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Růžičková T, Vlachová M, Pečinka L, Brychtová M, Večeřa M, Radová L, Ševčíková S, Jarošová M, Havel J, Pour L, Ševčíková S. Detection of early relapse in multiple myeloma patients. Cell Div 2025; 20:4. [PMID: 39881385 PMCID: PMC11776158 DOI: 10.1186/s13008-025-00143-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 01/19/2025] [Indexed: 01/31/2025] Open
Abstract
BACKGROUND Multiple myeloma (MM) represents the second most common hematological malignancy characterized by the infiltration of the bone marrow by plasma cells that produce monoclonal immunoglobulin. While the quality and length of life of MM patients have significantly increased, MM remains a hard-to-treat disease; almost all patients relapse. As MM is highly heterogenous, patients relapse at different times. It is currently not possible to predict when relapse will occur; numerous studies investigating the dysregulation of non-coding RNA molecules in cancer suggest that microRNAs could be good markers of relapse. RESULTS Using small RNA sequencing, we profiled microRNA expression in peripheral blood in three groups of MM patients who relapsed at different intervals. In total, 24 microRNAs were significantly dysregulated among analyzed subgroups. Independent validation by RT-qPCR confirmed changed levels of miR-598-3p in MM patients with different times to relapse. At the same time, differences in the mass spectra between groups were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry. All results were analyzed by machine learning. CONCLUSION Mass spectrometry coupled with machine learning shows potential as a reliable, rapid, and cost-effective preliminary screening technique to supplement current diagnostics.
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Affiliation(s)
- Tereza Růžičková
- Babak Myeloma Group, Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic
| | - Monika Vlachová
- Babak Myeloma Group, Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Lukáš Pečinka
- Research Centre for Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute, Brno, Czech Republic
- International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic
| | - Monika Brychtová
- Babak Myeloma Group, Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Marek Večeřa
- Centre for Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic
| | - Lenka Radová
- Centre for Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic
| | - Simona Ševčíková
- Babak Myeloma Group, Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Marie Jarošová
- Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic
| | - Josef Havel
- Department of Chemistry, Faculty of Science, Masaryk University, Brno, Czech Republic
| | - Luděk Pour
- Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic
| | - Sabina Ševčíková
- Babak Myeloma Group, Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
- Department of Clinical Hematology, University Hospital Brno, Brno, Czech Republic.
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Aboutalebi Vand Beilankouhi E, Sanaat Z, Hosseinpour Feizi MA, Mehdizadeh A, Safaralizadeh R. Investigation of circulating miR-182-3p, miR -382-3p and miR -93, miR -142-3p involved in tamoxifen resistance and sensitivity in luminal-subtype breast cancer patients: a case-control study. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-024-03770-9. [PMID: 39754680 DOI: 10.1007/s00210-024-03770-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 12/26/2024] [Indexed: 01/06/2025]
Abstract
Breast cancer (BC) commonly expresses estrogen receptors (ERs); hence, endocrine therapy targeting ERs is considered an effective treatment. Tamoxifen (TAM) resistance is an essential clinical complication leading to cancer progression and metastasis. This study investigated MicroRNAs (miRNAs) potentially implicated in drug resistance (miR-182-3p, miR-382-3p) or sensitivity (miR-93, miR- 142- 3p). This study aimed to provide new insights into serum microRNA expression profiles in BC. This case-control study included patients with luminal-A BC who received TAM for approximately one year. The case and control groups included 40 patients with or without local recurrence or metastasis. The expression levels of miR-182-3p, miR-382-3p, miR-93, and miR-142-3p in plasma samples were measured using real-time PCR with target-specific primers. The multivariate model of miR-93 (p = 0.0002), miR-182-3p (p = 0.0002), and miR-382-3p (p = 0.0028) demonstrated higher predictive power for TAM resistance. The only significant association was observed between miR-382-3p expression and lymphovascular invasion (LVI) (p = 0.0314). Moreover, lower expression levels of miR-93 and miR-382-3p were observed in the TAM-sensitive group compared to the TAM-resistant counterparts (p = 0.0002 and p = 0.0028, respectively). In contrast, the expression level of miR-182-3p was significantly higher in the TAM-sensitive group compared to the TAM-resistant group (p = 0.0002). receiver operating characteristic (ROC) curve analysis also indicated the expression of miR-182-3p (p < 0.001; area under curve (AUC): 0.753), miR-382-3p (p = 0.0028; AUC: 0.697), and miR-93 (p < 0.001; AUC: 0.762) as predictive markers for TAM resistance. Multivariate models based on miR-182-3p, miR-382-3p, and miR-93 can predict the response to hormone therapy. Measuring these miRNAs is also recommended for patients with luminal-subtype BC undergoing TAM therapy.
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Affiliation(s)
| | - Zohreh Sanaat
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Amir Mehdizadeh
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Reza Safaralizadeh
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
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3
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Yang F, Guo Z, Wu J, Lu X. Circ-ITCH inhibits bladder cancer progression through miR-184/FOXO3 axis. Am J Transl Res 2024; 16:7911-7923. [PMID: 39822512 PMCID: PMC11733359 DOI: 10.62347/xbrv7186] [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: 07/21/2024] [Accepted: 10/24/2024] [Indexed: 01/19/2025]
Abstract
OBJECTIVE This study aimed to explore the role of circ-ITCH in the progression of bladder cancer (BCa). METHODS Kaplan-Meier analysis was performed to evaluate the prognostic significance of miR-184 in bladder cancer. Clustering analysis compared miR-184 expression levels across various BCa cell lines. Cell Counting Kit-8 (CCK-8) and transwell assays were used to assess cell proliferation and migration. Dual-luciferase reporter assays were employed to examine the regulatory relationship among circ-ITCH, miR-184, and FOXO3. Western blot analysis was conducted to investigate the post-transcriptional regulation of the circ-ITCH/miR-184/FOXO3 axis. RESULTS The study demonstrated a correlation between elevated miR-184 expression and poor prognosis in bladder cancer. Compared to SV-HUC, a normal bladder tissue cell line, most BCa cell lines exhibited increased miR-184 expression. Additionally, miR-184 was found to promote BCa cell progression. Importantly, circ-ITCH was identified as a natural sponge for miR-184 in BCa. Overexpression of circ-ITCH in BCa significantly reduced miR-184 expression, thereby inhibiting cell proliferation and migration. Moreover, FOXO3, a target of miR-184, is regulated by circ-ITCH. The suppression of FOXO3 by miR-184 was counteracted by circ-ITCH, which diminished the tumor-promoting effects of miR-184. CONCLUSIONS This study underscores the pivotal role of the circ-ITCH/miR-184/FOXO3 axis in regulating BCa cell proliferation and migration. It introduces a potential therapeutic target for bladder cancer, suggesting that strategies like circ-ITCH overexpression and miR-184 inhibition could offer promising treatment options.
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Affiliation(s)
- Fan Yang
- Department of Urology, Minhang Hospital, Fudan University Shanghai 201199, China
| | - Zhuifeng Guo
- Department of Urology, Minhang Hospital, Fudan University Shanghai 201199, China
| | - Jiawen Wu
- Department of Urology, Minhang Hospital, Fudan University Shanghai 201199, China
| | - Xuwei Lu
- Department of Urology, Minhang Hospital, Fudan University Shanghai 201199, China
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4
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Samsami Y, Akhlaghipour I, Taghehchian N, Palizkaran Yazdi M, Farrokhi S, Rahimi HR, Moghbeli M. MicroRNA-382 as a tumor suppressor during tumor progression. Bioorg Med Chem Lett 2024; 113:129967. [PMID: 39293533 DOI: 10.1016/j.bmcl.2024.129967] [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: 06/12/2024] [Revised: 08/27/2024] [Accepted: 09/13/2024] [Indexed: 09/20/2024]
Abstract
Despite the recent progresses in therapeutic and diagnostic methods, there is still a significantly high rate of mortality among cancer patients. One of the main reasons for the high mortality rate in cancer patients is late diagnosis, which leads to the failure of therapeutic strategies. Therefore, investigation of cancer biology can lead to the introduction of early diagnostic markers in these patients. MicroRNAs (miRNAs) play an important role in regulation of cellular processes associated with tumor progression. Due to the high stability of miRNAs in body fluids, these factors can be considered as the non-invasive tumor markers. Deregulation of miR-382 has been widely reported in different cancers. Therefore, in this review, we investigated the role of miR-382 during tumor development. It has shown that miR-382 has mainly a tumor suppressive, which inhibits the growth of tumor cells through the regulation of signaling pathways, RNA-binding proteins, and transcription factors. Therefore, miR-382 can be suggested as a diagnostic and therapeutic marker in cancer patients.
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Affiliation(s)
- Yalda Samsami
- Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Iman Akhlaghipour
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Negin Taghehchian
- Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Saba Farrokhi
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamid Reza Rahimi
- Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Moghbeli
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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5
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Alshamrani AA, Bin Salman SB, Alsaleh NB, Assiri MA, Almutairi MM, Almudimeegh S, Alwhaibi A, As Sobeai HM. miRNA-driven sensitization of breast cancer cells to Doxorubicin treatment following exposure to low dose of Zinc Oxide nanoparticles. Saudi Pharm J 2024; 32:102169. [PMID: 39318640 PMCID: PMC11421238 DOI: 10.1016/j.jsps.2024.102169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 09/04/2024] [Indexed: 09/26/2024] Open
Abstract
The impact of Engineered nanomaterials (ENMs) (i.e., Zinc Oxide nanoparticles (ZnO NPs)) on human health has been investigated at high and unrealistic exposure levels, overlooking the potential indirect harm of subtoxic and long exposures. Therefore, this study aimed to investigate the impacts of subtoxic concentrations of zinc oxide (ZnO NPs) on breast cancer cells' response to Doxorubicin. Zinc oxide nanoparticles caused a concentration-dependent reduction of cell viability in multiple breast cancer cell lines. A subtoxic concentration of 1.56 µg/mL (i.e., no observed adverse effect level) was used in subsequent mechanistic studies. Molecularly, miRNA profiling revealed significant downregulation of 13 oncogenic miRNAs (OncomiRs) in cells exposed to the sub-toxic dose of ZnO NPs followed by doxorubicin treatment. Our comprehensive bioinformatic analysis has identified 617 target genes enriched in ten pathways, mainly regulating gene expression and transcription, cell cycle, and apoptotic cell death. Several tumor suppressor genes emerged as validated direct targets of the 13 OncomiRs, including TFDP2, YWHAG, SMAD2, SMAD4, CDKN1A, CDKN1B, BCL2L11, and TGIF2. This study insinuates the importance of miRNAs in regulating the responsiveness of cancer cells to chemotherapy. Our findings further indicate that being exposed to environmental ENMs, even at levels below toxicity, might still modulate cancer cells' response to chemotherapy, which highlights the need to reestablish endpoints of ENM exposure and toxicity in cancer patients receiving chemotherapeutics.
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Affiliation(s)
- Ali A. Alshamrani
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Sami B. Bin Salman
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Nasser B. Alsaleh
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Mohammed A. Assiri
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Mohammed M. Almutairi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Sultan Almudimeegh
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Abdulrahman Alwhaibi
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Homood M. As Sobeai
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
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Yadav M, Vaishkiar I, Sharma A, Shukla A, Mohan A, Girdhar M, Kumar A, Malik T, Mohan A. Oestrogen receptor positive breast cancer and its embedded mechanism: breast cancer resistance to conventional drugs and related therapies, a review. Open Biol 2024; 14:230272. [PMID: 38889771 DOI: 10.1098/rsob.230272] [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: 08/10/2023] [Accepted: 03/14/2024] [Indexed: 06/20/2024] Open
Abstract
Traditional medication and alternative therapies have long been used to treat breast cancer. One of the main problems with current treatments is that there is an increase in drug resistance in the cancer cells owing to genetic differences such as mutational changes, epigenetic changes and miRNA (microRNA) alterations such as miR-1246, miR-298, miR-27b and miR-33a, along with epigenetic modifications, such as Histone3 acetylation and CCCTC-Binding Factor (CTCF) hypermethylation for drug resistance in breast cancer cell lines. Certain forms of conventional drug resistance have been linked to genetic changes in genes such as ABCB1, AKT, S100A8/A9, TAGLN2 and NPM. This review aims to explore the current approaches to counter breast cancer, the action mechanism, along with novel therapeutic methods endowing potential drug resistance. The investigation of novel therapeutic approaches sheds light on the phenomenon of drug resistance including genetic variations that impact distinct forms of oestrogen receptor (ER) cancer, genetic changes, epigenetics-reported resistance and their identification in patients. Long-term effective therapy for breast cancer includes selective oestrogen receptor modulators, selective oestrogen receptor degraders and genetic variations, such as mutations in nuclear genes, epigenetic modifications and miRNA alterations in target proteins. Novel research addressing combinational therapies including maytansine, photodynamic therapy, guajadiol, talazoparib, COX2 inhibitors and miRNA 1246 inhibitors have been developed to improve patient survival rates.
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Affiliation(s)
- Manu Yadav
- Division of Genetics, ICAR- Indian Agricultural Research Institute , Pusa, New Delhi, India
| | - Ishita Vaishkiar
- Amity Institute of Biotechnology (AIB) University, Amity University Noida , Noida, India
| | - Ananya Sharma
- Department: Botany and Microbiology, Hemwati Nandan Bahuguna Garhwal University , Srinagar, India
| | - Akanksha Shukla
- School of Bioengineering and Biosciences, Lovely Professional University , Phagwara, Punjab, India
| | - Aradhana Mohan
- Department of Biomedical Engineering, University of Michigan , Ann Arbor, MI, USA
| | - Madhuri Girdhar
- Division of Research and Development, Lovely Professional University , Phagwara, Punjab, India
| | - Anil Kumar
- Gene Regulation Laboratory, National Institute of Immunology , New Delhi, India
| | - Tabarak Malik
- Department of Biomedical Sciences, Institute of Health, Jimma University , Jimma, Oromia 378, Ethiopia
| | - Anand Mohan
- School of Bioengineering and Biosciences, Lovely Professional University , Phagwara, Punjab, India
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7
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Fattahi M, Shahrabi S, Saadatpour F, Rezaee D, Beyglu Z, Delavari S, Amrolahi A, Ahmadi S, Bagheri-Mohammadi S, Noori E, Majidpoor J, Nouri S, Aghaei-Zarch SM, Falahi S, Najafi S, Le BN. microRNA-382 as a tumor suppressor? Roles in tumorigenesis and clinical significance. Int J Biol Macromol 2023; 250:125863. [PMID: 37467828 DOI: 10.1016/j.ijbiomac.2023.125863] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 06/30/2023] [Accepted: 07/15/2023] [Indexed: 07/21/2023]
Abstract
MicroRNAs (miRNAs) are small single-stranded RNAs belonging to a class of non-coding RNAs with an average length of 18-22 nucleotides. Although not able to encode any protein, miRNAs are vastly studied and found to play role in various human physiologic as well as pathological conditions. A huge number of miRNAs have been identified in human cells whose expression is straightly regulated with crucial biological functions, while this number is constantly increasing. miRNAs are particularly studied in cancers, where they either can act with oncogenic function (oncomiRs) or tumor-suppressors role (referred as tumor-suppressor/oncorepressor miRNAs). miR-382 is a well-studied miRNA, which is revealed to play regulatory roles in physiological processes like osteogenic differentiation, hematopoietic stem cell differentiation and normal hematopoiesis, and liver progenitor cell differentiation. Notably, miR-382 deregulation is reported in pathologic conditions, such as renal fibrosis, muscular dystrophies, Rett syndrome, epidural fibrosis, atrial fibrillation, amelogenesis imperfecta, oxidative stress, human immunodeficiency virus (HIV) replication, and various types of cancers. The majority of oncogenesis studies have claimed miR-382 downregulation in cancers and suppressor impact on malignant phenotype of cancer cells in vitro and in vivo, while a few studies suggest opposite findings. Given the putative role of this miRNA in regulation of oncogenesis, assessment of miR-382 expression is suggested in a several clinical investigations as a prognostic/diagnostic biomarker for cancer patients. In this review, we have an overview to recent studies evaluated the role of miR-382 in oncogenesis as well as its clinical potential.
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Affiliation(s)
- Mehdi Fattahi
- Institute of Research and Development, Duy Tan University, Da Nang, Vietnam; School of Engineering & Technology, Duy Tan University, Da Nang, Vietnam
| | - Saeid Shahrabi
- Department of Biochemistry and Hematology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Fatemeh Saadatpour
- Pharmaceutical Biotechnology Lab, Department of Microbiology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran
| | - Delsuz Rezaee
- School of Allied Medical Sciences, Ilam University of Medical Sciences, Ilam, Iran
| | - Zahra Beyglu
- Department of Genetics, Qom Branch, Islamic Azad University, Qom, Iran
| | - Sana Delavari
- Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Anita Amrolahi
- Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Shirin Ahmadi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeid Bagheri-Mohammadi
- Department of Physiology and Neurophysiology Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Effat Noori
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Jamal Majidpoor
- Department of Anatomy, Faculty of Medicine, Infectious Disease Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Shadi Nouri
- Department of Radiology, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
| | - Seyed Mohsen Aghaei-Zarch
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Shahab Falahi
- Zoonotic Diseases Research Center, Ilam University of Medical Sciences, Ilam, Iran.
| | - Sajad Najafi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Binh Nguyen Le
- Institute of Research and Development, Duy Tan University, Da Nang, Vietnam; School of Engineering & Technology, Duy Tan University, Da Nang, Vietnam
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8
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El-Toukhy SE, El-Daly SM, Kamel MM, Nabih HK. The diagnostic significance of circulating miRNAs and metabolite profiling in early prediction of breast cancer in Egyptian women. J Cancer Res Clin Oncol 2023; 149:5437-5451. [PMID: 36459290 PMCID: PMC10349790 DOI: 10.1007/s00432-022-04492-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 11/21/2022] [Indexed: 12/03/2022]
Abstract
OBJECTIVE Breast cancer (BC) is one of the most commonly diagnosed solid malignancies in women worldwide. PURPOSE Finding new non-invasive circulating diagnostic biomarkers will facilitate the early prediction of BC and provide valuable insight into disease progression and response to therapy using a safe and more accessible approach available every inspection time. Therefore, our present study aimed to investigate expression patterns of potentially circulating biomarkers that can differentiate well between benign, malignant, and healthy subjects. METHODS To achieve our target, quantitative analyses were performed for some circulating biomarkers which have a role in the proliferation and tumor growth, as well as, glutamic acid, and human epidermal growth receptor 2 (HER2) in blood samples of BC patients in comparison to healthy controls using qRT-PCR, liquid chromatography/mass spectrometry (LC/MS/MS), and ELISA. RESULTS Our findings showed that the two miRNAs (miRNA-145, miRNA-382) were expressed at lower levels in BC sera than healthy control group, while miRNA-21 was expressed at higher levels in BC patients than control subjects. Area under ROC curves of BC samples revealed that AUC of miRNA-145, miRNA-382, miRNA-21, and glutamic acid was evaluated to equal 0.99, 1.00, 1.00 and 1.00, respectively. Besides, there was a significantly positive correlation between miRNA-145 and miRNA-382 (r = 0.737), and a highly significant positive correlation between miRNA-21 and glutamic acid (r = 0.385). CONCLUSION Based on our results, we conclude that the detection of serum miRNA-145, -382 and -21 as a panel along with glutamic acid, and circulating HER2 concentrations could be useful as a non-invasive diagnostic profiling for early prediction of breast cancer in Egyptian patients. It can provide an insight into disease progression, discriminate between malignancy and healthy control, and overcome the use limitations (low sensitivity and specificity, repeated risky exposure, and high cost) of other detecting tools, including mammography, magnetic resonance imaging, and ultrasound.
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Affiliation(s)
- Safinaz E El-Toukhy
- Medical Biochemistry Department, Medicine and Clinical Studies Research Institute, National Research Centre, 33 El-Bohouth st., Dokki, P.O. 12622, Giza, Egypt
| | - Sherien M El-Daly
- Medical Biochemistry Department, Medicine and Clinical Studies Research Institute, National Research Centre, 33 El-Bohouth st., Dokki, P.O. 12622, Giza, Egypt
- Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt
| | - Mahmoud M Kamel
- Laboratory Department, Baheya Hospital for Early Detection and Treatment of Breast Cancer, National Cancer Institute, Cairo University, Giza, Egypt
| | - Heba K Nabih
- Medical Biochemistry Department, Medicine and Clinical Studies Research Institute, National Research Centre, 33 El-Bohouth st., Dokki, P.O. 12622, Giza, Egypt.
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9
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Padroni L, De Marco L, Dansero L, Fiano V, Milani L, Vasapolli P, Manfredi L, Caini S, Agnoli C, Ricceri F, Sacerdote C. An Epidemiological Systematic Review with Meta-Analysis on Biomarker Role of Circulating MicroRNAs in Breast Cancer Incidence. Int J Mol Sci 2023; 24:3910. [PMID: 36835336 PMCID: PMC9967215 DOI: 10.3390/ijms24043910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/06/2023] [Accepted: 02/09/2023] [Indexed: 02/17/2023] Open
Abstract
Breast cancer (BC) is a multifactorial disease caused by an interaction between genetic predisposition and environmental exposures. MicroRNAs are a group of small non-coding RNA molecules, which seem to have a role either as tumor suppressor genes or oncogenes and seem to be related to cancer risk factors. We conducted a systematic review and meta-analysis to identify circulating microRNAs related to BC diagnosis, paying special attention to methodological problems in this research field. A meta-analysis was performed for microRNAs analyzed in at least three independent studies where sufficient data to make analysis were presented. Seventy-five studies were included in the systematic review. A meta-analysis was performed for microRNAs analyzed in at least three independent studies where sufficient data to make analysis were presented. Seven studies were included in the MIR21 and MIR155 meta-analysis, while four studies were included in the MIR10b metanalysis. The pooled sensitivity and specificity of MIR21 for BC diagnosis were 0.86 (95%CI 0.76-0.93) and 0.84 (95%CI 0.71-0.92), 0.83 (95%CI 0.72-0.91) and 0.90 (95%CI 0.69-0.97) for MIR155, and 0.56 (95%CI 0.32-0.71) and 0.95 (95%CI 0.88-0.98) for MIR10b, respectively. Several other microRNAs were found to be dysregulated, distinguishing BC patients from healthy controls. However, there was little consistency between included studies, making it difficult to identify specific microRNAs useful for diagnosis.
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Affiliation(s)
- Lisa Padroni
- Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Via Santena 7, 10126 Turin, Italy
| | - Laura De Marco
- Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Via Santena 7, 10126 Turin, Italy
| | - Lucia Dansero
- Centre for Biostatistics, Epidemiology and Public Health (C-BEPH), Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy
| | - Valentina Fiano
- Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
| | - Lorenzo Milani
- Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Via Santena 7, 10126 Turin, Italy
| | - Paolo Vasapolli
- Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
| | - Luca Manfredi
- Centre for Biostatistics, Epidemiology and Public Health (C-BEPH), Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy
| | - Saverio Caini
- Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy
| | - Claudia Agnoli
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
| | - Fulvio Ricceri
- Centre for Biostatistics, Epidemiology and Public Health (C-BEPH), Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy
- Unit of Epidemiology, Regional Health Service ASL TO3, 10095 Grugliasco, Italy
| | - Carlotta Sacerdote
- Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Via Santena 7, 10126 Turin, Italy
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10
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Breast cancer tumor microenvironment affects Treg/IL-17-producing Treg/Th17 cell axis: Molecular and therapeutic perspectives. Mol Ther Oncolytics 2023; 28:132-157. [PMID: 36816749 PMCID: PMC9922830 DOI: 10.1016/j.omto.2023.01.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
The tumor microenvironment (TME) comprises a variety of immune cells, among which T cells exert a prominent axial role in tumor development or anti-tumor responses in patients with breast cancer (BC). High or low levels of anti-inflammatory cytokines, such as transforming growth factor β, in the absence or presence of proinflammatory cytokines, such as interleukin-6 (IL-6), delineate the fate of T cells toward either regulatory T (Treg) or T helper 17 (Th17) cells, respectively. The transitional state of RORγt+Foxp3+ Treg (IL-17-producing Treg) resides in the middle of this reciprocal polarization, which is known as Treg/IL-17-producing Treg/Th17 cell axis. TME secretome, including microRNAs, cytokines, and extracellular vesicles, can significantly affect this axis. Furthermore, immune checkpoint inhibitors may be used to reconstruct immune cells; however, some of these novel therapies may favor tumor development. Therefore, understanding secretory and cell-associated factors involved in their differentiation or polarization and functions may be targeted for BC management. This review discusses microRNAs, cytokines, and extracellular vesicles (as secretome), as well as transcription factors and immune checkpoints (as cell-associated factors), which influence the Treg/IL-17-producing Treg/Th17 cell axis in BC. Furthermore, approved or ongoing clinical trials related to the modulation of this axis in the TME of BC are described to broaden new horizons of promising therapeutic approaches.
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11
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Lin H, Guo X, Yang F, Yu L, Wen R, Zhang X. MiR-598-5p inhibits breast cancer tumor growth and lung metastasis by targeting PPAPDC1A. CHINESE J PHYSIOL 2023; 66:103-110. [PMID: 37026213 DOI: 10.4103/cjop.cjop-d-22-00089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/05/2023] Open
Abstract
This study aimed to explore the effects of PPAPDC1A on the malignant phenotype of breast cancer (BC) in vivo and in vitro. PPAPDC1A expression was examined in BC tissues and cell lines by real-time polymerase chain reaction and Western blot. In this article, cell proliferation was evaluated by Cell Counting Kit-8 assay and colony formation assay, and cell migration and invasion were evaluated by wound healing assay and transwell assays. Furthermore, in vivo cell growth and pulmonary metastasis experiments were also performed using nude mice. The results showed that compared with normal tissues and cells, the PPAPDC1A expression in BC tissues and cell lines were both significantly increased. The PPAPDC1A targeting sequence significantly inhibited the PPAPDC1A expression and cell proliferation, migration, and invasion. The results of xenograft showed that knockdown of PPAPDC1A inhibited tumor growth and lung metastasis of BC. Then, the Dual-Luciferase Reporter Assay confirmed that miR-598-5p targeted the regulation of PPAPDC1A expression. In addition, the miR-598-5p expression in BC tissues was lower than that in the normal tissues. The rescue experiment showed that PPAPDC1A overexpression reversed the inhibitory effect of miR-598-5p mimic on cell proliferation, migration, and invasion. In conclusion, PPAPDC1A was highly expressed in BC tissues and cell lines, and miR-598-5p inhibited the malignant phenotype of BC by targeting PPAPDC1A.
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12
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Huynh KQ, Le AT, Phan TT, Ho TT, Pho SP, Nguyen HT, Le BT, Nguyen TT, Nguyen ST. The Diagnostic Power of Circulating miR-1246 in Screening Cancer: An Updated Meta-analysis. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2023; 2023:8379231. [PMID: 37122536 PMCID: PMC10139802 DOI: 10.1155/2023/8379231] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 03/28/2023] [Accepted: 04/11/2023] [Indexed: 05/02/2023]
Abstract
Background MicroRNA-1246 (miR-1246), an oncomiR that regulates the expression of multiple cancer-related genes, has been attracted and studied as a promising indicator of various tumors. However, diverse conclusions on diagnostic accuracy have been shown due to the small sample size and limited studies included. This meta-analysis is aimed at systematically assessing the performance of extracellular circulating miR-1246 in screening common cancers. Methods We searched the PubMed/MEDLINE, Web of Science, Cochrane Library, and Google Scholar databases for relevant studies until November 28, 2022. Then, the summary receiver operating characteristic (SROC) curves were drawn and calculated area under the curve (AUC), diagnostic odds ratio (DOR), sensitivity, and specificity values of circulating miR-1246 in the cancer surveillance. Results After selection and quality assessment, 29 eligible studies with 5914 samples (3232 cases and 2682 controls) enrolled in the final analysis. The pooled AUC, DOR, sensitivity, and specificity of circulating miR-1246 in screening cancers were 0.885 (95% confidence interval (CI): 0.827-0.892), 27.7 (95% CI: 17.1-45.0), 84.2% (95% CI: 79.4-88.1), and 85.3% (95% CI: 80.5-89.2), respectively. Among cancer types, superior performance was noted for breast cancer (AUC = 0.950, DOR = 98.5) compared to colorectal cancer (AUC = 0.905, DOR = 47.6), esophageal squamous cell carcinoma (AUC = 0.757, DOR = 8.0), hepatocellular carcinoma (AUC = 0.872, DOR = 18.6), pancreatic cancer (AUC = 0.767, DOR = 12.3), and others (AUC = 0.887, DOR = 27.5, P = 0.007). No significant publication bias in DOR was observed in the meta-analysis (funnel plot asymmetry test with P = 0.652; skewness value = 0.672, P = 0.071). Conclusion Extracellular circulating miR-1246 may serve as a reliable biomarker with good sensitivity and specificity in screening cancers, especially breast cancer.
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Affiliation(s)
- Khanh Quang Huynh
- The Breast Unit, Cancer Center, Cho Ray Hospital, HCMC 700000, Vietnam
| | - Anh Tuan Le
- Department of Chemo-Radiotherapy, Cancer Center, Cho Ray Hospital, HCMC 700000, Vietnam
| | - Thang Thanh Phan
- The Laboratory D Unit, Cancer Center, Cho Ray Hospital, HCMC 700000, Vietnam
| | - Toan Trong Ho
- The Laboratory D Unit, Cancer Center, Cho Ray Hospital, HCMC 700000, Vietnam
| | - Suong Phuoc Pho
- The Laboratory D Unit, Cancer Center, Cho Ray Hospital, HCMC 700000, Vietnam
| | - Hang Thuy Nguyen
- Department of Clinical Pathology, Cho Ray Hospital, HCMC 700000, Vietnam
| | - Binh Thanh Le
- Department of General Director, Cho Ray Hospital, HCMC 700000, Vietnam
| | - Thuc Tri Nguyen
- Department of General Director, Cho Ray Hospital, HCMC 700000, Vietnam
| | - Son Truong Nguyen
- Department of General Director, Cho Ray Hospital, HCMC 700000, Vietnam
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13
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Feng L, Guo L, Tanaka Y, Su L. Tumor-Derived Small Extracellular Vesicles Involved in Breast Cancer Progression and Drug Resistance. Int J Mol Sci 2022; 23:ijms232315236. [PMID: 36499561 PMCID: PMC9736664 DOI: 10.3390/ijms232315236] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 11/28/2022] [Accepted: 12/01/2022] [Indexed: 12/09/2022] Open
Abstract
Breast cancer is one of the most serious and terrifying threats to the health of women. Recent studies have demonstrated that interaction among cancer cells themselves and those with other cells, including immune cells, in a tumor microenvironment potentially and intrinsically regulate and determine cancer progression and metastasis. Small extracellular vesicles (sEVs), a type of lipid-bilayer particles derived from cells, with a size of less than 200 nm, are recognized as one form of important mediators in cell-to-cell communication. sEVs can transport a variety of bioactive substances, including proteins, RNAs, and lipids. Accumulating evidence has revealed that sEVs play a crucial role in cancer development and progression, with a significant impact on proliferation, invasion, and metastasis. In addition, sEVs systematically coordinate physiological and pathological processes, such as coagulation, vascular leakage, and stromal cell reprogramming, to bring about premetastatic niche formation and to determine metastatic organ tropism. There are a variety of oncogenic factors in tumor-derived sEVs that mediate cellular communication between local stromal cells and distal microenvironment, both of which are important in cancer progression and metastasis. Tumor-derived sEVs contain substances that are similar to parental tumor cells, and as such, sEVs could be biomarkers in cancer progression and potential therapeutic targets, particularly for predicting and preventing future metastatic development. Here, we review the mechanisms underlying the regulation by tumor-derived sEVs on cancer development and progression, including proliferation, metastasis, drug resistance, and immunosuppression, which coordinately shape the pro-metastatic microenvironment. In addition, we describe the application of sEVs to the development of cancer biomarkers and potential therapeutic modalities and discuss how they can be engineered and translated into clinical practice.
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Affiliation(s)
- Lingyun Feng
- Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Lijuan Guo
- Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Yoshimasa Tanaka
- Center for Medical Innovation, Nagasaki University, 1-7-1, Sakamoto, Nagasaki 852-8588, Japan
- Correspondence: (Y.T.); (L.S.); Tel.: +81-95-819-7063 (Y.T.); +86-27-8779-2024 (L.S.); Fax: +81-95-819-2189 (Y.T.); +86-27-8779-2072 (L.S.)
| | - Li Su
- Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
- Correspondence: (Y.T.); (L.S.); Tel.: +81-95-819-7063 (Y.T.); +86-27-8779-2024 (L.S.); Fax: +81-95-819-2189 (Y.T.); +86-27-8779-2072 (L.S.)
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14
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Duque G, Manterola C, Otzen T, Arias C, Palacios D, Mora M, Galindo B, Holguín JP, Albarracín L. Cancer Biomarkers in Liquid Biopsy for Early Detection of Breast
Cancer: A Systematic Review. Clin Med Insights Oncol 2022; 16:11795549221134831. [PMCID: PMC9634213 DOI: 10.1177/11795549221134831] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 10/10/2022] [Indexed: 11/05/2022] Open
Abstract
Background: Breast cancer (BC) is the most common neoplasm in women worldwide. Liquid
biopsy (LB) is a non-invasive diagnostic technique that allows the analysis
of biomarkers in different body fluids, particularly in peripheral blood and
also in urine, saliva, nipple discharge, volatile respiratory fluids, nasal
secretions, breast milk, and tears. The objective was to analyze the
available evidence related to the use of biomarkers obtained by LB for the
early diagnosis of BC. Methods: Articles related to the use of biomarkers for the early diagnosis of BC due
to LB, published between 2010 and 2022, from the databases (WoS, EMBASE,
PubMed, and SCOPUS) were included. The MInCir diagnostic scale was applied
in the articles to determine their methodological quality (MQ). Descriptive
statistics were used, as well as determination of weighted averages of each
variable, to analyze the extracted data. Sensitivity, specificity, and area
under the curve values for specific biomarkers (individual or in panels) are
described. Results: In this systematic review (SR), 136 articles met the selection criteria,
representing 17 709 patients with BC. However, 95.6% were case-control
studies. In 96.3% of cases, LB was performed in peripheral blood samples.
Most of the articles were based on microRNA (miRNA) analysis. The mean MQ
score was 25/45 points. Sensitivity, specificity, and area under the curve
values for specific biomarkers (individual or in panels) have been
found. Conclusions: The determination of biomarkers through LB is a useful mechanism for the
diagnosis of BC. The analysis of miRNA in peripheral blood is the most
studied methodology. Our results indicate that LB has a high sensitivity and
specificity for the diagnosis of BC, especially in early stages.
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Affiliation(s)
- Galo Duque
- Medical Sciences PhD Program,
Universidad de La Frontera, Temuco, Chile,Faculty of Medicine, Universidad del
Azuay, Cuenca, Ecuador,Galo Duque, Faculty of Medicine,
Universidad del Azuay. Postal address: Av. 24 de Mayo y Hernán Malo, Cuenca,
Ecuador 010107.
| | - Carlos Manterola
- Medical Sciences PhD Program,
Universidad de La Frontera, Temuco, Chile,Center of Excellence in Morphological
and Surgical Studies (CEMyQ), Universidad de La Frontera, Temuco, Chile
| | - Tamara Otzen
- Medical Sciences PhD Program,
Universidad de La Frontera, Temuco, Chile,Center of Excellence in Morphological
and Surgical Studies (CEMyQ), Universidad de La Frontera, Temuco, Chile
| | - Cristina Arias
- Faculty of Medicine, Universidad del
Azuay, Cuenca, Ecuador
| | | | - Miriann Mora
- Medical Sciences PhD Program,
Universidad de La Frontera, Temuco, Chile,Faculty of Medicine, Universidad del
Azuay, Cuenca, Ecuador
| | - Bryan Galindo
- Faculty of Medicine, Universidad del
Azuay, Cuenca, Ecuador
| | - Juan Pablo Holguín
- Medical Sciences PhD Program,
Universidad de La Frontera, Temuco, Chile,Faculty of Medicine, Universidad del
Azuay, Cuenca, Ecuador
| | - Lorena Albarracín
- Medical Sciences PhD Program,
Universidad de La Frontera, Temuco, Chile
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Ahmed R, Samanta S, Banerjee J, Kar SS, Dash SK. Modulatory role of miRNAs in thyroid and breast cancer progression and insights into their therapeutic manipulation. CURRENT RESEARCH IN PHARMACOLOGY AND DRUG DISCOVERY 2022; 3:100131. [PMID: 36568259 PMCID: PMC9780070 DOI: 10.1016/j.crphar.2022.100131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 08/22/2022] [Accepted: 09/25/2022] [Indexed: 11/07/2022] Open
Abstract
Over the past few decades, thyroid cancer has become one of the most common types of endocrine cancer, contributing to an increase in prevalence. In the year 2020, there were 586,202 newly diagnosed cases of thyroid cancer around the world. This constituted approximately 3.0% of all patients diagnosed with cancer. The World Health Organization reported that there will be 2.3 million women receiving treatment for breast cancer in 2020, with 685,000. Despite the fact that carcinoma is one of the world's leading causes of death, there is still a paucity of information about its biology. MicroRNAs (miRNAs; miRs) are non-coding RNAs that can reduce gene expression by cleaving the 3' untranslated regions of mRNA. These factors make them a potential protein translation inhibitor. Diverse biological mechanisms implicated in the genesis of cancer are modulated by miRNA. The investigation of global miRNA expression in cancer showed regulatory activity through up regulation and down-regulation in several cancers, including thyroid cancer and breast cancer. In thyroid cancer, miRNA influences several cancers related signaling pathways through modulating MAPK, PI3K, and the RAS pathway. In breast cancer, the regulatory activity of miRNA was played through the cyclin protein family, protein kinases and their inhibitors, and other growth promoters or suppressors, which modulated cell proliferation and cell cycle progression. This article's goal is to discuss key miRNA expressions that are involved in the development of thyroid and breast cancer as well as their therapeutic manipulation for these two specific cancer types.
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Affiliation(s)
- Rubai Ahmed
- Department of Physiology, University of Gour Banga, Malda, 732103, West Bengal, India
| | - Sovan Samanta
- Department of Physiology, University of Gour Banga, Malda, 732103, West Bengal, India
| | - Jhimli Banerjee
- Department of Physiology, University of Gour Banga, Malda, 732103, West Bengal, India
| | - Suvrendu Sankar Kar
- Department of Medicine, R.G.Kar Medical College and Hospital, Kolkata, 700004, West Bengal, India
| | - Sandeep Kumar Dash
- Department of Physiology, University of Gour Banga, Malda, 732103, West Bengal, India,Corresponding author.
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16
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Serum MicroRNAs: -28-3p, -31-5p, -378a-3p, and -382-5p as novel potential biomarkers in acute lymphoblastic leukemia. GENE REPORTS 2022. [DOI: 10.1016/j.genrep.2022.101582] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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17
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Yu B, Zhou S, Liang H, Ye Q, Wang Y. Development and Validation of a Novel Circulating miRNA-Based Diagnostic Score for Early Detection of Hepatocellular Carcinoma. Dig Dis Sci 2022; 67:2283-2292. [PMID: 33982217 DOI: 10.1007/s10620-021-07031-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 04/26/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND With the rise of liquid biopsy in oncology, circulating miRNAs have become one of the most promising noninvasive biomarkers for early detection of hepatocellular carcinoma (HCC). However, a reliable HCC-related circulating miRNA panel and corresponding diagnostic model remain to be explored. METHODS Five large public datasets related to intact miRNA profiles in the serum or tumors of HCC patients were included and divided into training cohorts (GSE113740 and TCGA-LIHC) and validation cohorts (GSE112264, GSE113486 and GSE106817). Compared with non-cancer controls and high-risk patients, key miRNAs dysregulated in both the serum and tumors of HCC patients were identified by differential expression analysis and overlapping analysis. The corresponding diagnostic model was constructed by LASSO logistic regression and evaluated by receiver operating characteristic curves and a nomogram with calibration plot. RESULTS A distinctive panel of HCC-related circulating miRNAs, including three upregulated miRNAs (miR-184, miR-532-5p, miR-221-3p) and three downregulated miRNAs (miR-5589-5p, let-7b-3p, miR-26b-3p), were rigorously screened out, all of which displayed significant discriminability between HCC patients and controls (all P < 0.05). In addition, a reliable six-circulating miRNA-based diagnostic score was constructed and displayed robust diagnostic ability for HCC (particularly for early-stage HCC) (AUC = 0.9535, P < 0.05) compared with that of the serum α-fetoprotein test. Importantly, its efficacy was sufficiently validated in three independent datasets (AUC = 0.9780/0.9961/0.9681, all P < 0.05). Furthermore, a visual nomogram based on the diagnostic score was correspondingly established to strengthen its clinical applicability. CONCLUSION The six-circulating miRNA-based diagnostic score may be a reliable noninvasive biomarker for early-stage HCC screening and dynamic monitoring of postoperative recurrence.
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Affiliation(s)
- Bin Yu
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei, 430071, People's Republic of China
| | - Shujun Zhou
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei, 430071, People's Republic of China
| | - Han Liang
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei, 430071, People's Republic of China
| | - Qifa Ye
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei, 430071, People's Republic of China.,The 3rd Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha, Hunan, 410013, People's Republic of China
| | - Yanfeng Wang
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei, 430071, People's Republic of China.
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18
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Valacchi G, Pambianchi E, Coco S, Pulliero A, Izzotti A. MicroRNA Alterations Induced in Human Skin by Diesel Fumes, Ozone, and UV Radiation. J Pers Med 2022; 12:176. [PMID: 35207665 PMCID: PMC8880698 DOI: 10.3390/jpm12020176] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 01/21/2022] [Accepted: 01/24/2022] [Indexed: 11/17/2022] Open
Abstract
Epigenetic alterations are a driving force of the carcinogenesis process. MicroRNAs play a role in silencing mutated oncogenes, thus defending the cell against the adverse consequences of genotoxic damages induced by environmental pollutants. These processes have been well investigated in lungs; however, although skin is directly exposed to a great variety of environmental pollutants, more research is needed to better understand the effect on cutaneous tissue. Therefore, we investigated microRNA alteration in human skin biopsies exposed to diesel fumes, ozone, and UV light for over 24 h of exposure. UV and ozone-induced microRNA alteration right after exposure, while the peak of their deregulations induced by diesel fumes was reached only at the end of the 24 h. Diesel fumes mainly altered microRNAs involved in the carcinogenesis process, ozone in apoptosis, and UV in DNA repair. Accordingly, each tested pollutant induced a specific pattern of microRNA alteration in skin related to the intrinsic mechanisms activated by the specific pollutant. These alterations, over a short time basis, reflect adaptive events aimed at defending the tissue against damages. Conversely, whenever environmental exposure lasts for a long time, the irreversible alteration of the microRNA machinery results in epigenetic damage contributing to the pathogenesis of inflammation, dysplasia, and cancer induced by environmental pollutants.
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Affiliation(s)
- Giuseppe Valacchi
- Animal Science Department, Plants for Human Health Institute, North Carolina State University, Research Campus Kannapolis, Kannapolis, NC 28081, USA; (G.V.); (E.P.)
- Department of Environmental Sciences and Prevention, University of Ferrara, 44121 Ferrara, Italy
- Department of Food and Nutrition, Kyung Hee University, Seoul 130-701, Korea
| | - Erika Pambianchi
- Animal Science Department, Plants for Human Health Institute, North Carolina State University, Research Campus Kannapolis, Kannapolis, NC 28081, USA; (G.V.); (E.P.)
| | - Simona Coco
- Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy;
| | | | - Alberto Izzotti
- Department of Experimental Medicine, University of Genova, 16132 Genova, Italy
- UOC Mutagenesis and Cancer Prevention, IRCCS San Martino Hospital, 16132 Genova, Italy
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19
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Ghafouri-Fard S, Khoshbakht T, Hussen BM, Taheri M, Samadian M. A Review on the Role of miR-1246 in the Pathoetiology of Different Cancers. Front Mol Biosci 2022; 8:771835. [PMID: 35047553 PMCID: PMC8762223 DOI: 10.3389/fmolb.2021.771835] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 11/22/2021] [Indexed: 01/22/2023] Open
Abstract
miR-1246 is a microRNA firstly recognized through application of a high throughput sequencing technique in human embryonic stem cells. Subsequent studies have shown the role of this microRNA in the carcinogenesis. miR-1246 has been found to exert oncogenic roles in colorectal, breast, renal, oral, laryngeal, pancreatic and ovarian cancers as well as melanoma and glioma. In lung, cervical and liver cancers, studies have reported contradictory results regarding the role of miR-1246. miR-1246 has been reported to regulate activity of RAF/MEK/ERK, GSK3β, Wnt/β-catenin, JAK/STAT, PI3K/AKT, THBS2/MMP and NOTCH2 pathways. In addition to affecting cell cycle progression and proliferation, miR-1246 can influence stemness and resistance of cancer cells to therapeutics. In the current review, we describe the summary of in vitro and in vivo studies about the influence of miR-1246 in carcinogenesis in addition to studies that measured expression levels of miR-1246 in clinical samples.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tayyebeh Khoshbakht
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bashdar Mahmud Hussen
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Iraq.,Center of Research and Strategic Studies, Lebanese French University, Erbil, Iraq
| | - Mohammad Taheri
- Institute of Human Genetics, Jena University Hospital, Jena, Germany
| | - Mohammad Samadian
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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20
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Jang JY, Ko EY, Jung JS, Kang KN, Kim YS, Kim CW. Evaluation of the Value of Multiplex MicroRNA Analysis as a Breast Cancer Screening in Korean Women under 50 Years of Age with a High Proportion of Dense Breasts. J Cancer Prev 2021; 26:258-265. [PMID: 35047452 PMCID: PMC8749312 DOI: 10.15430/jcp.2021.26.4.258] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/09/2021] [Accepted: 12/22/2021] [Indexed: 11/30/2022] Open
Abstract
This study was conducted to confirm the performance of the microRNA (miRNA) biomarker combination as a new breast cancer screening method in Korean women under the age of 50 with a high percentage of dense breasts. To determine the classification performance of a set of miRNA biomarkers (miR-1246, 202, 21, and 219B) useful for breast cancer screening, we determined whether there was a significant difference between the breast cancer and healthy control groups through box plots and the Mann–Whitney U-test, which was further examined in detail by age group. To verify the classification performance of the 4 miRNA biomarker set, 4 classification methods (logistic regression, random forest, XGBoost, and generalized linear model plus random forest) were applied, and 10-fold cross-validation was used as a validation method to improve performance stability. We confirmed that the best breast cancer detection performance was achievable in patients under 50 years of age when the set of 4 miRNAs were used. Under the age of 50, the 4 miRNA biomarkers showed the highest performance with a sensitivity of 85.29%, specificity of 93.33%, and area under the curve (AUC) of 0.961. Examining the results of 4 miRNA biomarkers was found to be an effective strategy for diagnosing breast cancer in Korean women under 50 years of age with dense breasts, and hence has the potential as a new breast cancer screening tool. Further validation in an appropriate screening population with large-scale clinical trials is required.
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21
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Dai YC, Pan Y, Quan MM, Chen Q, Pan Y, Ruan YY, Sun JG. MicroRNA-1246 Mediates Drug Resistance and Metastasis in Breast Cancer by Targeting NFE2L3. Front Oncol 2021; 11:677168. [PMID: 34926237 PMCID: PMC8671458 DOI: 10.3389/fonc.2021.677168] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Accepted: 11/16/2021] [Indexed: 12/16/2022] Open
Abstract
MicroRNA (miR)-1246 is abnormally expressed and has pro-oncogenic functions in multiple types of cancer. In the present study, its functions in breast cancer and the underlying mechanisms were further elucidated. The clinical relevance of miR-1246 was analyzed and its expression in clinical specimens and cell lines was examined by reverse transcription-quantitat000000ive PCR analysis. FACS was used to detect cell apoptosis and mitochondrial transmembrane potential. A Transwell system was used to detect cell migration and invasion. Luciferase assay was used to confirm the target gene of miR-1246. Xenograft and metastasis mouse models were constructed to determine the function of miR-1246 in vivo. miR-1246 was found to be negatively associated with overall survival in breast cancer. miR-1246 inhibitor could effectively increase the cytotoxicity of docetaxel (Doc) by inducing apoptosis, and impair cell migration and invasion by suppressing epithelial-to-mesenchymal transition. Nuclear factor (erythroid 2)-like factor 3 (NFE2L3) was confirmed as a new target gene of miR-1246, and its overexpression was shown to reduce drug resistance and migration of MDA-MB-231 cells. More importantly, NFE2L3-silencing attenuated the effect of miR-1246 inhibitor. Finally, the inhibition of miR-1246 effectively enhanced the cytotoxicity of Doc in xenografts and impaired breast cancer metastasis. Therefore, miR-1246 may promote drug resistance and metastasis in breast cancer by targeting NFE2L3.
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Affiliation(s)
- Yue-Chu Dai
- Department of Surgical Oncology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Yin Pan
- Department of Surgical Oncology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Ming-Ming Quan
- Department of Surgical Oncology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Qi Chen
- Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Yue Pan
- Department of Surgical Oncology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Yan-Yun Ruan
- Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Jian-Guo Sun
- Department of Surgical Oncology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China.,Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
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Prediction of Grade Reclassification of Prostate Cancer Patients on Active Surveillance through the Combination of a Three-miRNA Signature and Selected Clinical Variables. Cancers (Basel) 2021; 13:cancers13102433. [PMID: 34069838 PMCID: PMC8157371 DOI: 10.3390/cancers13102433] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 05/12/2021] [Accepted: 05/14/2021] [Indexed: 12/31/2022] Open
Abstract
Simple Summary Active surveillance (AS) has evolved as an alternative to radical treatment for potentially indolent prostate cancer. However, current selection criteria for entering AS are suboptimal, and a significant percentage of patients discontinue AS because of disease reclassification. Hence, there is an unmet need for novel biomarkers for the accurate identification of high-risk PCa and the unequivocal classification of indolent disease. Circulating biomarkers, including microRNAs identified through liquid biopsies, represent a valuable approach to improve on currently available clinicopathological risk-stratification tools. In an attempt to identify specific microRNA signatures as potential circulating biomarkers, the authors performed an unprecedented analysis of the global microRNA profile in plasma samples from AS patients and identified and validated a three-microRNA signature able to predict patient reclassification. The addition of the three-microRNA signature was able to improve the performance of currently available clinicopathological variables, thus showing potential for the refinement of AS patients’ selection. Abstract Active surveillance (AS) has evolved as a strategy alternative to radical treatments for very low risk and low-risk prostate cancer (PCa). However, current criteria for selecting AS patients are still suboptimal. Here, we performed an unprecedented analysis of the circulating miRNome to investigate whether specific miRNAs associated with disease reclassification can provide risk refinement to standard clinicopathological features for improving patient selection. The global miRNA expression profiles were assessed in plasma samples prospectively collected at baseline from 386 patients on AS included in three independent mono-institutional cohorts (training, testing and validation sets). A three-miRNA signature (miR-511-5p, miR-598-3p and miR-199a-5p) was found to predict reclassification in all patient cohorts (training set: AUC 0.74, 95% CI 0.60–0.87, testing set: AUC 0.65, 95% CI 0.51–0.80, validation set: AUC 0.68, 95% CI 0.56–0.80). Importantly, the addition of the three-miRNA signature improved the performance of the clinical model including clinicopathological variables only (AUC 0.70, 95% CI 0.61–0.78 vs. 0.76, 95% CI 0.68–0.84). Overall, we trained, tested and validated a three-miRNA signature which, combined with selected clinicopathological variables, may represent a promising biomarker to improve on currently available clinicopathological risk stratification tools for a better selection of truly indolent PCa patients suitable for AS.
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Tang LB, Ma SX, Chen ZH, Huang QY, Wu LY, Wang Y, Zhao RC, Xiong LX. Exosomal microRNAs: Pleiotropic Impacts on Breast Cancer Metastasis and Their Clinical Perspectives. BIOLOGY 2021; 10:biology10040307. [PMID: 33917233 PMCID: PMC8067993 DOI: 10.3390/biology10040307] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/28/2021] [Accepted: 04/03/2021] [Indexed: 01/07/2023]
Abstract
As a major threat factor for female health, breast cancer (BC) has garnered a lot of attention for its malignancy and diverse molecules participating in its carcinogenesis process. Among these complex carcinogenesis processes, cell proliferation, epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), and angiogenesis are the major causes for the occurrence of metastasis and chemoresistance which account for cancer malignancy. MicroRNAs packaged and secreted in exosomes are termed "exosomal microRNAs (miRNAs)". Nowadays, more researches have uncovered the roles of exosomal miRNAs played in BC metastasis. In this review, we recapitulated the dual actions of exosomal miRNAs exerted in the aggressiveness of BC by influencing migration, invasion, and distant metastasis. Next, we presented how exosomal miRNAs modify angiogenesis and stemness maintenance. Clinically, several exosomal miRNAs can govern the transformation between drug sensitivity and chemoresistance. Since the balance of the number and type of exosomal miRNAs is disturbed in pathological conditions, they are able to serve as instructive biomarkers for BC diagnosis and prognosis. More efforts are needed to connect the theoretical studies and clinical traits together. This review provides an outline of the pleiotropic impacts of exosomal miRNAs on BC metastasis and their clinical implications, paving the way for future personalized drugs.
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Affiliation(s)
- Li-Bo Tang
- Department of Pathophysiology, Basic Medical College, Nanchang University, Nanchang 330006, China; (L.-B.T.); (Q.-Y.H.); (L.-Y.W.); (Y.W.); (R.-C.Z.)
- Second Clinical Medical College, Nanchang University, Nanchang 330006, China;
| | - Shu-Xin Ma
- Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang 330006, China;
| | - Zhuo-Hui Chen
- Second Clinical Medical College, Nanchang University, Nanchang 330006, China;
| | - Qi-Yuan Huang
- Department of Pathophysiology, Basic Medical College, Nanchang University, Nanchang 330006, China; (L.-B.T.); (Q.-Y.H.); (L.-Y.W.); (Y.W.); (R.-C.Z.)
- Second Clinical Medical College, Nanchang University, Nanchang 330006, China;
| | - Long-Yuan Wu
- Department of Pathophysiology, Basic Medical College, Nanchang University, Nanchang 330006, China; (L.-B.T.); (Q.-Y.H.); (L.-Y.W.); (Y.W.); (R.-C.Z.)
- First Clinical Medical College, Nanchang University, Nanchang 330006, China
| | - Yi Wang
- Department of Pathophysiology, Basic Medical College, Nanchang University, Nanchang 330006, China; (L.-B.T.); (Q.-Y.H.); (L.-Y.W.); (Y.W.); (R.-C.Z.)
| | - Rui-Chen Zhao
- Department of Pathophysiology, Basic Medical College, Nanchang University, Nanchang 330006, China; (L.-B.T.); (Q.-Y.H.); (L.-Y.W.); (Y.W.); (R.-C.Z.)
- Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang 330006, China;
| | - Li-Xia Xiong
- Department of Pathophysiology, Basic Medical College, Nanchang University, Nanchang 330006, China; (L.-B.T.); (Q.-Y.H.); (L.-Y.W.); (Y.W.); (R.-C.Z.)
- Jiangxi Province Key Laboratory of Tumor Pathogenesis and Molecular Pathology, Nanchang 330006, China
- Correspondence: ; Tel.: +86-791-8636-0556
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Piombino C, Mastrolia I, Omarini C, Candini O, Dominici M, Piacentini F, Toss A. The Role of Exosomes in Breast Cancer Diagnosis. Biomedicines 2021; 9:biomedicines9030312. [PMID: 33803776 PMCID: PMC8003248 DOI: 10.3390/biomedicines9030312] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 03/13/2021] [Accepted: 03/16/2021] [Indexed: 12/15/2022] Open
Abstract
The importance of molecular re-characterization of metastatic disease with the purpose of monitoring tumor evolution has been acknowledged in numerous clinical guidelines for the management of advanced malignancies. In this context, an attractive alternative to overcome the limitations of repeated tissue sampling is represented by the analysis of peripheral blood samples as a 'liquid biopsy'. In recent years, liquid biopsies have been studied for the early diagnosis of cancer, the monitoring of tumor burden, tumor heterogeneity and the emergence of molecular resistance, along with the detection of minimal residual disease. Interestingly, liquid biopsy consents the analysis of circulating tumor cells, circulating tumor DNA and extracellular vesicles (EVs). In particular, EVs play a crucial role in cell communication, carrying transmembrane and nonmembrane proteins, as well as metabolites, lipids and nucleic acids. Of all EVs, exosomes mirror the biological fingerprints of the parental cells from which they originate, and therefore, are considered one of the most promising predictors of early cancer diagnosis and treatment response. The present review discusses current knowledge on the possible applications of exosomes in breast cancer (BC) diagnosis, with a focus on patients at higher risk.
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Affiliation(s)
- Claudia Piombino
- Department of Oncology and Hematology, Azienda Ospedaliero Universitaria di Modena, 41124 Modena, Italy; (C.P.); (C.O.); (M.D.); (F.P.)
| | - Ilenia Mastrolia
- Laboratory of Cellular Therapy, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy
- Correspondence: (I.M.); (A.T.)
| | - Claudia Omarini
- Department of Oncology and Hematology, Azienda Ospedaliero Universitaria di Modena, 41124 Modena, Italy; (C.P.); (C.O.); (M.D.); (F.P.)
| | | | - Massimo Dominici
- Department of Oncology and Hematology, Azienda Ospedaliero Universitaria di Modena, 41124 Modena, Italy; (C.P.); (C.O.); (M.D.); (F.P.)
- Laboratory of Cellular Therapy, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy
- Rigenerand srl, Medolla, 41036 Modena, Italy;
- Division of Oncology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy
| | - Federico Piacentini
- Department of Oncology and Hematology, Azienda Ospedaliero Universitaria di Modena, 41124 Modena, Italy; (C.P.); (C.O.); (M.D.); (F.P.)
- Division of Oncology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy
| | - Angela Toss
- Department of Oncology and Hematology, Azienda Ospedaliero Universitaria di Modena, 41124 Modena, Italy; (C.P.); (C.O.); (M.D.); (F.P.)
- Division of Oncology, Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy
- Correspondence: (I.M.); (A.T.)
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Jang JY, Kim YS, Kang KN, Kim KH, Park YJ, Kim CW. Multiple microRNAs as biomarkers for early breast cancer diagnosis. Mol Clin Oncol 2020; 14:31. [PMID: 33414912 PMCID: PMC7783718 DOI: 10.3892/mco.2020.2193] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 12/07/2020] [Indexed: 12/26/2022] Open
Abstract
MicroRNA (miRNA or miR) is stably present in plasma. It has been reported that miRNA could be used for detecting cancer. Circulating miRNAs are being increasingly recognized as powerful biomarkers in a number of different pathologies, including in breast cancer. The aim of the current study was to establish and validate miRNA sets that are useful for the early diagnosis of breast cancer. Specifically, the current study intended to determine whether miRNA biomarkers were tumor-specific and to statistically verify whether circulating miRNA analysis could be used for breast cancer diagnosis. In the present study, a total of nine candidate miRNA biomarkers were selected by examining reference miRNAs associated with the generation and progression of breast cancer to identify novel miRNAs that could be used to detect early breast cancer. A total of 226 plasma samples from patients with breast cancer were used. In addition, 146 plasma healthy samples were used as non-cancer controls. These samples were divided into training and validation cohorts. The training cohort was used to identify a combination of miRNA that could detect breast cancer. The validation cohort was used to validate this combination of miRNA. Total RNAs were isolated from collected samples. A total of 9 miRNAs were quantified using reverse-transcription quantitative PCR. A total of nine candidate miRNA expression levels were compared between patients with breast cancer and healthy controls. It was indicated that combinations of two or more of the nine miRNAs could detect breast cancer with higher accuracy than the use of a single biomarker. As a representative example, combinations of four miRNAs (miR-1246+miR-206+miR-24+miR-373) of the nine miRNAs had a sensitivity of 98%, a specificity of 96% and an accuracy of 97% for breast cancer detection in the validation cohort. The results of the present study suggest that multiple miRNAs could be used as potential biomarkers for early diagnosis of breast cancer. These biomarkers are expected to overcome limitations of mammography when used as an auxiliary diagnosis of mammography.
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Affiliation(s)
- Ji Young Jang
- BIOINFRA Life Science Inc., Jongno-gu, Seoul 03127, Republic of Korea
| | - Yeon Soo Kim
- DIOGENE Inc., Bundang-gu, Seongnam-Si 13486, Republic of Korea
| | - Kyung Nam Kang
- BIOINFRA Life Science Inc., Jongno-gu, Seoul 03127, Republic of Korea
| | - Kyo Hyun Kim
- DIOGENE Inc., Bundang-gu, Seongnam-Si 13486, Republic of Korea
| | - Yu Jin Park
- BIOINFRA Life Science Inc., Jongno-gu, Seoul 03127, Republic of Korea
| | - Chul Woo Kim
- BIOINFRA Life Science Inc., Jongno-gu, Seoul 03127, Republic of Korea
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Li K, Chen Y. CYP2C8 regulated by GAS5/miR-382-3p exerts anti-cancerous properties in liver cancer. Cancer Biol Ther 2020; 21:1145-1153. [PMID: 33180658 DOI: 10.1080/15384047.2020.1840886] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
A cornucopia of literatures has characterized the involvement of a host of functional molecules in liver cancer. Herein, according to online datasets, we found that cytochrome P450 family 2 subfamily C member 8 (CYP2C8) was downregulated in liver cancer, and high CYP2C8 expression was associated with favorable overall survival. Lower levels of CYP2C8 were confirmed in liver cancer cells. CYP2C8 overexpression efficiently attenuated liver cancer cell proliferation and promoted apoptosis. We then discovered that miR-382-3p directly targeted CYP2C8 to inhibit its expression in liver cancer cells based on bioinformatic prediction and experimental confirmation. Moreover, a cytoplasmic long noncoding RNA (lncRNA), growth arrest-specific 5 (GAS5), sponged and down-regulated miR-382-3p, thus positively modulating CYP2C8 expression. Rescue assays indicated that GAS5 overexpression gave rise to decreased proliferation and increased apoptosis of liver cancer cells, while CYP2C8 knockdown counteracted GAS5-mediated anti-carcinogenic effects. In summary, our work offered a solid experimental foundation for understanding the functional role of CYP2C8 and the mechanism of GAS5/miR-382-3p/CYP2C8 axis in cell proliferation and apoptosis of liver cancer.
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Affiliation(s)
- Kezhi Li
- Department of General Surgery, The First People's Hospital of Qujing , Qujing, People's Republic of China
| | - Yonglun Chen
- Department of Anesthesiology, The First People's Hospital of Qujing , Qujing, People's Republic of China
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27
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Beylerli O, Beeraka NM, Gareev I, Pavlov V, Yang G, Liang Y, Aliev G. MiRNAs as Noninvasive Biomarkers and Therapeutic Agents of Pituitary Adenomas. Int J Mol Sci 2020; 21:E7287. [PMID: 33023145 PMCID: PMC7583927 DOI: 10.3390/ijms21197287] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Revised: 09/19/2020] [Accepted: 09/20/2020] [Indexed: 12/14/2022] Open
Abstract
Pituitary adenoma (PA) accounts for 10-15% of all intracranial neoplasms. Even though most pituitary adenomas are benign, it is known that almost 35% of them exhibit an aggressive clinical course, including rapid proliferative activity and invasion of neighboring tissues. MicroRNAs (miRNAs) are short single-stranded RNA molecules that can influence post-transcriptional regulation by controlling target genes. Based on research data on miRNAs over the past 20 years, more than 60% of genes encoding human proteins are regulated by miRNAs, which ultimately control basic cellular mechanisms, including cell proliferation, differentiation, and apoptosis. Dysregulation of miRNAs has been observed in a number of diseases, especially tumors like PA. A majority of miRNAs are expressed within the cells themselves. However, the circulating miRNAs can be detected in several biological fluids of the human body. The identification of circulating miRNAs as new molecular markers may increase the ability to detect a tumor, predict the course of a disease, plan to choose suitable treatment, and diagnose at the earliest signs of impending neoplastic transformation. Therapy of PAs with aggressive behavior is a complex task. When surgery and chemotherapy fail, radiotherapy becomes the treatment of choice against PAs. Therefore, the possibility of implementing circulating miRNAs as innovative diagnostic and therapeutic agents for PA is one of the main exciting ideas.
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Affiliation(s)
- Ozal Beylerli
- Central Research Laboratory, Bashkir State Medical University, 450008 Ufa, Republic of Bashkortostan, Russia; (O.B.); (I.G.); (V.P.)
| | - Narasimha M. Beeraka
- Department of Biochemistry, JSS Academy of Higher Education & Research, CEMR lab, DST-FIST Supported Department and Center, Mysuru 570015, Karnataka, India;
| | - Ilgiz Gareev
- Central Research Laboratory, Bashkir State Medical University, 450008 Ufa, Republic of Bashkortostan, Russia; (O.B.); (I.G.); (V.P.)
| | - Valentin Pavlov
- Central Research Laboratory, Bashkir State Medical University, 450008 Ufa, Republic of Bashkortostan, Russia; (O.B.); (I.G.); (V.P.)
| | - Guang Yang
- Department of Neurosurgery, the First Affiliated Harbin Medical University, Harbin 150001, China;
- Institute of Brain Science, Harbin Medical University, Harbin 150001, China
| | - Yanchao Liang
- Department of Neurosurgery, the First Affiliated Harbin Medical University, Harbin 150001, China;
- Institute of Brain Science, Harbin Medical University, Harbin 150001, China
| | - Gjumrakch Aliev
- Sechenov First Moscow State Medical University Sechenov University, 119146 Moscow, Russia
- Research Institute of Human Morphology, Russian Academy of Medical Science, 117418 Moscow, Russia
- Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, 142432 Moscow, Russia
- GALLY International Research Institute, 7733 Louis Pasteur Drive, #330, San Antonio, TX 78229, USA
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Identification of miRNA signatures in serum exosomes as a potential biomarker after radiotherapy treatment in glioma patients. Ann Diagn Pathol 2019; 44:151436. [PMID: 31865249 DOI: 10.1016/j.anndiagpath.2019.151436] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 12/05/2019] [Indexed: 12/14/2022]
Abstract
Despite development in therapies, the high recurrence and low positivity of biomarkers for diagnosis still result in glioma with high mortality. In this study, we aimed to identify a potential miRNA signature to evaluate the effect of radiotherapy in glioma patients. MicroRNA (miRNA) sequencing was performed on miRNAs isolated from serum exosomes in a cohort of glioma patients before and after radiotherapy. A total of 18 up-regulated differentially expressed (DE) miRNAs and 16 down-regulated DE miRNAs were identified. Subsequently, the target genes of DE miRNAs were predicted based on multiple miRNA-target databases. Further, it was indicated that these targets were primarily involved in metabolic process, p53 signaling pathway and cancer pathways, suggesting that these miRNAs play a crucial role in glioma by regulating targets and affect the occurrence and development of the disease. In general, this study presented the variation of miRNAs in blood exosomes before and after radiotherapy. It can not only be helpful for the diagnosis of glioma, but also find new candidate biomarkers for monitoring the condition and evaluating the efficacy of radiotherapy in glioma. It provides a new idea for the diagnosis, treatment and prognosis evaluation of glioma.
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29
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Chen X, Wu RZ, Ren ZM, Tong YL, Chen S, Yang F, Dai GH. Regulation of microRNAs by rape bee pollen on benign prostate hyperplasia in rats. Andrologia 2019; 52:e13386. [PMID: 31733069 DOI: 10.1111/and.13386] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 07/11/2019] [Accepted: 07/15/2019] [Indexed: 01/08/2023] Open
Abstract
The miRNAs are dysregulated in BPH. Rape bee pollen (RBP) is used to improve benign prostatic hyperplasia (BPH). Whether RBP treats BPH by regulating the dysregulated miRNAs remains unclear. Here, we identified miRNAs regulated along with the improvement of BPH by RBP in posterior lobes of prostate in rats. Firstly, to screened miRNAs might relate to improvement of BPH by RBP, we compared differentially expressed miRNAs between BPH model group and RBP group by high-throughput sequencing. As a result, 10 known miRNAs and 17 novel miRNA were up-regulated in RBP group, and 6 known and 13 novel miRNAs were down-regulated. Secondly, among the known miRNAs, we identified those that might relate to BPH by RT-qPCR, while only rno-miR-184 was screened, so we compared it among normal control group, BPH model group and RBP group. The results showed that rno-miR-184 was significantly lower expressed in BPH group, but up-regulated along with the improvement of BPH by RBP. Moreover, expression level of rno-miR-184 was no difference between RBP group and normal control level. Therefore, we considered that RBP might improve BPH through regulating expression of miRNAs like rno-miR-184 in prostate in rats.
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Affiliation(s)
- Xuan Chen
- Institute of Basic Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Ren-Zhao Wu
- Institute of Basic Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Ze-Ming Ren
- Institute of Basic Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Ye-Ling Tong
- Institute of Basic Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Sisi Chen
- Institute of Basic Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Feng Yang
- Institute of Basic Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Guan-Hai Dai
- Institute of Basic Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
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Liu F, Zhang Q, Liang Y. MicroRNA-598 acts as an inhibitor in retinoblastoma through targeting E2F1 and regulating AKT pathway. J Cell Biochem 2019; 121:2294-2302. [PMID: 31674056 DOI: 10.1002/jcb.29453] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Accepted: 10/10/2019] [Indexed: 12/17/2022]
Abstract
Recently, microRNAs (miRNAs) receive more attention due to their role in the pathogenesis of malignancies. Retinoblastoma (RB) is the most serious and harmful malignant tumor in infants and young children with eye diseases, which often endangers the lives of children. This study was designed to determine how miR-598 is involved in RB progression. In this study, quantitative reverse transcription-polymerase chain reaction, Western blot, dual-luciferase reporter, Cell Counting Kit-8, and Transwell assays were adopted to detect miR-598 expression and function in RB. The decreased expression of miR-598 was identified in RB. Overexpression of miR-598 suppressed the viability and metastasis of RB cells. Further, E2F transcription factor 1 (E2F1) is verified as a direct target of miR-598. Furthermore, E2F1 recovered miR-598-mediated-inhibition of cell viability and metastasis in RB. In addition, miR-598 was found to promote cell apoptosis and inactivate the protein kinase B (AKT) pathway in RB. miR-598 suppressed RB cell viability and metastasis through inhibiting E2F1 and inactivating AKT pathway, which may provide a new perspective for RB treatment.
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Affiliation(s)
- Fengge Liu
- Department of Ophthalmology, Zoucheng People's Hospital, Zoucheng, Shandong, China
| | - Qi Zhang
- Department of Ophthalmology, LinQing People's Hospital, Linqing, Shandong, China
| | - Yan Liang
- Department of Ophthalmology, Qingdao University Medical College Affiliated Yantai Yuhuangding Hospital, Yantai, Shandong, China
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Bottani M, Banfi G, Lombardi G. Circulating miRNAs as Diagnostic and Prognostic Biomarkers in Common Solid Tumors: Focus on Lung, Breast, Prostate Cancers, and Osteosarcoma. J Clin Med 2019; 8:E1661. [PMID: 31614612 PMCID: PMC6833074 DOI: 10.3390/jcm8101661] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 10/04/2019] [Accepted: 10/06/2019] [Indexed: 12/22/2022] Open
Abstract
An early cancer diagnosis is essential to treat and manage patients, but it is difficult to achieve this goal due to the still too low specificity and sensitivity of classical methods (imaging, actual biomarkers), together with the high invasiveness of tissue biopsies. The discovery of novel, reliable, and easily collectable cancer markers is a topic of interest, with human biofluids, especially blood, as important sources of minimal invasive biomarkers such as circulating microRNAs (miRNAs), the most promising. MiRNAs are small non-coding RNAs and known epigenetic modulators of gene expression, with specific roles in cancer development/progression, which are next to be implemented in the clinical routine as biomarkers for early diagnosis and the efficient monitoring of tumor progression and treatment response. Unfortunately, several issues regarding their validation process are still to be resolved. In this review, updated findings specifically focused on the clinical relevance of circulating miRNAs as prognostic and diagnostic biomarkers for the most prevalent cancer types (breast, lung, and prostate cancers in adults, and osteosarcoma in children) are described. In addition, deep analysis of pre-analytical, analytical, and post-analytical issues still affecting the circulation of miRNAs' validation process and routine implementation is included.
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Affiliation(s)
- Michela Bottani
- IRCCS Istituto Ortopedico Galeazzi, Laboratory of Experimental Biochemistry and Molecular Biology, Via Riccardo Galeazzi 4, 20161 Milano, Italy.
| | - Giuseppe Banfi
- IRCCS Istituto Ortopedico Galeazzi, Laboratory of Experimental Biochemistry and Molecular Biology, Via Riccardo Galeazzi 4, 20161 Milano, Italy.
- Vita-Salute San Raffaele University, 20132 Milano, Italy.
| | - Giovanni Lombardi
- IRCCS Istituto Ortopedico Galeazzi, Laboratory of Experimental Biochemistry and Molecular Biology, Via Riccardo Galeazzi 4, 20161 Milano, Italy.
- Dept. of Physiology and Pharmacology, Gdańsk University of Physical Education and Sport, Gdańsk, ul. Kazimierza Górskiego 1, 80-336 Pomorskie, Poland.
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Ma Y, Yan F, Wei W, Deng J, Li L, Liu L, Sun J. MicroRNA-598 inhibits the growth and maintenance of gastric cancer stem-like cells by down-regulating RRS1. Cell Cycle 2019; 18:2757-2769. [PMID: 31438772 DOI: 10.1080/15384101.2019.1657338] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Emerging evidence has identified the critical role of microRNAs in gastric cancer (GC). Herein, this study intends to characterize the tumor suppressive role of microRNA-598 (miR-598) in GC stem-like cells, with the involvement of RRS1. The CD133+ GC stem-like cells were sorted by flow cytometry, after which immunofluorescence assay was used to determine the co-localization of CD133 and CD44v8-10. The miR-598 expression was examined in the CD133+ and CD133- cells. Subsequently, the CD133+ cells were subjected to miR-598 mimics, miR-598 inhibitors or RRS1 siRNA to validate the effect of miR-598 on GC stem-like cell proliferation, colony formation, apoptosis, migration and invasion capacities. Besides, the effect of miR-598 on the expression of key factors (OCT4, SOX2 and NANOG) associated with stem cell characteristics was measured. The obtained results indicated that the sphere forming capacity was higher in CD133+ cells. CD133+ MKN-45 cells expressed CD133 and CD44v8-10, and were expressed on the cell membrane. MiR-598 was poorly expressed in CD133+ cells. Notably, miR-598 negatively regulated RRS1. In response to miR-598 mimics and RRS1 siRNA, the MKN-45 cells displayed inhibited proliferation, colony formation, migration and invasion, accompanied by elevated apoptosis. Besides, the miR-598 inhibitors reversed the situation. This study highlights that miR-598 a tumor suppressor in GC stem-like cells by inhibiting RRS1, whereby miR-598 represses MKN-45 cell growth and invasion by attenuating self-renewal of GC stem-like cells.
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Affiliation(s)
- Yanling Ma
- Department of Oncology, Hubei No.3 People's Hospital of Jianghan University , Wuhan , China
| | - Fei Yan
- Department of Oncology, Hubei No.3 People's Hospital of Jianghan University , Wuhan , China
| | - Wujie Wei
- Department of Oncology, Hubei No.3 People's Hospital of Jianghan University , Wuhan , China
| | - Jie Deng
- Department of Oncology, Hubei No.3 People's Hospital of Jianghan University , Wuhan , China
| | - Li Li
- Department of Oncology, Hubei No.3 People's Hospital of Jianghan University , Wuhan , China
| | - Li Liu
- Department of Oncology, Hubei No.3 People's Hospital of Jianghan University , Wuhan , China
| | - Jianhai Sun
- Department of Oncology, Hubei No.3 People's Hospital of Jianghan University , Wuhan , China
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MiR-382 functions as tumor suppressor and chemosensitizer in colorectal cancer. Biosci Rep 2019; 39:BSR20180441. [PMID: 29700213 PMCID: PMC6689104 DOI: 10.1042/bsr20180441] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 04/21/2018] [Accepted: 04/24/2018] [Indexed: 12/24/2022] Open
Abstract
Increasing evidence suggests that microRNAs (miRNAs) play a critical role in tumorigenesis. Decreased expression of miR-382 has been observed in various types of cancers. However, the biological function of miR-382 in colorectal cancer (CRC) is still largely unknown. Here, we found that miR-382 was down-regulated in human colorectal cancer tissues and cell lines associated with it. MiR-382 inhibited colorectal cancer cell proliferation, migration, invasion, and enhance chemosensitivity. Furthermore, we identified Krüppel-like factor 12 (KLF12) and homeodomain-interacting protein kinase 3 (HIPK3) as the target of miR-382, and miR-382 rescued the promotion effect of KFL12 on migration and enhanced chemosensitivity in colorectal cancer cell lines. Collectively, these findings revealed that miR-382 inhibits migration and enhances chemosensitivity by targeting KLF12 and HIPK3 in colorectal cancer. These findings might serve as a tumor suppressor in CRC.
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Xie C, Huang T, Teng Z, Xu S, Bu J, Li M, Zhang Y, Zhang J. A meta-analysis of the diagnostic value of microRNA-1246 for malignant tumors. Medicine (Baltimore) 2019; 98:e15848. [PMID: 31145333 PMCID: PMC6708943 DOI: 10.1097/md.0000000000015848] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Cancer morbidity and mortality are growing rapidly worldwide. There have been an increasing number of studies on the correlation between miRNA1246 expression in circulating blood and tumors; however, no comprehensive conclusion has been reached. Therefore, this meta-analysis was carried out to systematically evaluate the diagnostic value of blood levels of microRNA-1246 for malignant tumors. METHODS We searched PubMed, MEDLINE, Embase, The Cochrane Library, the China National Knowledge Internet (CNKI), and Wanfang databases from the inception of each database until November 2018. The quality of the included literature was evaluated using the quality assessment tool called Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The data were pooled using Stata14 and Meta-DiSc 1.4 software. RESULTS Seven studies were included. The pooled sensitivity (SENS) was 0.80 (95% CI 0.65-0.89), the pooled specificity (SPEC) was 0.77 (95% CI 0.70-0.83), the pooled positive likelihood ratio (PLR) was 3.55 (95% CI 2.53-4.99), the pooled negative likelihood ratio (NLR) was 0.26 (95% CI 0.16-0.47), the pooled diagnostic odds ratio (DOR) was 13.78 (95% CI 5.84-32.5), and the area under the curve (AUC) was 0.83 (95% CI 0.79-0.86). The result of Deeks' funnel plot was P = 0.31, indicating a lack of publication bias. CONCLUSION MicroRNA-1246 in the blood can be used as a good indicator for the diagnosis of malignant tumor diseases and has a moderate diagnostic accuracy for the differentiation of patients with malignant tumors from healthy people.
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Affiliation(s)
- Chunlin Xie
- Department of Thoracic Surgery, The 1st Affiliated Hospital of Kunming Medical University, Kunming
| | - Tao Huang
- Department of Thoracic Surgery, The 1st Affiliated Hospital of Kunming Medical University, Kunming
| | - Zhaowei Teng
- Department of Orthopaedics, The 6th Affiliated Hospital of Kunming Medical University, Yuxi
| | - Shuanglan Xu
- Department of Respiratory Medicine, The Fourth Affiliated Hospital of Kunming Medical University, The Second People's Hospital of Yunnan Province, Kunming, Yunnan, PR China
| | - Junhui Bu
- Department of Thoracic Surgery, The 1st Affiliated Hospital of Kunming Medical University, Kunming
| | - Mengzhou Li
- Department of Thoracic Surgery, The 1st Affiliated Hospital of Kunming Medical University, Kunming
| | - Yibing Zhang
- Department of Thoracic Surgery, The 1st Affiliated Hospital of Kunming Medical University, Kunming
| | - Jing Zhang
- Department of Thoracic Surgery, The 1st Affiliated Hospital of Kunming Medical University, Kunming
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Xing F, Wang S, Zhou J. The Expression of MicroRNA-598 Inhibits Ovarian Cancer Cell Proliferation and Metastasis by Targeting URI. MOLECULAR THERAPY-ONCOLYTICS 2018; 12:9-15. [PMID: 30662936 PMCID: PMC6325085 DOI: 10.1016/j.omto.2018.12.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Accepted: 12/02/2018] [Indexed: 11/17/2022]
Abstract
Unconventional prefoldin RPB5 interactor (URI, or RMP, a member of the prefoldin family of molecular chaperones) exhibits oncogenic activity in several types of cancer, including ovarian cancer. However, the underlying regulatory mechanism in ovarian cancer remains unclear. MicroRNAs (miRNAs) negatively regulate gene expression, and their dysregulation has been implicated in tumorigenesis. To elucidate the role of miRNAs in URI-induced ovarian cancer, miR-598 and URI were overexpressed in the SKOV3 ovarian cancer cell line. The CCK8 kit was used to determine cell proliferation, and the Transwell assay was used to measure cell invasion and migration. RT-PCR and western blotting were used to analyze the expression of miR-598 and URI, and the luciferase reporter assay was used to examine the interaction between miR-598 and URI. Nude mice were used to characterize the regulation of tumor growth in vivo. The results showed that the expression of miR-598 inhibited the proliferation, invasion, and migration of ovarian cancer cells by targeting URI. The inhibitory effect of miR-598 was reversed by overexpression of URI. The luciferase reporter assay showed that miR-598 downregulated URI by directly targeting the 3′ UTR of URI. In vivo studies showed that the expression of miR-598 significantly inhibited the growth of tumors. Taken together, the results suggested that miR-598 inhibited tumor growth and metastasis by targeting URI.
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Affiliation(s)
- Feng Xing
- Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital of Tongji University, Tongji University School of Medicine, No. 301 Middle Yan Chang Road, Shanghai, 200072, China
| | - Shuo Wang
- Department of Ultrasound, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Jianhong Zhou
- Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital of Tongji University, Tongji University School of Medicine, No. 301 Middle Yan Chang Road, Shanghai, 200072, China
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Identification of micro-RNA expression profile related to recurrence in women with ESMO low-risk endometrial cancer. J Transl Med 2018; 16:131. [PMID: 29783999 PMCID: PMC5963057 DOI: 10.1186/s12967-018-1515-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Accepted: 05/12/2018] [Indexed: 12/15/2022] Open
Abstract
Background Actual European pathological classification of early-stage endometrial cancer (EC) may show insufficient accuracy to precisely stratify recurrence risk, leading to potential over or under treatment. Micro-RNAs are post-transcriptional regulators involved in carcinogenic mechanisms, with some micro-RNA patterns of expression associated with EC characteristics and prognosis. We previously demonstrated that downregulation of micro-RNA-184 was associated with lymph node involvement in low-risk EC (LREC). The aim of this study was to evaluate whether micro-RNA signature in tumor tissues from LREC women can be correlated with the occurrence of recurrences. Methods MicroRNA expression was assessed by chip analysis and qRT-PCR in 7 formalin-fixed paraffin-embedded (FFPE) LREC primary tumors from women whose follow up showed recurrences (R+) and in 14 FFPE LREC primary tumors from women whose follow up did not show any recurrence (R−), matched for grade and age. Various statistical analyses, including enrichment analysis and a minimum p-value approach, were performed. Results The expression levels of micro-RNAs-184, -497-5p, and -196b-3p were significantly lower in R+ compared to R− women. Women with a micro-RNA-184 fold change < 0.083 were more likely to show recurrence (n = 6; 66%) compared to those with a micro-RNA-184 fold change > 0.083 (n = 1; 8%), p = 0.016. Women with a micro-RNA-196 fold change < 0.56 were more likely to show recurrence (n = 5; 100%) compared to those with a micro-RNA-196 fold change > 0.56 (n = 2; 13%), p = 0.001. Conclusions These findings confirm the great interest of micro-RNA-184 as a prognostic tool to improve the management of LREC women.
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Bermisheva MA, Takhirova ZR, Gilyazova IR, Khusnutdinova EK. MicroRNA Biogenesis Pathway Gene Polymorphisms Are Associated with Breast Cancer Risk. RUSS J GENET+ 2018. [DOI: 10.1134/s1022795418040051] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Bott A, Erdem N, Lerrer S, Hotz-Wagenblatt A, Breunig C, Abnaof K, Wörner A, Wilhelm H, Münstermann E, Ben-Baruch A, Wiemann S. miRNA-1246 induces pro-inflammatory responses in mesenchymal stem/stromal cells by regulating PKA and PP2A. Oncotarget 2018; 8:43897-43914. [PMID: 28159925 PMCID: PMC5546423 DOI: 10.18632/oncotarget.14915] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Accepted: 12/26/2016] [Indexed: 12/20/2022] Open
Abstract
The tumor microenvironment (TME) has an impact on breast cancer progression by creating a pro-inflammatory milieu within the tumor. However, little is known about the roles of miRNAs in cells of the TME during this process. We identified six putative oncomiRs in a breast cancer dataset, all strongly correlating with poor overall patient survival. Out of the six candidates, miR-1246 was upregulated in aggressive breast cancer subtypes and expressed at highest levels in mesenchymal stem/stroma cells (MSCs). Functionally, miR-1246 led to a p65-dependent increase in transcription and release of pro-inflammatory mediators IL-6, CCL2 and CCL5 in MSCs, and increased NF-κB activity. The pro-inflammatory phenotype of miR-1246 in MSCs was independent of TNFα stimulations and mediated by direct targeting of the tumor-suppressors PRKAR1A and PPP2CB. In vitro recapitulation of the TME revealed increased Stat3 phosphorylation in breast epithelial (MCF10A) and cancer cells (SK-BR-3, MCF7, T47D) upon incubation with conditioned medium (CM) of MSCs overexpressing miR-1246. Additionally, this stimulation enhanced proliferation of MCF10A cells, increased migration of MDA-MB-231 cells and induced attraction of THP-1 monocytic cells. Our data shows that miR-1246 acts as both key-enhancer of pro-inflammatory responses in MSCs and putative oncomiR in breast cancer, suggesting its influence on cancer-related inflammation and breast cancer progression.
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Affiliation(s)
- Alexander Bott
- Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Nese Erdem
- Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Shalom Lerrer
- Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv, Israel
| | - Agnes Hotz-Wagenblatt
- Bioinformatics Group, Genomics & Proteomics Core Facility (GPCF), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Christian Breunig
- Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Khalid Abnaof
- Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Angelika Wörner
- Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Heike Wilhelm
- Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Ewald Münstermann
- Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Adit Ben-Baruch
- Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv, Israel
| | - Stefan Wiemann
- Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Heydari N, Nikbakhsh N, Sadeghi F, Farnoush N, Khafri S, Bastami M, Parsian H. Overexpression of serum MicroRNA-140-3p in premenopausal women with newly diagnosed breast cancer. Gene 2018; 655:25-29. [PMID: 29474861 DOI: 10.1016/j.gene.2018.02.032] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Revised: 01/16/2018] [Accepted: 02/12/2018] [Indexed: 12/21/2022]
Abstract
AIMS The purpose of the present study was to evaluate microRNA-140-3p expression level in breast cancer patients in comparison to healthy controls. PATIENTS & METHODS Serum microRNA-140-3p level was quantified by realtime quantitative reverse transcription PCR in 40 women with breast cancer and 40 healthy subjects. RESULTS Serum microRNA-140-3p level in patients compared to healthy subjects was significantly up-regulated (P = 0.01). MicroRNA-140-3p had a good diagnostic accuracy for discrimination of the two groups (AUC = 0.667; sensitivity = 70%; specificity = 50%). Serum microRNA-140-3p level was overexpressed in premenopausal patients who were ≤48 years old. ROC curve showed a similar pattern again (AUC = 0.690; sensitivity = 73%; specificity = 50%). CONCLUSIONS microRNA-140-3p has the potential for detection of breast cancer, especially in premenopausal and in ≤48 years old women.
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Affiliation(s)
- Nadia Heydari
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Novin Nikbakhsh
- Cancer Research Center, Babol University of Medical Sciences, Babol, Iran
| | - Farzin Sadeghi
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Nazila Farnoush
- Department of Surgery, Babol University of Medical Sciences, Babol, Iran
| | - Soraya Khafri
- Department of Epidemiology, Babol University of Medical Sciences, Babol, Iran
| | - Milad Bastami
- Department of Medical Genetics, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hadi Parsian
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
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40
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Xiong J, Xiong K, Bing Z. Clinical and RNA expression integrated signature for urothelial bladder cancer prognosis. Cancer Biomark 2018; 21:535-546. [DOI: 10.3233/cbm-170314] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- Jie Xiong
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
| | - Ke Xiong
- School of Medicine, Tongji University, Shanghai, China
| | - Zhitong Bing
- Department of Computational Physics, Institute of Modern Physics of Chinese Academy of Sciences, Lanzhou, Gansu, China
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41
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Netz U, Carter J, Eichenberger MR, Feagins K, Galbraith NJ, Dryden GW, Pan J, Rai SN, Galandiuk S. Plasma microRNA Profile Differentiates Crohn's Colitis From Ulcerative Colitis. Inflamm Bowel Dis 2018; 24:159-165. [PMID: 29272478 PMCID: PMC5858028 DOI: 10.1093/ibd/izx009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is commonly divided into 2 entities: Crohn's disease (CD) and ulcerative colitis (UC). Differentiating between these entities when dealing with IBD confined to the colon is important, especially when planning surgical treatment. Due to ambiguous histological or endoscopic findings, accurate diagnosis is not possible in up to 15% of cases. The aim of this study was to determine whether plasma microRNAs (miRNAs) can help differentiate Crohn's colitis (CC) from ulcerative colitis. METHODS Patients with isolated CC and with UC were enrolled in our study from January 2010 to May 2016. Peripheral blood was collected, and total RNA was isolated from plasma. Screening was performed for 380 common miRNAs. miRNAs that were differentially expressed between these 2 groups were chosen, and their differential expression was confirmed using single miRNA assays in a larger sample size. A predictive model was generated using these data. Significantly differentially expressed miRNAs were then validated utilizing the predictive model to assess blinded data from the single assays. RESULTS Screening was performed on 8 patients from each group. Seven differentially expressed miRNAs were chosen for single assay confirmation. Two miRNAs (miR-598, miR-642) were consistently different between the patient groups (P = 0.013, P = 0.005). Using blinded data, these 2 miRNAs were validated using the predictive model, achieving an overall accuracy of 75% (95% confidence interval, 40.7-92.9). CONCLUSIONS We identified 2 plasma miRNAs that differentiated CC from UC. Our data indicate the promise and feasibility of a plasma miRNA-based assay to distinguish between these 2 conditions.
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Affiliation(s)
- Uri Netz
- Price Institute of Surgical Research, The Hiram C. Polk Jr., MD Department of
Surgery, University of Louisville, Louisville, Kentucky,Department of Surgery A, Soroka University Medical Center, Beer Sheva,
Israel,Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva,
Israel
| | - Jane Carter
- Price Institute of Surgical Research, The Hiram C. Polk Jr., MD Department of
Surgery, University of Louisville, Louisville, Kentucky
| | - M Robert Eichenberger
- Price Institute of Surgical Research, The Hiram C. Polk Jr., MD Department of
Surgery, University of Louisville, Louisville, Kentucky
| | - Kayla Feagins
- Price Institute of Surgical Research, The Hiram C. Polk Jr., MD Department of
Surgery, University of Louisville, Louisville, Kentucky
| | - Norman J Galbraith
- Price Institute of Surgical Research, The Hiram C. Polk Jr., MD Department of
Surgery, University of Louisville, Louisville, Kentucky
| | - Gerald W Dryden
- Department of Medicine, Division of Gastroenterology, Hepatology, and
Nutrition University of Louisville School of Medicine Louisville, Kentucky
| | - Jianmin Pan
- Department of Bioinformatics and Biostatistics, University of Louisville
School of Public Health and Information Sciences, Louisville, Kentucky
| | - Shesh N Rai
- Department of Bioinformatics and Biostatistics, University of Louisville
School of Public Health and Information Sciences, Louisville, Kentucky
| | - Susan Galandiuk
- Price Institute of Surgical Research, The Hiram C. Polk Jr., MD Department of
Surgery, University of Louisville, Louisville, Kentucky,Address correspondence to: Susan Galandiuk, MD, FACG, AGAF, The Hiram C.
Polk Jr, MD Department of Surgery, 550 South Jackson Street, Louisville, KY 40202 (e-mail:
)
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Bulkowska M, Rybicka A, Senses KM, Ulewicz K, Witt K, Szymanska J, Taciak B, Klopfleisch R, Hellmén E, Dolka I, Gure AO, Mucha J, Mikow M, Gizinski S, Krol M. MicroRNA expression patterns in canine mammary cancer show significant differences between metastatic and non-metastatic tumours. BMC Cancer 2017; 17:728. [PMID: 29115935 PMCID: PMC5678797 DOI: 10.1186/s12885-017-3751-1] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2016] [Accepted: 11/01/2017] [Indexed: 01/12/2023] Open
Abstract
Background MicroRNAs may act as oncogenes or tumour suppressor genes, which make these small molecules potential diagnostic/prognostic factors and targets for anticancer therapies. Several common oncogenic microRNAs have been found for canine mammary cancer and human breast cancer. On account of this, large-scale profiling of microRNA expression in canine mammary cancer seems to be important for both dogs and humans. Methods Expression profiles of 317 microRNAs in 146 canine mammary tumours of different histological type, malignancy grade and clinical history (presence/absence of metastases) and in 25 control samples were evaluated. The profiling was performed using microarrays. Significance Analysis of Microarrays test was applied in the analysis of microarray data (both unsupervised and supervised data analyses were performed). Validation of the obtained results was performed using real-time qPCR. Subsequently, predicted targets for the microRNAs were searched for in miRBase. Results Results of the unsupervised analysis indicate that the primary factor separating the samples is the metastasis status. Predicted targets for microRNAs differentially expressed in the metastatic vs. non-metastatic group are mostly engaged in cell cycle regulation, cell differentiation and DNA-damage repair. On the other hand, the supervised analysis reveals clusters of differentially expressed microRNAs unique for the tumour type, malignancy grade and metastasis factor. Conclusions The most significant difference in microRNA expression was observed between the metastatic and non-metastatic group, which suggests a more important role of microRNAs in the metastasis process than in the malignant transformation. Moreover, the differentially expressed microRNAs constitute potential metastasis markers. However, validation of cfa-miR-144, cfa-miR-32 and cfa-miR-374a levels in blood samples did not follow changes observed in the non-metastatic and metastatic tumours. Electronic supplementary material The online version of this article (10.1186/s12885-017-3751-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Malgorzata Bulkowska
- Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776, Warsaw, Poland
| | - Agata Rybicka
- Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776, Warsaw, Poland
| | - Kerem Mert Senses
- Department of Molecular Biology and Genetics, Faculty of Science, SB Building, Bilkent University, 06800, Ankara, Turkey
| | - Katarzyna Ulewicz
- Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776, Warsaw, Poland
| | - Katarzyna Witt
- Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776, Warsaw, Poland
| | - Joanna Szymanska
- Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776, Warsaw, Poland
| | - Bartlomiej Taciak
- Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776, Warsaw, Poland
| | - Robert Klopfleisch
- Institute of Veterinary Pathology, Freie Universitaet Berlin, Robert-von-Ostertag-Strasse 15, Building 31, 14163, Berlin, Germany
| | - Eva Hellmén
- Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Box 7011, 75007, Uppsala, Sweden
| | - Izabella Dolka
- Department of Pathology and Veterinary Diagnostics, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776, Warsaw, Poland
| | - Ali O Gure
- Department of Molecular Biology and Genetics, Faculty of Science, SB Building, Bilkent University, 06800, Ankara, Turkey
| | - Joanna Mucha
- Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776, Warsaw, Poland
| | - Mariusz Mikow
- Veterinary Clinic 'Elwet', Niepodleglosci 24/30, 02-653 Warsaw, Poland
| | - Slawomir Gizinski
- Department of Large Animal Diseases with Clinic, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 100, 02-797, Warsaw, Poland
| | - Magdalena Krol
- Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776, Warsaw, Poland.
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Cell transfer of information via miR-loaded exosomes: a biophysical approach. EUROPEAN BIOPHYSICS JOURNAL: EBJ 2017; 46:803-811. [PMID: 29043382 DOI: 10.1007/s00249-017-1262-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Revised: 09/14/2017] [Accepted: 10/09/2017] [Indexed: 01/08/2023]
Abstract
A new communication route among cells was reported in recent years, via extracellular vesicles and their cargo. Exosomes in particular are attracting increasing interest as privileged mediators of this cell communication route. The exosome-mediated transfer of nucleic acids, especially of microRNAs, is particularly promising for their use both as biomarkers of pathologies and as a therapeutic tool. Here, a simplified model of interaction among cells, microRNAs and vesicles is studied using a biophysical approach. A synthetic and fluorescent microRNA (i.e. miR-1246 conjugated with TAMRA) was selected to model cell communication, monitoring its internalization in cells. The fluorescent miR-1246, either naked or included in synthetic or natural vesicles, was incubated with human breast adenocarcinoma cells (MCF7) for different times. A comparison between this human microRNA and its DNA copy or an exogenous microRNA (from Caenorhabditis elegans) allowed assessment of the specificity of the information transfer through microRNAs, and especially associated with exosomes. The uptake of naked miR-1246 was indeed higher both in terms of number of targeted cells and intensity of fluorescence signal with respect to the other nucleic acids tested. The same occurred with miR-1246 loaded exosomes, evidencing a specific uptake only partially due to the lipidic components and present only when the human microRNA was loaded in exosomes, which were themselves derived from the same MCF7 cells.
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Exosomal MicroRNAs in Breast Cancer towards Diagnostic and Therapeutic Applications. Cancers (Basel) 2017; 9:cancers9070071. [PMID: 28672799 PMCID: PMC5532607 DOI: 10.3390/cancers9070071] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2017] [Revised: 06/16/2017] [Accepted: 06/16/2017] [Indexed: 12/21/2022] Open
Abstract
Soon after the discovery of microRNAs over 15 years ago, a myriad of research groups around the world sought to develop clinical applications in breast cancer for these short, noncoding, regulatory RNAs. While little of this knowledge has translated into the clinic, the recent research explosion on cell-to-cell communication via exosomes and other extracellular vesicles has rekindled interest in microRNA-based clinical applications. microRNAs appear to be a preferential and important cargo of exosomes in mediating biological effects in recipient cells. This review highlights recent studies on the biology of exosomal microRNAs (exo-miRNAs) and discusses potential clinical applications. From a diagnostic perspective, circulating exo-miRNAs may represent breast cancer cell content and/or tumor microenvironmental reactions to cancer cell growth. Thus, serum or plasma analysis of exo-miRNAs could be useful for early disease detection or for monitoring treatment response and disease progression. From a therapeutic perspective, exo-miRNAs derived from different cell types have been implicated in supporting or restraining tumor growth, conferring drug resistance, and preparing the metastatic niche. Strategies to interfere with the loading or delivery of tumor-promoting exo-miRNAs or to replenish tumor-suppressive miRNAs via exosomal delivery are under investigation. These recent studies provide new hope and opportunities, but study design limitations and technical challenges will need to be overcome before seriously considering clinical application of exo-miRNAs.
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Feng J, Qi B, Guo L, Chen LY, Wei XF, Liu YZ, Zhao BS. miR-382 functions as a tumor suppressor against esophageal squamous cell carcinoma. World J Gastroenterol 2017; 23:4243-4251. [PMID: 28694664 PMCID: PMC5483498 DOI: 10.3748/wjg.v23.i23.4243] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2017] [Revised: 03/14/2017] [Accepted: 03/31/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To explore the effect of miR-382 on esophageal squamous cell carcinoma (ESCC) in vitro and its possible molecular mechanism.
METHODS Eca109 cells derived from human ESCC and Het-1A cells derived from human normal esophageal epithelium were used. Lentivirus-mediated miR-382 was overexpressed in Eca109 cells. The effect of miR-382 on cell proliferation was evaluated by MTT and colony formation assay. For cell cycle analysis, cells were fixed and stained for 30 min with propidium iodide (PI) staining buffer containing 10 mg/mL PI and 100 mg/mL RNase A, and analyzed by BD FACSCalibur™ flow cytometer. For cell apoptosis assay, cells were stained with an Annexin V-FITC/PI Apoptosis Detection Kit according to the manufacturer’s instructions and analyzed by a dual-laser flow cytometer. Cell invasion and migration abilities were determined through use of transwell chambers, non-coated or pre-coated with matrigel. Levels of proteins related to cell growth and migration were examined by western blotting.
RESULTS Endogenous miR-382 was down-regulated in Eca109 cells compared with Het-1A. Introduction of miR-382 not only significantly inhibited proliferation and colony formation, but also arrested cell cycle at the G2/M phase, as well as promoted apoptosis and autophagy in Eca109 cells. Migration, invasion and epithelial-mesenchymal transition of Eca109 cells were suppressed by overexpressing miR-382. Western blotting results showed that miR-382 inhibited the phosphorylation of mTOR and 4E-BP1.
CONCLUSION miR-382 functions as a tumor suppressor against ESCC development and metastasis, and could be considered as a potential drug source for the treatment of ESCC patients.
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陈 帅, 周 永, 陈 颖, 陈 小, 李 光, 杨 加, 雷 玉, 赵 光, 黄 秋, 杨 长, 杜 亚, 黄 云. [Specific microRNA expression profiles of lung adenocarcinoma in Xuanwei region and bioinformatic analysis for predicting their target genes and related signaling pathways]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2016; 37:238-244. [PMID: 28219870 PMCID: PMC6779667 DOI: 10.3969/j.issn.1673-4254.2017.02.16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 09/17/2016] [Indexed: 06/06/2023]
Abstract
OBJECTIVE To identify differentially expressed microRNAs (miRNAs) related to lung adenocarcinoma in Xuanwei region and predict their target genes and related signaling pathways based on bioinformatic analysis. METHODS High-throughput microarray assay was performed to detect miRNA expression profiles in 34 paired human lung adenocarcinoma and adjacent normal tissues (including 24 cases in Xuanwei region and 10 in other regions). Gene ontology and KEGG pathway analyses were used to predict the target genes and the regulatory signaling pathways. RESULTS Thirty-four miRNAs were differentially expressed in lung adenocarcinoma tissues in cases in Xuanwei region as compared with cases in other regions, including 23 upregulated and 11 downregulated miRNAs. The predicted target genes included GF, RTK, SOS, IRS1, BCAP, CYTOKINSR, ECM, ITGB, FAK and Gbeta;Y involving the PI3K/Alt, WNT and MAPK pathways. CONCLUSION The specific microRNA expression profiles of lung adenocarcinoma in cases found in Xuanwei region allow for a better understanding of the pathogenesis of lung adenocarcinoma in Xuanwei. The predicted target genes may involve the PI3K/Alt, WNT and MAPK pathways.
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Affiliation(s)
- 帅 陈
- />昆明医科大学第三附属医院//云南省肿瘤医院//云南省肺癌研究重点实验室，云南 昆明 650000Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University/ Tumor Hospital of Yunnan Province/ Yunnan Key Laboratory of Lung Cancer Research, Kunming 650000, China
| | - 永春 周
- />昆明医科大学第三附属医院//云南省肿瘤医院//云南省肺癌研究重点实验室，云南 昆明 650000Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University/ Tumor Hospital of Yunnan Province/ Yunnan Key Laboratory of Lung Cancer Research, Kunming 650000, China
| | - 颖 陈
- />昆明医科大学第三附属医院//云南省肿瘤医院//云南省肺癌研究重点实验室，云南 昆明 650000Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University/ Tumor Hospital of Yunnan Province/ Yunnan Key Laboratory of Lung Cancer Research, Kunming 650000, China
| | - 小波 陈
- />昆明医科大学第三附属医院//云南省肿瘤医院//云南省肺癌研究重点实验室，云南 昆明 650000Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University/ Tumor Hospital of Yunnan Province/ Yunnan Key Laboratory of Lung Cancer Research, Kunming 650000, China
| | - 光剑 李
- />昆明医科大学第三附属医院//云南省肿瘤医院//云南省肺癌研究重点实验室，云南 昆明 650000Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University/ Tumor Hospital of Yunnan Province/ Yunnan Key Laboratory of Lung Cancer Research, Kunming 650000, China
| | - 加鹏 杨
- />昆明医科大学第三附属医院//云南省肿瘤医院//云南省肺癌研究重点实验室，云南 昆明 650000Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University/ Tumor Hospital of Yunnan Province/ Yunnan Key Laboratory of Lung Cancer Research, Kunming 650000, China
| | - 玉洁 雷
- />昆明医科大学第三附属医院//云南省肿瘤医院//云南省肺癌研究重点实验室，云南 昆明 650000Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University/ Tumor Hospital of Yunnan Province/ Yunnan Key Laboratory of Lung Cancer Research, Kunming 650000, China
| | - 光强 赵
- />昆明医科大学第三附属医院//云南省肿瘤医院//云南省肺癌研究重点实验室，云南 昆明 650000Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University/ Tumor Hospital of Yunnan Province/ Yunnan Key Laboratory of Lung Cancer Research, Kunming 650000, China
| | - 秋博 黄
- />昆明医科大学第三附属医院//云南省肿瘤医院//云南省肺癌研究重点实验室，云南 昆明 650000Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University/ Tumor Hospital of Yunnan Province/ Yunnan Key Laboratory of Lung Cancer Research, Kunming 650000, China
| | - 长绍 杨
- />昆明医科大学第三附属医院//云南省肿瘤医院//云南省肺癌研究重点实验室，云南 昆明 650000Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University/ Tumor Hospital of Yunnan Province/ Yunnan Key Laboratory of Lung Cancer Research, Kunming 650000, China
| | - 亚茜 杜
- />昆明医科大学第三附属医院//云南省肿瘤医院//云南省肺癌研究重点实验室，云南 昆明 650000Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University/ Tumor Hospital of Yunnan Province/ Yunnan Key Laboratory of Lung Cancer Research, Kunming 650000, China
| | - 云超 黄
- />昆明医科大学第三附属医院//云南省肿瘤医院//云南省肺癌研究重点实验室，云南 昆明 650000Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University/ Tumor Hospital of Yunnan Province/ Yunnan Key Laboratory of Lung Cancer Research, Kunming 650000, China
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