellular communication. Although these advantages underline the high potential of tumor-derived exosomes as diagnostic biomarkers, the lack of standardized effective methods for their isolation, identification, and precise characterization makes their application challenging in clinical settings. We discuss the importance of non-coding RNAs (ncRNAs) in cellular processes, and the role of tumor-derived exosomes containing ncRNAs as potential biomarkers in several types of cancer. In addition, the advantages and challenges of these studies for translation into clinical applications are covered.
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Affiliation(s)
- Nasim Ebrahimi
- Genetics Division, Department of Cell and Molecular Biology and Microbiology, Faculty of Science and Technology, University of Isfahan, Isfahan, Iran
| | | | - Siavash Seifollahy Fakhr
- Division of Biotechnology, Faculty of Applied Ecology, Agricultural Sciences and Biotechnology, Campus, Hamar, Norway
| | - Parichehr Roozbahani Moghaddam
- Department of Molecular Genetics, Faculty of Science, Tonekabon Branch, Islamic Azad University, Tehran, Mazandaran, Iran
| | - Elnaz Yazdani
- Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Iran
- Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
| | - Zahra Kheradmand
- Department of Agriculture, Islamic Azad University Maragheh Branch, Maragheh, Iran
| | - Fatemeh Rezaei-Tazangi
- Department of Anatomy, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Samaneh Adelian
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Halimeh Mobarak
- Clinical Pathologist, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028, South Africa.
| | - Amir Reza Aref
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.
- Translational Medicine Group, Xsphera Biosciences, 6 Tide Street, Boston, MA, 02210, USA.
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Assessment of miR-103a-3p in leukocytes-No diagnostic benefit in combination with the blood-based biomarkers mesothelin and calretinin for malignant pleural mesothelioma diagnosis. PLoS One 2022; 17:e0275936. [PMID: 36240245 PMCID: PMC9565669 DOI: 10.1371/journal.pone.0275936] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 09/26/2022] [Indexed: 11/19/2022] Open
Abstract
Malignant pleural mesothelioma (MPM) is a cancer associated with asbestos exposure and its diagnosis is challenging due to the moderate sensitivities of the available methods. In this regard, miR-103a-3p was considered to increase the sensitivity of established biomarkers to detect MPM. Its behavior and diagnostic value in the Mexican population has not been previously evaluated. In 108 confirmed MPM cases and 218 controls, almost all formerly exposed to asbestos, we quantified miR-103-3a-3p levels in leukocytes using quantitative Real-Time PCR, together with mesothelin and calretinin measured in plasma by ELISA. Sensitivity and specificity of miR-103-3a-3p alone and in combination with mesothelin and calretinin were determined. Bivariate analysis was performed using Mann-Whitney U test and Spearman correlation. Non-conditional logistic regression models were used to calculate the area under curve (AUC), sensitivity, and specificity for the combination of biomarkers. Mesothelin and calretinin levels were higher among cases, remaining as well among males and participants ≤60 years old (only mesothelin). Significant differences for miR-103a-3p were observed between male cases and controls, whereas significant differences between cases and controls for mesothelin and calretinin were observed in men and women. At 95.5% specificity the individual sensitivity of miR-103a-3p was 4.4% in men, whereas the sensitivity of mesothelin and calretinin was 72.2% and 80.9%, respectively. Positive correlations for miR-103a-3p were observed with age, environmental asbestos exposure, years with diabetes mellitus, and glucose levels, while negative correlations were observed with years of occupational asbestos exposure, creatinine, erythrocytes, direct bilirubin, and leukocytes. The addition of miR-103a-3p to mesothelin and calretinin did not increase the diagnostic performance for MPM diagnosis. However, miR-103a-3p levels were correlated with several characteristics in the Mexican population.
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Liang C, Yang JB, Lin XY, Xie BL, Xu YX, Lin S, Xu TW. Recent advances in the diagnostic and therapeutic roles of microRNAs in colorectal cancer progression and metastasis. Front Oncol 2022; 12:911856. [PMID: 36313731 PMCID: PMC9607901 DOI: 10.3389/fonc.2022.911856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 09/26/2022] [Indexed: 11/13/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common malignancy in the world and one of the leading causes of cancer death; its incidence is still increasing in most countries. The early diagnostic accuracy of CRC is low, and the metastasis rate is high, resulting in a low survival rate of advanced patients. MicroRNAs (miRNAs) are a small class of noncoding RNAs that can inhibit mRNA translation and trigger mRNA degradation, and can affect a variety of cellular and molecular targets. Numerous studies have shown that miRNAs are related to tumour progression, immune system activity, anticancer drug resistance, and the tumour microenvironment. Dysregulation of miRNAs occurs in a variety of malignancies, including CRC. In this review, we summarize the recent research progress of miRNAs, their roles in tumour progression and metastasis, and their clinical value as potential biomarkers or therapeutic targets for CRC. Furthermore, we combined the roles of miRNAs in tumorigenesis and development with the therapeutic strategies of CRC patients, which will provide new ideas for the diagnosis and treatment of CRC.
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Affiliation(s)
- Chen Liang
- Department of Digestive Tumours, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Jing-Bo Yang
- Department of Digestive Tumours, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Xin-Yi Lin
- Department of Digestive Tumours, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Bi-Lan Xie
- Department of Digestive Tumours, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Yun-Xian Xu
- Department of Digestive Tumours, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Shu Lin
- Centre of Neurological and Metabolic Research, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
- Group of Neuroendocrinology, Garvan Institute of Medical Research, Sydney, NSW, Australia
- *Correspondence: Tian-Wen Xu, ; Shu Lin,
| | - Tian-Wen Xu
- Department of Digestive Tumours, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
- *Correspondence: Tian-Wen Xu, ; Shu Lin,
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Amelimojarad M, AmeliMojarad M, Nazemalhosseini-Mojarad E. Exosomal noncoding RNAs in colorectal cancer: An overview of functions, challenges, opportunities, and clinical applications. Pathol Res Pract 2022; 238:154133. [PMID: 36152568 DOI: 10.1016/j.prp.2022.154133] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 08/25/2022] [Accepted: 09/14/2022] [Indexed: 11/19/2022]
Abstract
Colorectal cancer (CRC) is the third most threatening malignancy worldwide. Colorectal tumors transfer information with their tumor microenvironment (TME) and communicate together which can be detected through exosome transmission. Exosomes are important regulators made by different types of cells in all body fluids containing RNA, DNA, metabolites, and proteins. Recently, Exosome-derived noncoding RNAs (ncRNAs) applications have gained great consideration based on their potential role in the different pathological processes. Therefore, in this review, we summarized the recent discoveries on exosomal ncRNAs function in CRC initiation and development, and drug resistance to provide a novel insight into exosomal ncRNAs' clinical application and their potential to be biomarkers for CRC patients.
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Affiliation(s)
- Melika Amelimojarad
- Gastrointestinal (GI) cancer Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mandana AmeliMojarad
- Gastrointestinal (GI) cancer Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Ehsan Nazemalhosseini-Mojarad
- Gastrointestinal (GI) cancer Department, 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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Ebrahimi N, Saremi J, Ghanaatian M, Yazdani E, Adelian S, Samsami S, Moradi N, Rostami Ravari N, Ahmadi A, Hamblin MR, Aref AR. The role of endoplasmic reticulum stress in the regulation of long noncoding RNAs in cancer. J Cell Physiol 2022; 237:3752-3767. [PMID: 35959643 DOI: 10.1002/jcp.30846] [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: 01/12/2022] [Revised: 07/17/2022] [Accepted: 07/19/2022] [Indexed: 11/09/2022]
Abstract
Cancer cells must overcome a variety of external and internal stresses to survive and proliferate. These unfavorable conditions include the accumulation of mutations, nutrient deficiency, oxidative stress, and hypoxia. These stresses can cause aggregation of misfolded proteins inside the endoplasmic reticulum. Under these conditions, the cell undergoes endoplasmic reticulum stress (ER-stress), and consequently initiates the unfolded protein response (UPR). Activation of the UPR triggers transcription factors and regulatory factors, including long noncoding RNAs (lncRNAs), which control the gene expression profile to maintain cellular stability and hemostasis. Recent investigations have shown that cancer cells can ensure their survival under adverse conditions by the UPR affecting the expression of lncRNAs. Therefore, understanding the relationship between lncRNA expression and ER stress could open new avenues, and suggest potential therapies to treat various types of cancer.
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Affiliation(s)
- Nasim Ebrahimi
- Genetics Division, Department of Cell and Molecular Biology and Microbiology, Faculty of Science and Technology, University of Isfahan, Isfahan, Iran
| | - Jamileh Saremi
- Research Center for Noncommunicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran
| | - Masoud Ghanaatian
- Department of Microbiology, Islamic Azad University of Jahrom, Jahrom, Iran
| | - Elnaz Yazdani
- Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Iran.,Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
| | - Samaneh Adelian
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Sahar Samsami
- Biotechnology Department of Fasa University of Medical Science, Fasa, Iran
| | - Neda Moradi
- Division of Biotechnology, Department of Cell and Molecular Biology and Microbiology, Nourdanesh Institute of Higher Education, University of Meymeh, Isfahan, Iran
| | - Nadi Rostami Ravari
- Department of Biology, Faculty of Science, Islamic Azad University, Kerman, Iran
| | - Amirhossein Ahmadi
- Department of Biological Science and Technology, Faculty of Nano and Bio Science and Technology, Persian Gulf University, Bushehr, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
| | - Amir Reza Aref
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.,Xsphera Biosciences, Translational Medicine group, 6 Tide Street, Boston, MA, 02210, USA
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Zhang Z, Zhu X. MiR-103a-3p Contributes to the Progression of Colorectal Cancer by Regulating GREM2 Expression. Yonsei Med J 2022; 63:520-529. [PMID: 35619575 PMCID: PMC9171664 DOI: 10.3349/ymj.2022.63.6.520] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 01/14/2022] [Accepted: 02/04/2022] [Indexed: 12/24/2022] Open
Abstract
PURPOSE Our research aimed to investigate the influence of miR-103a-3p on the growth and apoptosis of colorectal cancer (CRC) cells. MATERIALS AND METHODS Bioinformatics was employed to analyze differentially expressed microRNAs and predict target genes. qRT-PCR was applied to detect the expression of miR-103a-3p in CRC and normal cells. HCT116 and Caco-2 were chosen, and miR-103a-3p mimics, miR-103a-3p inhibitor, as well as specific siRNAs targeting GREM2, were constructed. We subsequently evaluated alternations in cell proliferation, cell cycle and cell cycle regulators, apoptosis, and related proteins (Bcl-2 and Bax) by CCK-8 testing, Western blotting, luciferase reporter, colony formation, and Annexin V-FITC/PI. Possible binding sites for miR-103a-3p on the 3'UTR of GREM2 were checked with luciferase assay, and the impact of GREM2 on miR-103a-3p activity was also validated with above biological function testing. Additionally, the effect of miR-103a-3p knockdown in CRC cells and the molecular mechanism of miR-103a-3p targeting GREM2 were also studied. RESULTS Bioinformatics analysis revealed that miR-103a-3p expression increased remarkably in CRC, and targeted regulatory correlation existed between miR-103a-3p and GREM2. MiR-103a-3p inhibitor significantly impeded proliferative capacity and caused cell cycle arrest, as well as apoptosis, in HCT116 and Caco-2 cells. Consistent with this finding, overexpression of GREM2 showed similar effects to miR-103a-3p inhibition. Moreover, we demonstrated that miR-103a-3p connected target GREM2 and GREM2 knockdown reversed the effects of miR-103a-3p inhibitor on HCT116 and Caco-2 cell proliferation, cell cycle, and apoptosis. Further study showed that miR-103a-3p targeting GREM2 appeared to affect CRC progression via the transforming growth factor-β pathway. CONCLUSION MiR-103a-3p could augment CRC progression by targeting GREM2 and that miR-103a-3p/GREM2 could be potential novel targets for CRC therapy.
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Affiliation(s)
- Zongxiang Zhang
- Department of General Surgery, Zhejiang Chinese Medicine and Western Medicine Integrated Hospital/Hangzhou Red Cross Hospital, Hangzhou, China
| | - Xiaolian Zhu
- Department of Medical Oncology, Zhuji People's Hospital of Zhejiang Province, Zhuji Affiliated Hospital of Shaoxing University, Zhuji, China.
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Hu Z, Zhou X, Zeng D, Lai J. Shikonin induces cell autophagy via modulating the microRNA -545-3p/guanine nucleotide binding protein beta polypeptide 1 axis, thereby disrupting cellular carcinogenesis in colon cancer. Bioengineered 2022; 13:5928-5941. [PMID: 35192430 PMCID: PMC8973937 DOI: 10.1080/21655979.2021.2024638] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/28/2021] [Accepted: 12/28/2021] [Indexed: 01/22/2023] Open
Abstract
Shikonin (SHK), a major component of shiverweed, was provided with anti-tumor effects via multiple targets and signal pathways. Nevertheless, the specific mechanism of its function in colorectal cancer (CRC) still needed to be further explored. The study was designed to examine the role of SHK in CRC and its specific mechanism on the cell tumor behavior of CRC. Collection of clinical samples was performed, and test of microRNA (miR)-545-3p and guanine nucleotide-binding protein beta polypeptide 1 (GNB1) in the samples was conducted; Selection of CRC cell line was exerted, and examination of miR-545-3p and GNB1 was performed; After treatment of shikonin (SHK), correlated plasmids were transfected, test of cell advancement was performed. Test of the protein of autophagy-correlated proteins light chain 3-II/light chain 3I and p63 was performed. The interaction of miR-545-3p with GNB1 was explored, and the action of SHK in vivo was tested. SHK repressed the advancement of SW480 cells with elevated apoptosis and autophagy and the cells quantities in G0/G1 phase. MiR-545-3p was elevated in CRC. SHK boosted miR-545-3p, repression of miR-545-3p or augmentation of GNB1 was able to turn around the function of SHK on CRC, and GNB1 was the target gene of miR-545-3p.All in all, SHK stimulates apoptosis and autophagy in CRC via miR-545-3p/GNB1 signaling axis, firstly demonstrating the regulatory mechanism of SHK in CRC via miR-545-3p/GNB1 axis.
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Affiliation(s)
- ZhiWei Hu
- Department of Gastrointestinal Surgery, The Yuebei People’s Hospital of ShaoGuan, ShaoGuan, GuangDong, China
| | - XinDong Zhou
- Department of Gastrointestinal Surgery, The Yuebei People’s Hospital of ShaoGuan, ShaoGuan, GuangDong, China
| | - DeQiang Zeng
- Department of Gastrointestinal Surgery, The Yuebei People’s Hospital of ShaoGuan, ShaoGuan, GuangDong, China
| | - JiaJun Lai
- Department of Gastrointestinal Surgery, The Yuebei People’s Hospital of ShaoGuan, ShaoGuan, GuangDong, China
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43
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Jorgensen BG, Ro S. MicroRNAs and 'Sponging' Competitive Endogenous RNAs Dysregulated in Colorectal Cancer: Potential as Noninvasive Biomarkers and Therapeutic Targets. Int J Mol Sci 2022; 23:2166. [PMID: 35216281 PMCID: PMC8876324 DOI: 10.3390/ijms23042166] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 01/28/2022] [Accepted: 02/02/2022] [Indexed: 12/13/2022] Open
Abstract
The gastrointestinal (GI) tract in mammals is comprised of dozens of cell types with varied functions, structures, and histological locations that respond in a myriad of ways to epigenetic and genetic factors, environmental cues, diet, and microbiota. The homeostatic functioning of these cells contained within this complex organ system has been shown to be highly regulated by the effect of microRNAs (miRNA). Multiple efforts have uncovered that these miRNAs are often tightly influential in either the suppression or overexpression of inflammatory, apoptotic, and differentiation-related genes and proteins in a variety of cell types in colorectal cancer (CRC). The early detection of CRC and other GI cancers can be difficult, attributable to the invasive nature of prophylactic colonoscopies. Additionally, the levels of miRNAs associated with CRC in biofluids can be contradictory and, therefore, must be considered in the context of other inhibiting competitive endogenous RNAs (ceRNA) such as lncRNAs and circRNAs. There is now a high demand for disease treatments and noninvasive screenings such as testing for bloodborne or fecal miRNAs and their inhibitors/targets. The breadth of this review encompasses current literature on well-established CRC-related miRNAs and the possibilities for their use as biomarkers in the diagnoses of this potentially fatal GI cancer.
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Affiliation(s)
| | - Seungil Ro
- Department of Physiology & Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA;
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44
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Lofft Z, Taibi A, Massara P, Tokar T, Paetau‐Robinson I, Khoo C, Comelli EM. Cranberry proanthocyanidin and its microbial metabolite 3,4‐dihydroxyphenylacetic acid, but not 3‐(4‐hydroxyphenyl)‐propionic acid, partially reverse pro‐inflammatory microRNA responses in human intestinal epithelial cells. Mol Nutr Food Res 2022; 66:e2100853. [DOI: 10.1002/mnfr.202100853] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 01/13/2022] [Indexed: 11/08/2022]
Affiliation(s)
- Zoe Lofft
- Department of Nutritional Sciences University of Toronto ON Canada
| | - Amel Taibi
- Department of Nutritional Sciences University of Toronto ON Canada
| | - Paraskevi Massara
- Department of Nutritional Sciences University of Toronto ON Canada
- Translational Medicine Program Hospital for Sick Children Toronto Canada
| | - Tomas Tokar
- Krembil Research Institute University Health Network Toronto ON M5T 0S8 Canada
| | | | - Christina Khoo
- Ocean Spray Cranberries, Inc. Lakeville‐Middleboro MA USA
| | - Elena M. Comelli
- Department of Nutritional Sciences University of Toronto ON Canada
- Joannah and Brian Lawson Centre for Child Nutrition University of Toronto ON Canada
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45
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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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Liu H, Bian QZ, Zhang W, Cui HB. Circulating microRNA-103a-3p could be a diagnostic and prognostic biomarker for breast cancer. Oncol Lett 2021; 23:38. [PMID: 34966454 PMCID: PMC8669650 DOI: 10.3892/ol.2021.13156] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 09/15/2021] [Indexed: 12/13/2022] Open
Abstract
Breast cancer (BC) is the most frequent cancer for women worldwide. Recently, a spectrum of cell-free circulating microRNAs (miR) has been recognized as promising biomarkers for BC diagnosis and prognosis, among which miR-103a-3p has been reported in several types of human cancer. However, the role of miR-103a-3p in BC remains unknown. A total of 112 patients with BC and 59 healthy controls were recruited into the present study. The expression level of serum miR-103a-3p was evaluated using reverse transcription-quantitative PCR. Receiver operating characteristic curves were utilized to calculate diagnostic accuracy. Survival curves were generated to analyze survival outcomes. It was found that circulating miR-103a-3p level was upregulated in patients with BC compared with that in healthy controls, and its expression was decreased following surgery. In addition, miR-103a-3p expression level was also associated with advanced clinicopathological features, including positive epidermal growth factor receptor 2 status, metastasis and an advanced TNM stage. The circulating serum miR-103a-3p level could be used to discriminate between patients with BC and the healthy controls prior to surgery using an area under curve [(AUC), 0.697; 95% confidence intervals (CI), 0.615-0.778], and distinguish patients with BC and metastasis from those without metastasis (AUC, 0.936; 95% CI, 0.892-0.980). In addition, high expression level of miR-103a-3p was associated with worse survival outcomes in patients with BC. In conclusion, the present study suggests that miR-103a-3p could be a potential non-invasive diagnostic and prognostic biomarker for BC.
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Affiliation(s)
- Hui Liu
- Department of Thyroid and Breast Surgery, Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China
| | - Qing-Zhao Bian
- Department of Thyroid and Breast Surgery, Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China
| | - Wei Zhang
- Department of Thyroid and Breast Surgery, Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China
| | - Hai-Bin Cui
- Department of Thyroid and Breast Surgery, Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China
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Wen R, Chen C, Zhong X, Hu C. PAX6 upstream antisense RNA (PAUPAR) inhibits colorectal cancer progression through modulation of the microRNA (miR)-17-5p / zinc finger protein 750 (ZNF750) axis. Bioengineered 2021; 12:3886-3899. [PMID: 34288812 PMCID: PMC8806802 DOI: 10.1080/21655979.2021.1940071] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Researchers have demonstrated that long non-coding RNAs (lncRNAs) are vital in colorectal cancer (CRC) progression. Here, we aimed to explore the function of lncRNA PAX6 upstream antisense RNA (PAUPAR) in the development of CRC. In the present study, PAUPAR and microRNA (miR)-17-5p expression levels in CRC tissues and cells were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Western blot analysis was adopted to examine ZNF750 expression at the protein level in CRC cells. CRC cell proliferation was examined by colony formation experiment and 5-Bromo-2-deoxyUridine (BrdU) experiment. CRC cell migration and invasion were assessed by Transwell experiments. Apoptosis was measured using the TUNEL experiment. The targeting relationship between PAUPAR and miR-17-5p was confirmed using dual-luciferase reporter gene and RNA immunoprecipitation (RIP) experiments. We demonstrated that PAUPAR was markedly down-modulated in CRC, and its low expression was significantly related to increased T stage and local lymph node metastasis. Knockdown of PAUPAR enhanced CRC cell proliferation, migration and invasion, and restrained apoptosis relative to controls, whereas PAUPAR overexpression caused the opposite effects. Moreover, rescue experiments showed that miR-17-5p inhibitor could reverse the role of PAUPAR knockdown on the malignant phenotypes of CRC cells. Additionally, PAUPAR could positively regulate the expression of ZNF750 via repressing miR-17-5p. Taken together, these findings suggest that PAUPAR/miR-17-5p/ZNF750 axis is a novel mechanism implicated in CRC progression.
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Affiliation(s)
- Ruhui Wen
- Department of Gastrointestinal Surgery, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China
- CONTACT Ruhui Wen Department of Gastrointestinal Surgery, Huizhou Municipal Central Hospital, NO. 41 Erling North Road, Huicheng District, Huizhou, Guangdong516000, China
| | - Chao Chen
- Department of Gastrointestinal Surgery, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China
| | - Xiaohua Zhong
- Department of Gastrointestinal Surgery, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China
| | - Chen Hu
- Department of Gastrointestinal Surgery, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China
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Almeida-Lousada H, Mestre A, Ramalhete S, Price AJ, de Mello RA, Marreiros AD, Neves RPD, Castelo-Branco P. Screening for Colorectal Cancer Leading into a New Decade: The "Roaring '20s" for Epigenetic Biomarkers? Curr Oncol 2021; 28:4874-4893. [PMID: 34898591 PMCID: PMC8628779 DOI: 10.3390/curroncol28060411] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 11/12/2021] [Accepted: 11/17/2021] [Indexed: 12/16/2022] Open
Abstract
Colorectal cancer (CRC) has an important bearing (top five) on cancer incidence and mortality in the world. The etiology of sporadic CRC is related to the accumulation of genetic and epigenetic alterations that result in the appearance of cancer hallmarks such as abnormal proliferation, evasion of immune destruction, resistance to apoptosis, replicative immortality, and others, contributing to cancer promotion, invasion, and metastasis. It is estimated that, each year, at least four million people are diagnosed with CRC in the world. Depending on CRC staging at diagnosis, many of these patients die, as CRC is in the top four causes of cancer death in the world. New and improved screening tests for CRC are needed to detect the disease at an early stage and adopt patient management strategies to decrease the death toll. The three pillars of CRC screening are endoscopy, radiological imaging, and molecular assays. Endoscopic procedures comprise traditional colonoscopy, and more recently, capsule-based endoscopy. The main imaging modality remains Computed Tomography (CT) of the colon. Molecular approaches continue to grow in the diversity of biomarkers and the sophistication of the technologies deployed to detect them. What started with simple fecal occult blood tests has expanded to an armamentarium, including mutation detection and identification of aberrant epigenetic signatures known to be oncogenic. Biomarker-based screening methods have critical advantages and are likely to eclipse the classical modalities of imaging and endoscopy in the future. For example, imaging methods are costly and require highly specialized medical personnel. In the case of endoscopy, their invasiveness limits compliance from large swaths of the population, especially those with average CRC risk. Beyond mere discomfort and fear, there are legitimate iatrogenic concerns associated with endoscopy. The risks of perforation and infection make endoscopy best suited for a confirmatory role in cases where there are positive results from other diagnostic tests. Biomarker-based screening methods are largely non-invasive and are growing in scope. Epigenetic biomarkers, in particular, can be detected in feces and blood, are less invasive to the average-risk patient, detect early-stage CRC, and have a demonstrably superior patient follow-up. Given the heterogeneity of CRC as it evolves, optimal screening may require a battery of blood and stool tests, where each can leverage different pathways perturbed during carcinogenesis. What follows is a comprehensive, systematic review of the literature pertaining to the screening and diagnostic protocols used in CRC. Relevant articles were retrieved from the PubMed database using keywords including: "Screening", "Diagnosis", and "Biomarkers for CRC". American and European clinical trials in progress were included as well.
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Affiliation(s)
- Hélder Almeida-Lousada
- Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal; (H.A.-L.); (A.M.); (S.R.); (R.A.d.M.); (A.D.M.)
- Algarve Biomedical Center Research Institute (ABC-RI), 8005-139 Faro, Portugal
| | - André Mestre
- Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal; (H.A.-L.); (A.M.); (S.R.); (R.A.d.M.); (A.D.M.)
- Algarve Biomedical Center Research Institute (ABC-RI), 8005-139 Faro, Portugal
| | - Sara Ramalhete
- Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal; (H.A.-L.); (A.M.); (S.R.); (R.A.d.M.); (A.D.M.)
- Algarve Biomedical Center Research Institute (ABC-RI), 8005-139 Faro, Portugal
| | - Aryeh J. Price
- School of Law, University of California, Berkeley, CA 94704, USA;
| | - Ramon Andrade de Mello
- Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal; (H.A.-L.); (A.M.); (S.R.); (R.A.d.M.); (A.D.M.)
- Division of Medical Oncology, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo 04037-004, Brazil
- Precision Oncology & Health Economics Group (ONCOPRECH), Post-Graduation Program in Medicine, Nine of July University (UNINOVE), São Paulo 01525-000, Brazil
| | - Ana D. Marreiros
- Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal; (H.A.-L.); (A.M.); (S.R.); (R.A.d.M.); (A.D.M.)
- Algarve Biomedical Center Research Institute (ABC-RI), 8005-139 Faro, Portugal
| | - Ricardo Pires das Neves
- CNC—Center for Neuroscience and Cell Biology, CIBB—Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal
- IIIUC—Institute of Interdisciplinary Research, University of Coimbra, 3004-517 Coimbra, Portugal
| | - Pedro Castelo-Branco
- Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal; (H.A.-L.); (A.M.); (S.R.); (R.A.d.M.); (A.D.M.)
- Algarve Biomedical Center Research Institute (ABC-RI), 8005-139 Faro, Portugal
- Champalimaud Research Program, Champalimaud Center for the Unknown, 1400-038 Lisbon, Portugal
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Cheng X, Wei H, Zhang S, Zhang F. Predictive and Prognostic Value of an MicroRNA Signature for Gastric Carcinoma Undergoing Adjuvant Chemotherapy. DNA Cell Biol 2021; 40:1428-1444. [PMID: 34767733 DOI: 10.1089/dna.2021.0377] [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: 11/13/2022] Open
Abstract
Gastric carcinoma (GC) is one of the most common cause of tumor-related death. Chemotherapy resistance usually occurs, leading to cancer relapse and poor survival of GC patients. To investigate the role of miRNAs in chemotherapy resistance for GC patients, we conducted an integrated analysis of miRNA expression and survival information using data obtained from The Cancer Genome Atlas project. Genome-wide screening of chemotherapy response-specific miRNAs was performed using Cox proportional hazards regression analyses for patients who received chemotherapy or those who had never received chemotherapy, respectively. A four-miRNA expression signature (involving two protective miRNAs, miR-200b and miR-103a, and two risk ones miR-199 and miR-152) was predicted as a specific indicator for GC chemoresistance (p = 0.00053; hazard ratio = 8.63), outperforming those clinicopathological factors. Functional experiments confirmed the roles of these signature miRNAs in regulation of chemotherapy response. Functional enrichment of these signature miRNAs and risk score revealed positive association with epithelial-mesenchymal transition (EMT), and negative association with cell cycle checkpoint and DNA damage response. Furthermore, the immune infiltration-miRNA functional network analysis revealed transformation from activated effector cells to resting immunosuppressive cells are preferred in GCs with adverse chemotherapy response. In summary, our work identifies a four-miRNA expression signature as a promising chemoresistance biomarker in GC, which provides novel insights into developing new strategies to overcome GC chemoresistance.
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Affiliation(s)
- Xiaowei Cheng
- Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi City, People's Republic of China
| | - Hongkuang Wei
- The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning City, People's Republic of China
| | - Sheng Zhang
- Wuxi Eighth People's Hospital, Wuxi City, People's Republic of China
| | - Fuzheng Zhang
- Department of Radiation Oncology, Affiliated Hospital of Jiangnan University, Wuxi City, People's Republic of China
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Sayyed AA, Gondaliya P, Bhat P, Mali M, Arya N, Khairnar A, Kalia K. Role of miRNAs In Cancer Diagnostics And Therapy: A Recent Update. Curr Pharm Des 2021; 28:471-487. [PMID: 34751112 DOI: 10.2174/1381612827666211109113305] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 07/16/2021] [Indexed: 12/15/2022]
Abstract
The discovery of miRNAs has been one of the revolutionary developments and has led to the advent of new diagnostic and therapeutic opportunities for the management of cancer. In this regard, miRNA dysregulation has been shown to play a critical role in various stages of tumorigenesis, including tumor invasion, metastasis as well as angiogenesis. Therefore, miRNA profiling can provide accurate fingerprints for the development of diagnostic and therapeutic platforms. This review discusses the recent discoveries of miRNA-based tools for early detection of cancer as well as disease monitoring in cancers that are common, like breast, lung, hepatic, colorectal, oral and brain cancer. Based on the involvement of miRNA in different cancers as oncogenic miRNA or tumor suppressor miRNA, the treatment with miRNA inhibitors or mimics is recommended. However, the stability and targeted delivery of miRNA remain the major limitations of miRNA delivery. In relation to this, several nanoparticle-based delivery systems have been reported which have effectively delivered the miRNA mimics or inhibitors and showed the potential for transforming these advanced delivery systems from bench to bedside in the treatment of cancer metastasis and chemoresistance. Based on this, we attempted to uncover recently reported advanced nanotherapeutic approaches to deliver the miRNAs in the management of different cancers.
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Affiliation(s)
- Adil A Sayyed
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Ahmedabad, Gujarat. India
| | - Piyush Gondaliya
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Ahmedabad, Gujarat. India
| | - Palak Bhat
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Ahmedabad, Gujarat. India
| | - Mukund Mali
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Ahmedabad, Gujarat. India
| | - Neha Arya
- Department of Medical Devices, National Institute of Pharmaceutical Education and Research, Ahmedabad, Gujarat. India
| | - Amit Khairnar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Ahmedabad, Gujarat. India
| | - Kiran Kalia
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Ahmedabad, Gujarat. India
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