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1
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Sun Q, Lei X, Yang X. The crosstalk between non-coding RNAs and oxidative stress in cancer progression. Genes Dis 2025; 12:101286. [PMID: 40028033 PMCID: PMC11870203 DOI: 10.1016/j.gendis.2024.101286] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 02/07/2024] [Accepted: 02/21/2024] [Indexed: 03/05/2025] Open
Abstract
As living standards elevate, cancers are appearing in growing numbers among younger individuals globally and these risks escalate with advancing years. One of the reasons is that instability in the cancer genome reduces the effectiveness of conventional drug treatments and chemotherapy, compared with more targeted therapies. Previous research has discovered non-coding RNAs' crucial role in shaping genetic networks involved in cancer cell growth and invasion through their influence on messenger RNA production or protein binding. Additionally, the interaction between non-coding RNAs and oxidative stress, a crucial process in cancer advancement, cannot be overlooked. Essentially, oxidative stress results from the negative effects of radicals within the body and ties directly to cancer gene expression and signaling. Therefore, this review focuses on the mechanism between non-coding RNAs and oxidative stress in cancer progression, which is conducive to finding new cancer treatment strategies.
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Affiliation(s)
- Qiqi Sun
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Xiaoyong Lei
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Xiaoyan Yang
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
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2
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Jeong SJ, Lee KH, Cho JY. Comparative epigenomics to clinical trials in human breast cancer and canine mammary tumor. Anim Cells Syst (Seoul) 2025; 29:12-30. [PMID: 40115961 PMCID: PMC11924266 DOI: 10.1080/19768354.2025.2477024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 02/09/2025] [Accepted: 02/12/2025] [Indexed: 03/23/2025] Open
Abstract
Epigenetics and epigenomics are captivating fields of molecular biology, dedicated to the exploration of heritable alterations in gene expression and cellular phenotypes, which transpire devoid of any discernible modifications to the fundamental DNA sequence. This intricate regulatory apparatus encompasses multiple mechanisms, prominently featuring DNA methylation, histone modifications, and the involvement of non-coding RNA molecules in pivotal roles. To achieve a comprehensive grasp of these diverse mechanisms, it is imperative to conduct research employing animal models as proxies for human studies. Since experimental animal models like mice and rats struggle to replicate the diverse environmental conditions experienced by humans, this review focuses on comparing common epigenetic alterations in naturally occurring tumors in canine models, which share the human environment, with those in humans. Through this, we emphasize the importance of an epigenetic regulation in the comparative medical approach to a deeper understanding of cancers and further development of cancer treatments. Additionally, we elucidate epigenetic modifications pertinent to specific developmental stages, the ageing process, and the progression of various diseases.
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Affiliation(s)
- Su-Jin Jeong
- Department of Biochemistry, College of Veterinary Medicine, Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Science, Seoul National University, Seoul, Republic of Korea
- Comparative Medicine Disease Research Center, Seoul National University, Seoul, Republic of Korea
| | - Kang-Hoon Lee
- Department of Biochemistry, College of Veterinary Medicine, Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Science, Seoul National University, Seoul, Republic of Korea
- Comparative Medicine Disease Research Center, Seoul National University, Seoul, Republic of Korea
| | - Je-Yoel Cho
- Department of Biochemistry, College of Veterinary Medicine, Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Science, Seoul National University, Seoul, Republic of Korea
- Comparative Medicine Disease Research Center, Seoul National University, Seoul, Republic of Korea
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3
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Prasad M, Hamsa D, Fareed M, Karobari MI. An update on the molecular mechanisms underlying the progression of miR-21 in oral cancer. World J Surg Oncol 2025; 23:73. [PMID: 40025548 PMCID: PMC11871704 DOI: 10.1186/s12957-025-03732-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Accepted: 02/26/2025] [Indexed: 03/04/2025] Open
Abstract
Globally, oral cancer ranks among the top ten cancers, with a higher prevalence in lower-income countries, where risk factors such as tobacco use, excessive alcohol consumption, and poor oral hygiene are widespread. Metastasis plays a critical role in cancer progression. miR-21 is a crucial regulator of cancer metastasis, profoundly influencing cellular and molecular pathways that contribute to tumour aggressiveness. As a microRNA, miR-21 downregulates tumour suppressor genes, promoting cell proliferation, survival, invasion, and migration. Its role in epithelial-mesenchymal transition (EMT) further facilitates metastatic behaviour. miR-21 also modulates the tumour microenvironment by promoting angiogenesis and altering immune responses, thus enhancing cancer progression.Moreover, miRNA - 21 influences the various signalling pathways like PI3K/ AKT, TGF-β, NF-κB, and STAT3, as well as involved in the cell fate mechanisms known as Autophagy and apoptosis. Clinically, elevated miR-21 levels are associated with poor prognosis, advanced tumour stages, and decreased survival rates, making it a valuable prognostic marker. Additionally, miR-21 expression levels can predict resistance to chemotherapy and targeted therapies, aiding in personalized treatment planning. Therapeutically, targeting miR-21 through anti-miR-21 oligonucleotides, small molecule inhibitors, and miRNA sponges shows promise in pre-clinical studies, potentially inhibiting tumour growth and improving sensitivity to existing treatments. Overall, miR-21's multifaceted role in cancer biology, its prognostic and predictive value, and its potential as a therapeutic target highlight its significance in advancing cancer diagnosis, treatment, and patient outcomes. Further research and clinical trials are essential to exploit miR-21's capabilities in oncology fully.
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Affiliation(s)
- Monisha Prasad
- Center for Global Health Research, Saveetha Institute of Medical and Technical Sciences, Saveetha Medical College and Hospitals, Saveetha University, Chennai, 602105, India
| | - D Hamsa
- Department of Biochemistry, JKK Munirajah College of Agricultural Science, TN Palayam, Erode, India
| | - Mohammad Fareed
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Kingdom of Saudi Arabia, P.O. Box: 71666, 11597, Diriyah, Riyadh, Saudi Arabia
| | - Mohmed Isaqail Karobari
- Department of Conservative Dentistry and Endodontics, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600077, Tamil Nadu, India.
- Department of Conservative Dentistry and Endodontics, Faculty of Dentistry, University of Puthisastra, Phnom Penh, 12211, Cambodia.
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Verma A, Patel K, Kumar A. Targeting drug resistance in breast cancer: the potential of miRNA and nanotechnology-driven delivery systems. NANOSCALE ADVANCES 2024:d4na00660g. [PMID: 39569336 PMCID: PMC11575621 DOI: 10.1039/d4na00660g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 11/11/2024] [Indexed: 11/22/2024]
Abstract
Breast cancer is the second leading cause of cancer-related deaths in females worldwide. Despite significant advancements in treatment, drug resistance remains a major challenge, limiting the effectiveness of therapies and leading to dismal outcomes. Approximately 50% of HER2+ breast cancer patients develop resistance to trastuzumab, and patients with triple-negative breast cancer often experience resistance to first-line therapies. The drug resistance mechanisms involve altered drug uptake, enhanced DNA repair, and dysregulated apoptosis pathways. MicroRNAs are essential in regulating cellular processes involved in both homeostasis and disease. Recent data suggest that microRNAs can overcome drug resistance by regulating the pathways that confer drug resistance. Combining different conventional anticancer agents with microRNA therapies holds promise for enhancing treatment effectiveness against drug resistant breast cancer. Advancements in nano-drug delivery systems have facilitated the effective delivery of microRNAs by improving their stability, targeting specific cells, and enhancing cellular uptake. This review elucidates the recent advancements in microRNA-based therapies, their effects on gene expression, and their clinical efficacy in overcoming drug resistance in breast cancer.
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Affiliation(s)
- Aditi Verma
- Biological and Life Sciences, School of Arts & Sciences, Ahmedabad University Central Campus, Navrangpura Ahmedabad 380009 Gujarat India
| | - Krunal Patel
- Biological and Life Sciences, School of Arts & Sciences, Ahmedabad University Central Campus, Navrangpura Ahmedabad 380009 Gujarat India
| | - Ashutosh Kumar
- Biological and Life Sciences, School of Arts & Sciences, Ahmedabad University Central Campus, Navrangpura Ahmedabad 380009 Gujarat India
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Koopaie M, Akhbari P, Fatahzadeh M, Kolahdooz S. Identification of common salivary miRNA in oral lichen planus and oral squamous cell carcinoma: systematic review and meta-analysis. BMC Oral Health 2024; 24:1177. [PMID: 39367474 PMCID: PMC11452954 DOI: 10.1186/s12903-024-04986-0] [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: 02/24/2024] [Accepted: 10/01/2024] [Indexed: 10/06/2024] Open
Abstract
BACKGROUND Oral lichen planus (OLP) is a chronic inflammatory condition that can impact patients' quality of life. While its exact etiology remains unclear, it is associated with an increased risk of malignant transformation. Currently, the diagnosis of OLP relies on clinical examination and histopathological analysis, which can be invasive. Therefore, there is an urgent need for non-invasive and accurate diagnostic biomarkers. This systematic review and meta-analysis aims to investigate the potential of salivary microRNAs as promising candidates for OLP diagnosis. This meta-analysis seeks to identify specific microRNAs that are differentially expressed and could serve as reliable biomarkers for OLP diagnosis. METHODS Our strategy involved searching for pertinent keywords in multiple academic databases including Cochrane Library, Embase, LIVIVO, MEDLINE, Ovid, ProQuest, Scopus, Web of Science, Espacenet, and Google Scholar search engine. Upon identification, articles were screened and data extracted from the eligible studies. Split component synthesis method was utilized to assess specificity, sensitivity, likelihood and diagnostic odds ratios. The random-effects meta-analysis approach was used to combine study findings and develop pooled diagnostic performance metrics. Hierarchical summary receiver operating characteristic (ROC) plots were generated to determine area under the curve. Subgroup analyses concerning the type of saliva and control groups were also performed. RESULTS Among the fourteen studies included in our systematic review, five were eligible for meta-analysis. Salivary microRNAs showed the pooled sensitivity of 0.80 (95% Confidence Interval (95% CI): 0.68-0.88), specificity of 0.89 (95% CI: 0.82-0.94), diagnostic odds ratio of 28.45 (95% CI: 10.40-77.80), and area under the curve (AUC) of 0.93 for OLP diagnosis. Unstimulated saliva had higher sensitivity and specificity than oral swirl samples as the biomarker medium for OLP diagnosis. Meta-analysis uncovered that miR-27a, miR-137, miR-1290, miR-27b, miR-4484, miR-142, and miR-1246 had the highest diagnostic odds ratio for OLP. CONCLUSIONS Our systematic review and meta-analysis demonstrate that salivary microRNAs can serve as valuable biomarkers for the diagnosis of OLP. The findings highlight the exceptional accuracy of salivary microRNAs in differentiating OLP patients from healthy controls and assessing the risk of malignant transformation.
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Affiliation(s)
- Maryam Koopaie
- Department of Oral Medicine, School of Dentistry, Tehran University of Medical Sciences, North Kargar St, P.O. BOX: 14395-433, Tehran, 14399-55991, Iran.
| | - Parisa Akhbari
- Department of Oral Medicine, School of Dentistry, Tehran University of Medical Sciences, North Kargar St, P.O. BOX: 14395-433, Tehran, 14399-55991, Iran
| | - Mahnaz Fatahzadeh
- Division of Oral Medicine, Department of Oral Medicine, Rutgers School of Dental Medicine, 110 Bergen Street, Newark, NJ, 07103, USA
| | - Sajad Kolahdooz
- Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences, Tehran, Iran
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6
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Suzuki T, Nakanishi Y, Tanino T, Nishimaki-Watanabe H, Kobayashi H, Ohni S, Tang X, Hakamada K, Masuda S. Immunohistochemical and molecular profiles of heterogeneous components of metaplastic breast cancer: a squamous cell carcinomatous component was distinct from a spindle cell carcinomatous component. Discov Oncol 2024; 15:95. [PMID: 38564036 PMCID: PMC10987432 DOI: 10.1007/s12672-024-00950-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 03/22/2024] [Indexed: 04/04/2024] Open
Abstract
Metaplastic breast carcinoma (MBC), a category of breast cancer, includes different histological types, which are occasionally mixed and heterogeneous. Considering the heterogeneity of cancer cells in a tumour mass has become highly significant, not only from a biological aspect but also for clinical management of recurrence. This study aimed to analyse the immunohistochemical and molecular profiles of each MBC component of a tumour mass. Twenty-five MBC tumours were histologically evaluated, and the most frequent MBC component (c) was squamous cell carcinoma (SCC), followed by spindle cell carcinoma (SpCC). A total of 69 components of MBC and non-MBC in formalin-fixed paraffin-embedded sections were examined for 7 markers by immunohistochemistry. SCC(c) were significantly PTEN negative and CK14 positive, and SpCC(c) were significantly E-cadherin negative and vimentin positive. Multivariate analyses revealed that immunohistochemical profiles of normal/intraductal (IC)(c), no special type (NST)(c), and MBC(c) differed; moreover, SCC(c) and SpCC(c) were distinctly grouped. PTEN gene mutation was detected only in SCC(c) (2/7), but not in SpCC(c). Next-generation sequence analyses for 2 cases with tumours containing SCC(c) demonstrated that PTEN gene mutation increased progressively from IC(c) to NST(c) to SCC(c). In conclusion, the immunohistochemical and molecular profiles of the SCC(c) of MBC are distinct from those of the SpCC(c).
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Affiliation(s)
- Takahiro Suzuki
- Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, Japan
| | - Yoko Nakanishi
- Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan
| | - Tomoyuki Tanino
- Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan
| | - Haruna Nishimaki-Watanabe
- Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan
| | - Hiroko Kobayashi
- Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan
| | - Sumie Ohni
- Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan
| | - Xiaoyan Tang
- Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan
| | - Kenichi Hakamada
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, Japan
| | - Shinobu Masuda
- Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, Japan.
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7
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Yasothkumar D, Ramani P, Jayaraman S, Ramalingam K, Tilakaratne WM. Expression Profile of Circulating Exosomal microRNAs in Leukoplakia, Oral Submucous Fibrosis, and Combined Lesions of Leukoplakia and Oral Submucous Fibrosis. Head Neck Pathol 2024; 18:28. [PMID: 38536520 PMCID: PMC10973321 DOI: 10.1007/s12105-024-01627-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 02/11/2024] [Indexed: 01/11/2025]
Abstract
OBJECTIVES This study aims to elucidate the expression of circulating exosomal miRNAs miRNA 21, miRNA 184, and miRNA 145 in the studied groups, including patients with (i) leukoplakia; (ii) oral submucous fibrosis; (iii) oral submucous fibrosis with leukoplakia; (iv) oral squamous cell carcinoma; and (v) healthy individuals. STUDY DESIGN An observational study was conducted among 54 patients who reported to the outpatient department of Saveetha Dental College and Hospitals. The patients were divided into three groups: Group I healthy individuals (n = 18), Group II: case group (leukoplakia, OSMF, and leukoplakia and OSMF) (n = 18), and Group III: OSCC (n = 18). Real-time polymerase chain reaction analysis was carried out to assess the expression profiles of miRNA 21, miRNA 184, and miRNA 145. The statistical analysis was calculated using SPSS software version 23. RESULTS All three miRNAs showed a statistically significant difference in the one-way ANOVA test between the case group (leukoplakia, OSMF, and leukoplakia and OSMF), healthy group, and OSCC group (p < 0.005). The case group (leukoplakia, OSMF, leukoplakia and OSMF) showed upregulated expression of miRNA 21 and miRNA 184 with threefold change and fourfold change and downregulated expression of miRNA 145 with 1.5-fold change when compared to apparently healthy individuals. CONCLUSION Plasma circulating exosomal miRNAs miRNA 21, miRNA 145, and miRNA 184 expression could be a novel panel of plasma biomarkers to categorise case group (leukoplakia, OSMF, leukoplakia and OSMF) patients with a high risk of malignant transformation.
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Affiliation(s)
- Dinesh Yasothkumar
- Department of Oral and Maxillofacial Pathology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, India.
| | - Pratibha Ramani
- Department of Oral and Maxillofacial Pathology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, India
| | - Selvaraj Jayaraman
- Department of Biochemistry, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, India
| | - Karthikeyan Ramalingam
- Department of Oral and Maxillofacial Pathology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, India
| | - W M Tilakaratne
- Department of Oral & Maxillofacial Clinical Sciences, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur, Malaysia
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8
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Lee SH, Brianna. Association of microRNA-21 expression with breast cancer subtypes and its potential as an early biomarker. Pathol Res Pract 2024; 254:155073. [PMID: 38218039 DOI: 10.1016/j.prp.2023.155073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 12/29/2023] [Indexed: 01/15/2024]
Abstract
Breast cancer has become the most diagnosed cancer worldwide in 2020 with high morbidity and mortality rates. The alarming increase in breast cancer incidence has sprung many researchers to focus on developing novel screening tests to identify early breast cancer which will allow clinicians to provide timely and effective treatments. With much evidence supporting the notion that the deregulation of miRNAs (a class of non-coding RNA) greatly contributes to cancer initiation and progression, the promising role of miRNAs as cancer biomarkers is gaining traction in the research world. Among the upregulated miRNAs identified in breast carcinogenesis, miR-21 was shown to be significantly expressed in breast cancer tissues and bodily fluids of breast cancer patients. Therein, this review paper aims to provide an overview of breast cancer, the role and significance of miR-21 in breast cancer pathogenesis, and its potential as a breast cancer biomarker. The paper also discusses the current types of tumor biomarkers and their limitations, the presence of miR-21 in extracellular vesicles and plasma, screening methods available for miRNA detection along with some challenges faced in developing diagnostic miR-21 testing for breast cancer to provide readers with a comprehensive outlook based on using miR-21 in clinical settings.
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Affiliation(s)
- Sau Har Lee
- School of Biosciences, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya 47500, Malaysia; Digital Health and Medical Advancements Impact Lab, Taylor's University, Subang Jaya 47500, Malaysia.
| | - Brianna
- Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Jalan Universiti, Bandar Sunway, Darul Ehsan, Selangor 47500, Malaysia
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9
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Mohammadi M, Fazilat A, Mamalo AS, Ojarudi M, Hemmati-Dinarvand M, Beilankouhi EAV, Valilo M. Correlation of PTEN signaling pathway and miRNA in breast cancer. Mol Biol Rep 2024; 51:221. [PMID: 38281224 DOI: 10.1007/s11033-023-09191-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Accepted: 12/21/2023] [Indexed: 01/30/2024]
Abstract
Breast cancer (BC) is one of the most common cancers among women and can be fatal if not diagnosed and treated on time. Various genetic and environmental factors play a significant role in the development and progression of BC. Within the body, different signaling pathways have been identified that contribute to cancer progression, or conversely, cancer prevention. Phosphatase and tensin homolog (PTEN) is one of the proteins that prevent cancer by inhibiting the oncogenic PI3K/Akt/mTOR signaling pathway. MicroRNAs (miRNAs) are molecules with about 18 to 28 base pairs, which regulate about 30% of human genes after transcription. miRNAs play a key role in the progression or prevention of cancer through different signaling pathway and mechanisms, e.g., apoptosis, angiogenesis, and proliferation. miRNAs, which are upstream mediators of PTEN, can reinforce or suppress the effect of PTEN signaling on BC cells, and suppressing the PTEN signaling, linked to weakness of the cancer cells to chemotherapeutic drugs. However, the precise mechanism and function of miRNAs on PTEN in BC are not yet fully understood. Therefore, in the present study, has been focused on miRNAs regulating PTEN function in BC.
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Affiliation(s)
- Mahya Mohammadi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ahmad Fazilat
- Department of Genetics, Motamed Cancer Institute, ACECR, Tehran, Iran
| | | | - Masoud Ojarudi
- Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Mohsen Hemmati-Dinarvand
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | | | - Mohammad Valilo
- Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
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Nogueras Pérez R, Heredia-Nicolás N, de Lara-Peña L, López de Andrés J, Marchal JA, Jiménez G, Griñán-Lisón C. Unraveling the Potential of miRNAs from CSCs as an Emerging Clinical Tool for Breast Cancer Diagnosis and Prognosis. Int J Mol Sci 2023; 24:16010. [PMID: 37958993 PMCID: PMC10647353 DOI: 10.3390/ijms242116010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/02/2023] [Accepted: 11/03/2023] [Indexed: 11/15/2023] Open
Abstract
Breast cancer (BC) is the most diagnosed cancer in women and the second most common cancer globally. Significant advances in BC research have led to improved early detection and effective therapies. One of the key challenges in BC is the presence of BC stem cells (BCSCs). This small subpopulation within the tumor possesses unique characteristics, including tumor-initiating capabilities, contributes to treatment resistance, and plays a role in cancer recurrence and metastasis. In recent years, microRNAs (miRNAs) have emerged as potential regulators of BCSCs, which can modulate gene expression and influence cellular processes like BCSCs' self-renewal, differentiation, and tumor-promoting pathways. Understanding the miRNA signatures of BCSCs holds great promise for improving BC diagnosis and prognosis. By targeting BCSCs and their associated miRNAs, researchers aim to develop more effective and personalized treatment strategies that may offer better outcomes for BC patients, minimizing tumor recurrence and metastasis. In conclusion, the investigation of miRNAs as regulators of BCSCs opens new directions for advancing BC research through the use of bioinformatics and the development of innovative therapeutic approaches. This review summarizes the most recent and innovative studies and clinical trials on the role of BCSCs miRNAs as potential tools for early diagnosis, prognosis, and resistance.
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Affiliation(s)
- Raquel Nogueras Pérez
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, 18016 Granada, Spain; (R.N.P.); (N.H.-N.); (L.d.L.-P.); (J.L.d.A.); (J.A.M.)
| | - Noelia Heredia-Nicolás
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, 18016 Granada, Spain; (R.N.P.); (N.H.-N.); (L.d.L.-P.); (J.L.d.A.); (J.A.M.)
| | - Laura de Lara-Peña
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, 18016 Granada, Spain; (R.N.P.); (N.H.-N.); (L.d.L.-P.); (J.L.d.A.); (J.A.M.)
- Biosanitary Research Institute of Granada (ibs. GRANADA), University Hospitals of Granada, University of Granada, 18012 Granada, Spain
- Excellence Research Unit “Modeling Nature” (MNat), University of Granada, 18016 Granada, Spain
- Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, 18016 Granada, Spain
| | - Julia López de Andrés
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, 18016 Granada, Spain; (R.N.P.); (N.H.-N.); (L.d.L.-P.); (J.L.d.A.); (J.A.M.)
- Biosanitary Research Institute of Granada (ibs. GRANADA), University Hospitals of Granada, University of Granada, 18012 Granada, Spain
- Excellence Research Unit “Modeling Nature” (MNat), University of Granada, 18016 Granada, Spain
- Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, 18016 Granada, Spain
| | - Juan Antonio Marchal
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, 18016 Granada, Spain; (R.N.P.); (N.H.-N.); (L.d.L.-P.); (J.L.d.A.); (J.A.M.)
- Biosanitary Research Institute of Granada (ibs. GRANADA), University Hospitals of Granada, University of Granada, 18012 Granada, Spain
- Excellence Research Unit “Modeling Nature” (MNat), University of Granada, 18016 Granada, Spain
- Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, 18016 Granada, Spain
| | - Gema Jiménez
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, 18016 Granada, Spain; (R.N.P.); (N.H.-N.); (L.d.L.-P.); (J.L.d.A.); (J.A.M.)
- Biosanitary Research Institute of Granada (ibs. GRANADA), University Hospitals of Granada, University of Granada, 18012 Granada, Spain
- Excellence Research Unit “Modeling Nature” (MNat), University of Granada, 18016 Granada, Spain
- Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, 18016 Granada, Spain
| | - Carmen Griñán-Lisón
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, 18016 Granada, Spain; (R.N.P.); (N.H.-N.); (L.d.L.-P.); (J.L.d.A.); (J.A.M.)
- Biosanitary Research Institute of Granada (ibs. GRANADA), University Hospitals of Granada, University of Granada, 18012 Granada, Spain
- Excellence Research Unit “Modeling Nature” (MNat), University of Granada, 18016 Granada, Spain
- Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain
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Singla RK, Wang X, Gundamaraju R, Joon S, Tsagkaris C, Behzad S, Khan J, Gautam R, Goyal R, Rakmai J, Dubey AK, Simal-Gandara J, Shen B. Natural products derived from medicinal plants and microbes might act as a game-changer in breast cancer: a comprehensive review of preclinical and clinical studies. Crit Rev Food Sci Nutr 2023; 63:11880-11924. [PMID: 35838143 DOI: 10.1080/10408398.2022.2097196] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Breast cancer (BC) is the most prevalent neoplasm among women. Genetic and environmental factors lead to BC development and on this basis, several preventive - screening and therapeutic interventions have been developed. Hormones, both in the form of endogenous hormonal signaling or hormonal contraceptives, play an important role in BC pathogenesis and progression. On top of these, breast microbiota includes both species with an immunomodulatory activity enhancing the host's response against cancer cells and species producing proinflammatory cytokines associated with BC development. Identification of novel multitargeted therapeutic agents with poly-pharmacological potential is a dire need to combat advanced and metastatic BC. A growing body of research has emphasized the potential of natural compounds derived from medicinal plants and microbial species as complementary BC treatment regimens, including dietary supplements and probiotics. In particular, extracts from plants such as Artemisia monosperma Delile, Origanum dayi Post, Urtica membranacea Poir. ex Savigny, Krameria lappacea (Dombey) Burdet & B.B. Simpson and metabolites extracted from microbes such as Deinococcus radiodurans and Streptomycetes strains as well as probiotics like Bacillus coagulans and Lactobacillus brevis MK05 have exhibited antitumor effects in the form of antiproliferative and cytotoxic activity, increase in tumors' chemosensitivity, antioxidant activity and modulation of BC - associated molecular pathways. Further, bioactive compounds like 3,3'-diindolylmethane, epigallocatechin gallate, genistein, rutin, resveratrol, lycopene, sulforaphane, silibinin, rosmarinic acid, and shikonin are of special interest for the researchers and clinicians because these natural agents have multimodal action and act via multiple ways in managing the BC and most of these agents are regularly available in our food and fruit diets. Evidence from clinical trials suggests that such products had major potential in enhancing the effectiveness of conventional antitumor agents and decreasing their side effects. We here provide a comprehensive review of the therapeutic effects and mechanistic underpinnings of medicinal plants and microbial metabolites in BC management. The future perspectives on the translation of these findings to the personalized treatment of BC are provided and discussed.
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Affiliation(s)
- Rajeev K Singla
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- iGlobal Research and Publishing Foundation, New Delhi, India
| | - Xiaoyan Wang
- Department of Pathology, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
| | - Rohit Gundamaraju
- ER Stress and Mucosal Immunology Lab, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania, Australia
| | - Shikha Joon
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- iGlobal Research and Publishing Foundation, New Delhi, India
| | | | - Sahar Behzad
- Evidence-based Phytotherapy and Complementary Medicine Research Center, Alborz University of Medical Sciences, Karaj, Iran
- Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Johra Khan
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah, Saudi Arabia
- Health and Basic Sciences Research Center, Majmaah University, Majmaah, Saudi Arabia
| | - Rupesh Gautam
- Department of Pharmacology, MM School of Pharmacy, MM University, Sadopur, Haryana, India
| | - Rajat Goyal
- Department of Pharmacology, MM School of Pharmacy, MM University, Sadopur, Haryana, India
| | - Jaruporn Rakmai
- Kasetsart Agricultural and Agro-Industrial Product Improvement Institute (KAPI), Kasetsart University, Bangkok, Thailand
| | | | - Jesus Simal-Gandara
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Science, Universidade de Vigo, Ourense, Spain
| | - Bairong Shen
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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12
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Wandrey M, Jablonska J, Stauber RH, Gül D. Exosomes in Cancer Progression and Therapy Resistance: Molecular Insights and Therapeutic Opportunities. Life (Basel) 2023; 13:2033. [PMID: 37895415 PMCID: PMC10608050 DOI: 10.3390/life13102033] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 10/04/2023] [Accepted: 10/05/2023] [Indexed: 10/29/2023] Open
Abstract
The development of therapy resistance still represents a major hurdle in treating cancers, leading to impaired treatment success and increased patient morbidity. The establishment of minimally invasive liquid biopsies is a promising approach to improving the early diagnosis, as well as therapy monitoring, of solid tumors. Because of their manifold functions in the tumor microenvironment, tumor-associated small extracellular vesicles, referred to as exosomes, have become a subject of intense research. Besides their important roles in cancer progression, metastasis, and the immune response, it has been proposed that exosomes also contribute to the acquisition and transfer of therapy resistance, mainly by delivering functional proteins and RNAs, as well as facilitating the export of active drugs or functioning as extracellular decoys. Extensive research has focused on understanding the molecular mechanisms underlying the occurrence of resistance and translating these into strategies for early detection. With this review, we want to provide an overview of the current knowledge about the (patho-)biology of exosomes, as well as state-of-the-art methods of isolation and analysis. Furthermore, we highlight the role of exosomes in tumorigenesis and cancer treatment, where they can function as therapeutic agents, biomarkers, and/or targets. By focusing on their roles in therapy resistance, we will reveal new paths of exploiting exosomes for cancer diagnosis and treatment.
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Affiliation(s)
- Madita Wandrey
- Nanobiomedicine/ENT Department, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany; (M.W.); (R.H.S.)
| | - Jadwiga Jablonska
- Translational Oncology/ENT Department, University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany;
- German Cancer Consortium (DKTK) Partner Site Düsseldorf/Essen, 45147 Essen, Germany
| | - Roland H. Stauber
- Nanobiomedicine/ENT Department, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany; (M.W.); (R.H.S.)
| | - Désirée Gül
- Nanobiomedicine/ENT Department, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany; (M.W.); (R.H.S.)
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13
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El-Ganainy SO, Shehata AM, El-Mallah A, Abdallah D, Mohy El-Din MM. Geraniol suppresses tumour growth and enhances chemosensitivity of 5-fluorouracil on breast carcinoma in mice: involvement of miR-21/PTEN signalling. J Pharm Pharmacol 2023:rgad060. [PMID: 37379815 DOI: 10.1093/jpp/rgad060] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 06/14/2023] [Indexed: 06/30/2023]
Abstract
OBJECTIVES Breast cancer is the most diagnosed cancer in females worldwide. Phytochemicals are among the recent compelling approaches showing anticancer activity. Geraniol is a monoterpenoid showing anti-tumoral potential in cell lines. However, its exact mechanism in breast cancer has not been elucidated. In addition, the possible chemosenstizing effect of geraniol when combined with chemotherapeutic drugs in breast carcinoma has not been previously addressed. METHODS Therefore, the aim of the current work is to investigate the potential therapeutic as well as chemosensitizing effects of geraniol on breast carcinoma induced in mice through examination of tumour biomarkers and histopathology profile. KEY FINDINGS Results showed a prominent suppression of tumour growth following geraniol treatment. This was accompanied with miR-21 downregulation that subsequently upregulated PTEN and suppressed mTOR levels. Geraniol was also able to activate apoptosis and inhibit autophagy. Histopathological examination revealed high necrosis areas separating malignant cells in the geraniol-treated group. Combined geraniol and 5-fluorouracil treatment induced more than 82% inhibition of tumour rate, surpassing the effect of each drug alone. CONCLUSIONS It can be concluded that geraniol could represent a promising avenue for breast cancer treatment as well as a potential sensitizing agent when combined with chemotherapeutic drugs.
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Affiliation(s)
- Samar O El-Ganainy
- Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt
| | - Asmaa M Shehata
- Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt
| | - Ahmed El-Mallah
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Dina Abdallah
- Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Mahmoud M Mohy El-Din
- Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt
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14
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Dwivedi M, Ghosh D, Saha A, Hasan S, Jindal D, Yadav H, Yadava A, Dwivedi M. Biochemistry of exosomes and their theranostic potential in human diseases. Life Sci 2023; 315:121369. [PMID: 36639052 DOI: 10.1016/j.lfs.2023.121369] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 12/22/2022] [Accepted: 01/01/2023] [Indexed: 01/11/2023]
Abstract
Exosomes are classified as special extracellular vesicles in the eukaryotic system having diameters ranging from 30 to 120 nm. These vesicles carry various endogenous molecules including DNA, mRNA, microRNA, circular RNA, and proteins, crucial for numerous metabolic reactions and can be proposed as therapeutic or diagnostic targets for several disorders. The donor exosomes release their content to recipient cells and further establish the significant intercellular communication showing biological effects by triggering environmental alterations. Exosomes derived from mesenchymal and dendritic cells have demonstrated their therapeutic potential against organ injury. Yet, various intricacies are involved in exosomal transport and its inclusion in cancer and other disease pathogenesis needs to be explored. The exosomes represent profound potential as diagnostic biomarkers and therapeutic carriers in various pathophysiological conditions such as neurodegenerative diseases, chronic cancers, infectious diseases, female reproductive diseases and cardiovascular diseases. In the current study, we demonstrate the advancements in the implication of exosomes as one of the irrefutable prognostic biological targets in human health and diseases.
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Affiliation(s)
- Manish Dwivedi
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow 226028, India.
| | - Diya Ghosh
- Department of Biotechnology, Heritage Institute of Technology, Kolkata, West Bengal, India
| | - Anwesha Saha
- Department of Biotechnology, Heritage Institute of Technology, Kolkata, West Bengal, India
| | - Saba Hasan
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow 226028, India
| | - Divya Jindal
- Center for Emerging Diseases, Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
| | - Hitendra Yadav
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow 226028, India
| | - Anuradha Yadava
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow 226028, India
| | - Medha Dwivedi
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow 226028, India
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15
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Hashemi M, Mirdamadi MSA, Talebi Y, Khaniabad N, Banaei G, Daneii P, Gholami S, Ghorbani A, Tavakolpournegari A, Farsani ZM, Zarrabi A, Nabavi N, Zandieh MA, Rashidi M, Taheriazam A, Entezari M, Khan H. Pre-clinical and clinical importance of miR-21 in human cancers: Tumorigenesis, therapy response, delivery approaches and targeting agents. Pharmacol Res 2023; 187:106568. [PMID: 36423787 DOI: 10.1016/j.phrs.2022.106568] [Citation(s) in RCA: 52] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 11/18/2022] [Accepted: 11/19/2022] [Indexed: 11/23/2022]
Abstract
The field of non-coding RNA (ncRNA) has made significant progress in understanding the pathogenesis of diseases and has broadened our knowledge towards their targeting, especially in cancer therapy. ncRNAs are a large family of RNAs with microRNAs (miRNAs) being one kind of endogenous RNA which lack encoded proteins. By now, miRNAs have been well-coined in pathogenesis and development of cancer. The current review focuses on the role of miR-21 in cancers and its association with tumor progression. miR-21 has both oncogenic and onco-suppressor functions and most of the experiments are in agreement with the tumor-promoting function of this miRNA. miR-21 primarily decreases PTEN expression to induce PI3K/Akt signaling in cancer progression. Overexpression of miR-21 inhibits apoptosis and is vital for inducing pro-survival autophagy. miR-21 is vital for metabolic reprogramming and can induce glycolysis to enhance tumor progression. miR-21 stimulates EMT mechanisms and increases expression of MMP-2 and MMP-9 thereby elevating tumor metastasis. miR-21 is a target of anti-cancer agents such as curcumin and curcumol and its down-regulation impairs tumor progression. Upregulation of miR-21 results in cancer resistance to chemotherapy and radiotherapy. Increasing evidence has revealed the role of miR-21 as a biomarker as it is present in both the serum and exosomes making them beneficial biomarkers for non-invasive diagnosis of cancer.
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Affiliation(s)
- Mehrdad Hashemi
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran
| | - Motahare Sadat Ayat Mirdamadi
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran; Department of Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Yasmin Talebi
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran; Department of Biology, Islamic Azad University Central Tehran Branch, Tehran, Iran
| | - Nasrin Khaniabad
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran
| | - Gooya Banaei
- Group of Mutagenesis, Department of Genetics and Microbiology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain
| | - Pouria Daneii
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran
| | - Sadaf Gholami
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran
| | - Amin Ghorbani
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran; Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Alireza Tavakolpournegari
- Group of Mutagenesis, Department of Genetics and Microbiology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain
| | - Zoheir Mohammadian Farsani
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran; Department of Industrial and Environmental Biotechnology, National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
| | - Ali Zarrabi
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul 34396, Turkey
| | - Noushin Nabavi
- Department of Urological Sciences and Vancouver Prostate Centre, University of British Columbia, Vancouver, BC V6H3Z6, Canada
| | - Mohammad Arad Zandieh
- Department of Food Hygiene and Quality Control, Division of epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Mohsen Rashidi
- Department Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Afshin Taheriazam
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Maliheh Entezari
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran.
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University Mardan, 23200, Pakistan.
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16
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Brain AVMs-Related microRNAs: Machine Learning Algorithm for Expression Profiles of Target Genes. Brain Sci 2022; 12:brainsci12121628. [PMID: 36552089 PMCID: PMC9775264 DOI: 10.3390/brainsci12121628] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 11/20/2022] [Accepted: 11/25/2022] [Indexed: 11/29/2022] Open
Abstract
INTRODUCTION microRNAs (miRNAs) are a class of non-coding RNAs playing a myriad of important roles in regulating gene expression. Of note, recent work demonstrated a critical role of miRNAs in the genesis and progression of brain arteriovenous malformations (bAVMs). Accordingly, here we examine miRNA signatures related to bAVMs and associated gene expression. In so doing we expound on the potential prognostic, diagnostic, and therapeutic significance of miRNAs in the clinical management of bAVMs. METHODS A PRISMA-based literature review was performed using PubMed/Medline database with the following search terms: "brain arteriovenous malformations", "cerebral arteriovenous malformations", "microRNA", and "miRNA". All preclinical and clinical studies written in English, regardless of date, were selected. For our bioinformatic analyses, miRWalk and miRTarBase machine learning algorithms were employed; the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was quired for associated pathways/functions. RESULTS four studies were ultimately included in the final analyses. Sequencing data consistently revealed the decreased expression of miR-18a in bAVM-endothelial cells, resulting in increased levels of vascular endodermal growth factor (VEGF), Id-1, matrix metalloproteinase, and growth signals. Our analyses also suggest that the downregulation of miR-137 and miR-195* within vascular smooth muscle cells (VSMCs) may foster the activation of inflammation, aberrant angiogenesis, and phenotypic switching. In the peripheral blood, the overexpression of miR-7-5p, miR-629-5p, miR-199a-5p, miR-200b-3p, and let-7b-5p may contribute to endothelial proliferation and nidus development. The machine learning algorithms employed confirmed associations between miRNA-related target networks, vascular rearrangement, and bAVM progression. CONCLUSION miRNAs expression appears to be critical in managing bAVMs' post-transcriptional signals. Targets of microRNAs regulate canonical vascular proliferation and reshaping. Although additional scientific evidence is needed, the identification of bAVM miRNA signatures may facilitate the development of novel prognostic/diagnostic tools and molecular therapies for bAVMs.
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Gulati R, Nandi D, Sarkar K, Venkataraman P, Ramkumar KM, Ranjan P, Janardhanan R. Exosomes as Theranostic Targets: Implications for the Clinical Prognosis of Aggressive Cancers. Front Mol Biosci 2022; 9:890768. [PMID: 35813829 PMCID: PMC9260243 DOI: 10.3389/fmolb.2022.890768] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 05/20/2022] [Indexed: 12/12/2022] Open
Abstract
Exosomes are extracellular vesicles produced by various cell types and extensively distributed in physiological fluids. Because of their significant role in cancer progression, they have been a focal point for the novel cancer therapy approach. Exosomes are highly efficient at transporting proteins, RNAs, and small drugs into cancer cells for therapeutic purposes. In addition to their prominent role as potential biomarkers for transporting targeted information from their progenitor cells, exosomes have also emerged as a new avenue for developing more effective clinical diagnostics and therapeutic techniques, also known as exosome theranostics. Lipids, proteins, and nucleic acids transported by exosomes were investigated as potential biomarkers for cancer diagnosis, prognosis, and future cancer treatment targets. The unique mechanism of exosomes and their therapeutic as well as diagnostic uses, also known as theranostic applications of exosomes in malignancies, are discussed in this review.
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Affiliation(s)
- Richa Gulati
- Department of Medical Research, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, Kattankulathur, India
| | - Dhruva Nandi
- Department of Medical Research, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, Kattankulathur, India
| | - Koustav Sarkar
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, India
| | - P. Venkataraman
- Department of Medical Research, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, Kattankulathur, India
| | - K. M. Ramkumar
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, India
| | - Priya Ranjan
- Bhubaneswar Institute of Technology, Rourkela, India
| | - Rajiv Janardhanan
- Department of Medical Research, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, Kattankulathur, India
- *Correspondence: Rajiv Janardhanan,
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18
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Saha T, Lukong KE. Breast Cancer Stem-Like Cells in Drug Resistance: A Review of Mechanisms and Novel Therapeutic Strategies to Overcome Drug Resistance. Front Oncol 2022; 12:856974. [PMID: 35392236 PMCID: PMC8979779 DOI: 10.3389/fonc.2022.856974] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 02/21/2022] [Indexed: 12/12/2022] Open
Abstract
Breast cancer is the most frequent type of malignancy in women worldwide, and drug resistance to the available systemic therapies remains a major challenge. At the molecular level, breast cancer is heterogeneous, where the cancer-initiating stem-like cells (bCSCs) comprise a small yet distinct population of cells within the tumor microenvironment (TME) that can differentiate into cells of multiple lineages, displaying varying degrees of cellular differentiation, enhanced metastatic potential, invasiveness, and resistance to radio- and chemotherapy. Based on the expression of estrogen and progesterone hormone receptors, expression of human epidermal growth factor receptor 2 (HER2), and/or BRCA mutations, the breast cancer molecular subtypes are identified as TNBC, HER2 enriched, luminal A, and luminal B. Management of breast cancer primarily involves resection of the tumor, followed by radiotherapy, and systemic therapies including endocrine therapies for hormone-responsive breast cancers; HER2-targeted therapy for HER2-enriched breast cancers; chemotherapy and poly (ADP-ribose) polymerase inhibitors for TNBC, and the recent development of immunotherapy. However, the complex crosstalk between the malignant cells and stromal cells in the breast TME, rewiring of the many different signaling networks, and bCSC-mediated processes, all contribute to overall drug resistance in breast cancer. However, strategically targeting bCSCs to reverse chemoresistance and increase drug sensitivity is an underexplored stream in breast cancer research. The recent identification of dysregulated miRNAs/ncRNAs/mRNAs signatures in bCSCs and their crosstalk with many cellular signaling pathways has uncovered promising molecular leads to be used as potential therapeutic targets in drug-resistant situations. Moreover, therapies that can induce alternate forms of regulated cell death including ferroptosis, pyroptosis, and immunotherapy; drugs targeting bCSC metabolism; and nanoparticle therapy are the upcoming approaches to target the bCSCs overcome drug resistance. Thus, individualizing treatment strategies will eliminate the minimal residual disease, resulting in better pathological and complete response in drug-resistant scenarios. This review summarizes basic understanding of breast cancer subtypes, concept of bCSCs, molecular basis of drug resistance, dysregulated miRNAs/ncRNAs patterns in bCSCs, and future perspective of developing anticancer therapeutics to address breast cancer drug resistance.
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Affiliation(s)
- Taniya Saha
- Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada
| | - Kiven Erique Lukong
- Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada
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19
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Wu R, Zhou S, Liu M, An H, Wang Z, Liu T. Clinical Significance of miR-21-5p in Predicting Occurrence and Progression of Uremic Vascular Calcification in Patients with End-Stage Renal Disease. Yonsei Med J 2022; 63:252-258. [PMID: 35184427 PMCID: PMC8860934 DOI: 10.3349/ymj.2022.63.3.252] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 10/29/2021] [Accepted: 11/12/2021] [Indexed: 11/27/2022] Open
Abstract
PURPOSE Vascular calcification (VC) is a common complication of end-stage renal disease (ESRD). This study aimed to examine changes in the expression of miR-21-5p in ESRD patients with VC and to explore its clinical value in predicting the occurrence and progression of uremic VC. MATERIALS AND METHODS 120 ESRD patients were divided into patients without VC group (n=38) and patients with VC group (n=82). All patients were followed up for 2 years to evaluate VC progression. qRT-PCR was used to detect serum miR-21-5p levels. Receiver operating characteristic curves were constructed to assess diagnostic value. Kaplan-Meier and log-rank methods were utilized to calculate associations between VC progression and risk factors. RESULTS Serum miR-21-5p levels were significantly higher in ESRD patients with VC than in those without VC and increased progressively with increasing disease severity. Serum miR-21-5p levels were able to distinguish patients with VC from those without VC, with an area under the curve value of 0.883, a sensitivity of 81.7%, and a specificity of 84.2%. After 2 years of follow-up, miR-21-5p expression had increased in patients with worse VC severity, compared with those with stable VC severity. Patients with high miR-21-5p levels were more likely to develop more severe VC, indicating an association between miR-21-5p and VC progression (log-rank p=0.002). Multivariable Cox regression analysis suggested that serum miR-21-5p is an independent predictive factor of VC progression in ESRD patients (hazard ratio=2.064, 95% confidence interval=1.225-3.478, p=0.006). CONCLUSION miR-21-5p is overexpressed in the serum of ESRD patients with VC. Our results suggest that overexpression of miR-21-5p is closely associated with VC progression.
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Affiliation(s)
- Rong Wu
- Department of Nephropathy, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Sen Zhou
- Department of Nephropathy, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Minglong Liu
- Department of Nephropathy, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Haiqian An
- Department of Nephropathy, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Zhe Wang
- Department of Nephropathy, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Tianxi Liu
- Department of Nephropathy, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.
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20
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Role of tumour-derived exosomes in metastasis. Biomed Pharmacother 2022; 147:112657. [DOI: 10.1016/j.biopha.2022.112657] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 01/15/2022] [Accepted: 01/18/2022] [Indexed: 12/15/2022] Open
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21
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Tissue miR-200c-3p and circulating miR-1290 as potential prognostic biomarkers for colorectal cancer. Sci Rep 2022; 12:2295. [PMID: 35145164 PMCID: PMC8831555 DOI: 10.1038/s41598-022-06192-w] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 01/25/2022] [Indexed: 01/09/2023] Open
Abstract
Epithelial–mesenchymal transition (EMT)-related cancers generally elicit low immune responses. EMT is regulated by several microRNAs (miRNAs) in cancers. Thus, this study aimed to evaluate the prognostic potential of EMT-related miRNAs as biomarkers in colorectal cancer (CRC). Formalin-fixed paraffin-embedded tumor and normal tissue and plasma samples were obtained from 65 patients with pathologically confirmed CRC. In addition, plasma samples were obtained from 30 healthy volunteers. Immunohistochemical staining for E-cadherin, ZEB1, PD-1, PD-L1, CD3, CD4, CD8, Foxp3, and CD68 was conducted on tissue samples. Droplet digital polymerase chain reaction (ddPCR) analysis was performed to evaluate miR-21-5p, 34a-5p, 138-5p, 200a-3p, 200b-5p, 200c-3p, 630, 1246, and 1290 expression in tissue samples and miR-630, 1246, and 1290 expression in plasma samples. miR-21-5p, 34a-5p, 630, 1246, and 1290 expression was higher in tumor tissues than in normal tissues (P < 0.05). EMT was significantly associated with reduced tumor-infiltrating T cells. Moreover, miR-21-5p, miR-34a-5p, miR-200a-3p, and miR-200c-3p expression was negatively correlated with T cell density (P < 0.05). High tissue levels of miR-200c-3p were associated with poor overall survival (OS) (P < 0.001). CRC patients with the EMT phenotype had poor OS; however, PD-L1 positivity and abundant PD-1 positive immune cells were correlated with better OS (P < 0.05). miR-1246 and miR-1290 levels were significantly higher in the plasma of patients with CRC than in the plasma of healthy controls (P < 0.05). High plasma levels of miR-1290 were correlated with advanced stage and poor OS (P < 0.05). The tissue expression of miR-200c-3p and plasma levels of miR-1290 measured by ddPCR indicate their potential as prognostic biomarkers for CRC.
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Onco-miR-21 Promotes Stat3-Dependent Gastric Cancer Progression. Cancers (Basel) 2022; 14:cancers14020264. [PMID: 35053428 PMCID: PMC8773769 DOI: 10.3390/cancers14020264] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 12/24/2021] [Accepted: 12/29/2021] [Indexed: 12/22/2022] Open
Abstract
MicroRNA-21 (miR-21) is a small, non-coding RNA overexpressed in gastric cancer and many other solid malignancies, where it exhibits both pro-and anti-tumourigenic properties. However, the pathways regulating miR-21 and the consequences of its inhibition in gastric cancer remain incompletely understood. By exploiting the spontaneous Stat3-dependent formation of inflammation-associated gastric tumors in Gp130F/F mice, we functionally established miR-21 as a Stat3-controlled driver of tumor growth and progression. We reconciled our discoveries by identifying several conserved Stat3 binding motifs upstream of the miR-21 gene promoter, and showed that the systemic administration of a miR-21-specific antisense oligonucleotide antagomir reduced the established gastric tumor burden in Gp130F/F mice. We molecularly delineated the therapeutic benefits of miR-21 inhibition with the functional restoration of PTEN in vitro and in vivo, alongside an attenuated epithelial-to-mesenchymal transition and the extracellular matrix remodeling phenotype of tumors. We corroborated our preclinical findings by correlating high STAT3 and miR-21 expression with the reduced survival probability of gastric cancer patients. Collectively, our results provide a molecular framework by which miR-21 mediates inflammation-associated gastric cancer progression, and establish miR-21 as a robust therapeutic target for solid malignancies characterized by excessive Stat3 activity.
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Amirfallah A, Knutsdottir H, Arason A, Hilmarsdottir B, Johannsson OT, Agnarsson BA, Barkardottir RB, Reynisdottir I. Hsa-miR-21-3p associates with breast cancer patient survival and targets genes in tumor suppressive pathways. PLoS One 2021; 16:e0260327. [PMID: 34797887 PMCID: PMC8604322 DOI: 10.1371/journal.pone.0260327] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 11/06/2021] [Indexed: 12/22/2022] Open
Abstract
Breast cancer is the cancer most often diagnosed in women. MicroRNAs (MIRs) are short RNA molecules that bind mRNA resulting in their downregulation. MIR21 has been shown to be an oncomiR in most cancer types, including breast cancer. Most of the effects of miR-21 have been attributed to hsa-miR-21-5p that is transcribed from the leading strand of MIR21, but hsa-miR-21-3p (miR-21-3p), transcribed from the lagging strand, is much less studied. The aim of the study is to analyze whether expression of miR-21-3p is prognostic for breast cancer. MiR-21-3p association with survival, clinical and pathological characteristics was analyzed in a large breast cancer cohort and validated in three separate cohorts, including TCGA and METABRIC. Analytical tools were also used to infer miR-21-3p function and to identify potential target genes and functional pathways. The results showed that in the exploration cohort, high miR-21-3p levels associated with shorter survival and lymph node positivity. In the three validation cohorts, high miR-21-3p levels associated with pathological characteristics that predict worse prognosis. Specifically, in the largest validation cohort, METABRIC (n = 1174), high miR-21-3p levels associated with large tumors, a high grade, lymph node and HER2 positivity, and shorter breast-cancer-specific survival (HR = 1.38, CI 1.13–1.68). This association remained significant after adjusting for confounding factors. The genes with expression levels that correlated with miR-21-3p were enriched in particular pathways, including the epithelial-to-mesenchymal transition and proliferation. Among the most significantly downregulated targets were MAT2A and the tumor suppressive genes STARD13 and ZNF132. The results from this study emphasize that both 3p- and 5p-arms from a MIR warrant independent study. The data show that miR-21-3p overexpression in breast tumors is a marker of worse breast cancer progression and it affects genes in pathways that drive breast cancer by down-regulating tumor suppressor genes. The results suggest miR-21-3p as a potential biomarker.
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Affiliation(s)
- Arsalan Amirfallah
- Cell Biology Unit, Department of Pathology, Landspitali–The National University Hospital of Iceland, Reykjavik, Iceland
- Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | - Hildur Knutsdottir
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America
| | - Adalgeir Arason
- Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- Molecular Pathology Unit, Department of Pathology, Landspitali–The National University Hospital of Iceland, Reykjavik, Iceland
| | - Bylgja Hilmarsdottir
- Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- Molecular Pathology Unit, Department of Pathology, Landspitali–The National University Hospital of Iceland, Reykjavik, Iceland
| | - Oskar T. Johannsson
- Department of Pathology, Landspitali–The National University Hospital of Iceland, Reykjavik, Iceland
| | - Bjarni A. Agnarsson
- Department of Oncology, Landspitali–The National University Hospital of Iceland, Reykjavik, Iceland
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | - Rosa B. Barkardottir
- Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- Molecular Pathology Unit, Department of Pathology, Landspitali–The National University Hospital of Iceland, Reykjavik, Iceland
| | - Inga Reynisdottir
- Cell Biology Unit, Department of Pathology, Landspitali–The National University Hospital of Iceland, Reykjavik, Iceland
- Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- * E-mail:
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Akbarzadeh M, Mihanfar A, Akbarzadeh S, Yousefi B, Majidinia M. Crosstalk between miRNA and PI3K/AKT/mTOR signaling pathway in cancer. Life Sci 2021; 285:119984. [PMID: 34592229 DOI: 10.1016/j.lfs.2021.119984] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 09/09/2021] [Accepted: 09/19/2021] [Indexed: 01/07/2023]
Abstract
Phosphoinositide-3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway is one of the most important proliferative signaling pathways with critical undeniable function in various aspects of cancer initiation/progression, including proliferation, apoptosis, metastasis, angiogenesis, and drug resistance. On the other hand, numerous genetic alterations in the key genes involved in the PI3K/AKT/mTOR signaling pathway have been identified in multiple solid and hematological tumors. In addition, accumulating recent evidences have demonstrated a reciprocal interaction between this signaling pathway and microRNAs, a large group of small non-coding RNAs. Therefore, in this review, it was attempted to discuss about the interaction between key components of PI3K/AKT/mTOR signaling pathway with various miRNAs and their importance in cancer biology.
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Affiliation(s)
- Maryam Akbarzadeh
- Department of biochemistry, Urmia University of Medical Sciences, Urmia, Iran
| | - Ainaz Mihanfar
- Department of biochemistry, Urmia University of Medical Sciences, Urmia, Iran
| | - Shabnam Akbarzadeh
- Department of Physical Education and Sport Medicine, University of Tabriz, Tabriz, Iran
| | - Bahman Yousefi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Majidinia
- Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, Iran.
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25
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Liu M, Deng H, Zhao Y, Li C, Liu H. Impact of microRNA -21 -5p on the growth of thyroid cancer cells via targeting the recombinant sclerostin domain containing protein 1. ZHONG NAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF CENTRAL SOUTH UNIVERSITY. MEDICAL SCIENCES 2021; 46:1054-1062. [PMID: 34911834 PMCID: PMC10930239 DOI: 10.11817/j.issn.1672-7347.2021.200764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Indexed: 11/03/2022]
Abstract
OBJECTIVES To explore the molecular mechanism for thyroid cancer metastasis via analyzing the role of microRNA (miR)-21-5p and its target gene recombinant sclerostin domain containing protein 1 (SOSTDC1) in thyroid cancer. METHODS The target miR-21-5p was screened through bioinformatics analysis and cell verification, and the thyroid cancer cell lines was transfected with miR-21-5p inhibitor. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, flow cytometry, and cell scratch test were used to detect the proliferation, apoptosis and migration of thyroid cancer cells in the miR-21-5p inhibitor group and the inhibitor control group, respectively. The luciferase report experiment was used to verify the relationship between miR-21-5p and SOSTDC1, Western blotting was used to detect the expression levels and phosphorylation levels of SOSTDC1,phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt) and mitogen-activated protein kinases (MAPK), extracellular regulated protein kinases (ERK) in thyroid cancer cells. RESULTS MiR-21-5p was significantly increased in thyroid cancer cells,which was negatively correlated with SOSTDC1 (r=-0.24, P<0.01). The proliferation and migration of thyroid cancer cells in the miR-21-5p inhibitor group was significantly lower than that in the inhibitor control group (both P<0.01), and the apoptosis rate in the miR-21-5p inhibitor group was significantly higher than that in the inhibitor control group (P<0.01).The luciferase report experiment showed that miR-21-5p could target and regulate the expression level of SOSTDC1, and the expression of PI3K in the miR-21-5p inhibitor group was significantly lower than that in the inhibitor control group (P<0.01). There were no significant changes in Akt and ERK1/2 levels, but the phosphorylation levels of Akt and ERK1/2 in the miR-21-5p inhibitor group were significantly lower than those in the inhibitor control group (both P<0.01). CONCLUSIONS MiR-21-5p in thyroid cancer cells can target the expression of SOSTDC1 and affect the activities of PI3K/Akt and MAPK/ERK, thereby inhibiting the apoptosis of thyroid cancer cells and promoting cell proliferation and migration.
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Affiliation(s)
- Miaomiao Liu
- Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
| | - Haoyu Deng
- Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Yajie Zhao
- Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Can Li
- Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Hua Liu
- Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
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Abstract
MicroRNAs (miRNAs), a class of small noncoding RNA, posttranscriptionally regulate the expression of genes. Aberrant expression of miRNA is reported in various types of cancer. Since the first report of oncomiR-21 involvement in the glioma, its upregulation was reported in multiple cancers and was allied with high oncogenic property. In addition to the downregulation of tumor suppressor genes, the miR-21 is also associated with cancer resistance to various chemotherapy. The recent research is appraising miR-21 as a promising cancer target and biomarker for early cancer detection. In this review, we briefly explain the biogenesis and regulation of miR-21 in cancer cells. Additionally, the review features the assorted genes/pathways regulated by the miR-21 in various cancer and cancer stem cells.
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Prajapati KS, Shuaib M, Kushwaha PP, Singh AK, Kumar S. Identification of cancer stemness related miRNA(s) using integrated bioinformatics analysis and in vitro validation. 3 Biotech 2021; 11:446. [PMID: 34631347 PMCID: PMC8460704 DOI: 10.1007/s13205-021-02994-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 09/10/2021] [Indexed: 02/05/2023] Open
Abstract
The stemness property of cells allows them to sustain their lineage, differentiation, proliferation, and regeneration. MicroRNAs are small non-coding RNAs known to regulate the stemness property of cells by regulating the expression of stem cell signaling pathway proteins at mRNA level. Dysregulated miRNA expression and associated stem cell signaling pathways in normal stem cells give rise to cancer stem cells. Thus, the present study was aimed to identify the miRNAs involved in the regulation of major stem cell signaling pathways. The proteins (n = 36) involved in the signaling pathways viz., Notch, Wnt, JAK-STAT, and Hedgehog which is associated with the stemness property was taken into the consideration. The miRNAs, having binding sites for the targeted protein-encoding gene were predicted using an online tool (TargetScan) and the common miRNA among the test pathways were identified using Venn diagram analysis. A total of 22 common miRNAs (including 8 non-studied miRNAs) were identified which were subjected to target predictions, KEGG pathway, and gene ontology (GO) analysis to study their potential involvement in the stemness process. Further, we studied the clinical relevance of the non-studied miRNAs by performing the survival analysis and their expression levels in clinical breast cancer patients using the TCGA database. The identified miRNAs showed overall poor survival in breast cancer patients. The miR-6844 showed significantly high expression in various clinical subgroups of invasive breast cancer patients compared with the normal samples. The expression levels of identified miRNA(s) were validated in breast normal, luminal A, triple-negative, and stem cells in vitro models using qRT-PCR analysis. Further treatment with the phytochemical showed excellent down regulation of the lead miRNA. Overall the study first time reports the association of four miRNAs (miR-6791, miR-4419a, miR-4251 and miR-6844) with breast cancer stemness. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s13205-021-02994-3.
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Affiliation(s)
- Kumari Sunita Prajapati
- Molecular Signaling & Drug Development Laboratory, Department of Biochemistry, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151401 India
| | - Mohd Shuaib
- Molecular Signaling & Drug Development Laboratory, Department of Biochemistry, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151401 India
| | - Prem Prakash Kushwaha
- Molecular Signaling & Drug Development Laboratory, Department of Biochemistry, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151401 India
| | - Atul Kumar Singh
- Molecular Signaling & Drug Development Laboratory, Department of Biochemistry, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151401 India
| | - Shsahank Kumar
- Molecular Signaling & Drug Development Laboratory, Department of Biochemistry, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151401 India
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Otero-Albiol D, Carnero A. Cellular senescence or stemness: hypoxia flips the coin. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2021; 40:243. [PMID: 34325734 PMCID: PMC8323321 DOI: 10.1186/s13046-021-02035-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 07/05/2021] [Indexed: 01/10/2023]
Abstract
Cellular senescence is a complex physiological state whose main feature is proliferative arrest. Cellular senescence can be considered the reverse of cell immortalization and continuous tumor growth. However, cellular senescence has many physiological functions beyond being a putative tumor suppressive trait. It remains unknown whether low levels of oxygen or hypoxia, which is a feature of every tissue in the organism, modulate cellular senescence, altering its capacity to suppress the limitation of proliferation. It has been observed that the lifespan of mammalian primary cells is increased under low oxygen conditions. Additionally, hypoxia promotes self-renewal and pluripotency maintenance in adult and embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and cancer stem cells (CSCs). In this study, we discuss the role of hypoxia facilitating senescence bypass during malignant transformation and acquisition of stemness properties, which all contribute to tumor development and cancer disease aggressiveness.
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Affiliation(s)
- Daniel Otero-Albiol
- Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Consejo Superior de Investigaciones Científicas, Avda. Manuel Siurot s/n, 41013, Seville, Spain.,CIBER de CANCER, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Amancio Carnero
- Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Consejo Superior de Investigaciones Científicas, Avda. Manuel Siurot s/n, 41013, Seville, Spain. .,CIBER de CANCER, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
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Jadhav KB, Shah V, Chauhan N, Shah N, Parmar G. Expression of microRNA-21 in saliva and tumor tissue of patients with oral squamous cell carcinoma: a predictor of cervical lymph node metastasis. Oral Surg Oral Med Oral Pathol Oral Radiol 2021; 133:60-69. [PMID: 34518132 DOI: 10.1016/j.oooo.2021.07.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 07/06/2021] [Accepted: 07/13/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Evaluation of diagnostic accuracy of microRNA-21 (miR-21) in saliva and tumor tissue for presurgical assessment of lymph node metastasis in patients with oral squamous cell carcinoma (OSCC). STUDY DESIGN Unstimulated whole saliva and tumor tissue was obtained from clinically suspected patients with OSCC. A total of 130 patients diagnosed with OSCC were included as study participants. The assessment of cervical lymph node metastasis was done before surgery using imaging scans and post surgically confirmed by histopathologic examination of excised lymph nodes. miR-21 expression was evaluated using real-time polymerase chain reaction. The data was statistically analyzed for correlation analysis, cutoff values, sensitivity, and specificity. The κ statistic was applied to assess the degree of agreement between the lymph node metastasis and miR-21 expression. RESULTS miR-21 expression showed a statistically significant correlation with cervical lymph node metastasis with a diagnostic accuracy of 65% to 71.54% in saliva and 69% to 81.54% in tumor tissue. Very good agreement was observed between tumor tissue miR-21-3p and cervical lymph node metastasis with a specificity of 80.60% and a sensitivity of 82.40%. CONCLUSIONS miR-21 expression in saliva and tumor tissue of patients with OSCC showed high diagnostic accuracy for assessment of cervical lymph node metastasis. It can be used as an alternative for assessment of cervical lymph node metastasis before surgery.
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Affiliation(s)
- Kiran B Jadhav
- PhD Scholar, Department of Oral Pathology and Microbiology, K M Shah Dental College and Hospital, Sumandeep Vidyapeeth, Piparia, Vadodara, Gujarat, India; Professor, Department of Oral Pathology and Microbiology, Vasant Dada Patil Dental College and Hospital, Maharashtra University of Health Sciences, Sangli, India.
| | - Vandana Shah
- Professor and Head, Department of Oral Pathology and Microbiology, K M Shah Dental College and Hospital, Sumandeep Vidyapeeth, Piparia, Vadodara, Gujarat, India
| | - Nirali Chauhan
- Professor, Department of ENT, Smt. B K Shah Medical College and Research Centre, Sumandeep Vidyapeeth, Piparia, Vadodara, Gujarat, India
| | - Naveen Shah
- Professor and Head, Department of Oral and Maxillofacial Surgery, K M Shah Dental College and Hospital, Sumandeep Vidyapeeth, Piparia, Vadodara. Gujarat, India
| | - Ghanshyam Parmar
- Associate Professor, Department of Pharmacy, Sumandeep Vidyapeeth, Piparia, Vadodara, Gujarat, India
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Taefehshokr S, Taefehshokr N, Derakhshani A, Baghbanzadeh A, Astamal RV, Safaei S, Abbasi S, Hajazimian S, Maroufi NF, Isazadeh A, Hajiasgharzadeh K, Baradaran B. The regulatory role of pivotal microRNAs in the AKT signaling pathway in breast cancer. Curr Mol Med 2021; 22:263-273. [PMID: 34238182 DOI: 10.2174/1566524021666210708095051] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 04/29/2021] [Accepted: 05/06/2021] [Indexed: 11/22/2022]
Abstract
Breast cancer is the most prevalent type of cancer among women, and it remains the main challenge despite improved treatments. MicroRNAs (miRNAs) are a small non-coding family of RNAs that play an indispensable role in regulating major physiological processes, including differentiation, proliferation, invasion, migration, cell cycle regulation, stem cell maintenance, apoptosis, and organ development. The dysregulation of these tiny molecules is associated with various human malignancies. More than 50% of these non-coding RNA sequences estimated have been placed on genomic regions or fragile sites linked to cancer. Following the discovery of the first signatures of specific miRNA in breast cancer, numerous researches focused on involving these tiny RNAs in breast cancer physiopathology as a new therapeutic approach or as reliable prognostic biomarkers. In the current review, we focus on recent findings related to the involvement of miRNAs in breast cancer via the AKT signaling pathway and the related clinical implications.
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Affiliation(s)
- Sina Taefehshokr
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nima Taefehshokr
- Division of Biosciences, Department of Life Sciences, Brunel University London, Kingston Lane, UB8 3PH, United Kingdom
| | - Afshin Derakhshani
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Baghbanzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Vaezi Astamal
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sahar Safaei
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Samane Abbasi
- Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran
| | - Saba Hajazimian
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nazila Fathi Maroufi
- Department of Clinical Biochemistry and Laboratory Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Isazadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Ghaderi F, Jokar N, Gholamrezanezhad A, Assadi M, Ahmadzadehfar H. Toward radiotheranostics in cancer stem cells: a promising initial step for tumour eradication. Clin Transl Imaging 2021. [DOI: 10.1007/s40336-021-00444-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Garcia E, Luna I, Persad KL, Agopsowicz K, Jay DA, West FG, Hitt MM, Persad S. Inhibition of triple negative breast cancer metastasis and invasiveness by novel drugs that target epithelial to mesenchymal transition. Sci Rep 2021; 11:11757. [PMID: 34083676 PMCID: PMC8175347 DOI: 10.1038/s41598-021-91344-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 05/24/2021] [Indexed: 12/26/2022] Open
Abstract
Invasive breast cancer (BrCa) is predicted to affect 1 in 9 women in a lifetime;1 in 32 will die from this disease. The most aggressive forms of BrCa, basal-like/triple-negative phenotype (TNBC), are challenging to treat and result in higher mortality due high number of metastatic cases. There is a paucity of options for TNBC treatment, which highlights the need for additional innovative treatment approaches. NIH-III mice were injected in the abdominal mammary fat pad with luciferase-expressing derivative of the human TNBC cell line, MDA-MB-231 cells. Animals were gavage-fed with nitrofen at the doses of 1, 3 or 6 mg/kg/alternate days. However, several structural properties/components of nitrofen raise concerns, including its high lipophilicity (cLogP of nearly 5) and a potential toxophore in the form of a nitroarene group. Therefore, we developed analogues of nitrofen which lack the nitro group and/or have replaced the diaryl ether linker with a diarylamine that could allow modulation of polarity. In vitro anti-invasiveness activity of nitrofen analogues were evaluated by quantitative determination of invasion of MDA-MB-231-Luciferase cells through Matrigel using a Boyden chamber. Our in vivo data show that nitrofen efficiently blocks TNBC tumor metastasis. In vitro data suggest that this is not due to cytotoxicity, but rather is due to impairment of invasive capacity of the cells. Further, using an in vitro model of EMT, we show that nitrofen interferes with the process of EMT and promotes mesenchymal to epithelial transformation. In addition, we show that three of the nitrofen analogues significantly reduced invasive potential of TNBC cells, which may, at least partially, be attributed to the analogues' ability to promote mesenchymal to epithelial-like transformation of TNBC cells. Our study shows that nitrofen, and more importantly its analogues, are significantly effective in limiting the invasive potential of TNBC cell lines with minimal cytotoxic effect. Further, we demonstrate that nitrofen its analogues, are very effective in reversing mesenchymal phenotype to a more epithelial-like phenotype. This may be significant for the treatment of patients with mesenchymal-TNBC tumor subtype who are well known to exhibit high resistance to chemotherapy.
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Affiliation(s)
- Elizabeth Garcia
- Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, 3-020R Katz Group Centre for Pharmacy and Health Research, Edmonton, AB, T6G 2E1, Canada
| | - Ismat Luna
- Department of Chemistry, Faculty of Science, University of Alberta, Edmonton, Canada
| | - Kaya L Persad
- Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, 3-020R Katz Group Centre for Pharmacy and Health Research, Edmonton, AB, T6G 2E1, Canada
| | - Kate Agopsowicz
- Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
| | - David A Jay
- Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, 3-020R Katz Group Centre for Pharmacy and Health Research, Edmonton, AB, T6G 2E1, Canada
| | - Frederick G West
- Department of Chemistry, Faculty of Science, University of Alberta, Edmonton, Canada
| | - Mary M Hitt
- Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
| | - Sujata Persad
- Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, 3-020R Katz Group Centre for Pharmacy and Health Research, Edmonton, AB, T6G 2E1, Canada.
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Nguyen HT, Kacimi SEO, Nguyen TL, Suman KH, Lemus-Martin R, Saleem H, Do DN. MiR-21 in the Cancers of the Digestive System and Its Potential Role as a Diagnostic, Predictive, and Therapeutic Biomarker. BIOLOGY 2021; 10:biology10050417. [PMID: 34066762 PMCID: PMC8151274 DOI: 10.3390/biology10050417] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/27/2021] [Accepted: 05/03/2021] [Indexed: 12/12/2022]
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs. They can regulate the expression of their target genes, and thus, their dysregulation significantly contributes to the development of cancer. Growing evidence suggests that miRNAs could be used as cancer biomarkers. As an oncogenic miRNA, the roles of miR-21 as a diagnostic and prognostic biomarker, and its therapeutic applications have been extensively studied. In this review, the roles of miR-21 are first demonstrated via its different molecular networks. Then, a comprehensive review on the potential targets and the current applications as a diagnostic and prognostic cancer biomarker and the therapeutic roles of miR-21 in six different cancers in the digestive system is provided. Lastly, a brief discussion on the challenges for the use of miR-21 as a therapeutic tool for these cancers is added.
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Affiliation(s)
- Ha Thi Nguyen
- Institute of Research and Development, Duy Tan University, Danang 550000, Vietnam;
- Faculty of Medicine, Duy Tan University, Danang 550000, Vietnam
| | | | - Truc Ly Nguyen
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea;
| | - Kamrul Hassan Suman
- Department of Fisheries Biology & Aquatic Environment, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur 1706, Bangladesh;
| | | | - Humaira Saleem
- Jamil–ur–Rahman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;
| | - Duy Ngoc Do
- Department of Animal Science and Aquaculture, Dalhousie University, Truro, NS B2N5E3, Canada
- Correspondence: ; Tel.: +1-819-571-5310
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Song K, Farzaneh M. Signaling pathways governing breast cancer stem cells behavior. Stem Cell Res Ther 2021; 12:245. [PMID: 33863385 PMCID: PMC8052733 DOI: 10.1186/s13287-021-02321-w] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 03/31/2021] [Indexed: 02/06/2023] Open
Abstract
Breast cancer is the second common cancer and the leading cause of malignancy among females overall. Breast cancer stem cells (BCSCs) are a small population of breast cancer cells that play a critical role in the metastasis of breast cancer to other organs in the body. BCSCs have both self-renewal and differentiation capacities, which are thought to contribute to the aggressiveness of metastatic lesions. Therefore, targeting BCSCs can be a suitable approach for the treatment and metastasis of breast cancer. Growing evidence has indicated that the Wnt, NFκB, Notch, BMP2, STAT3, and hedgehog (Hh) signaling pathways govern epithelial-to-mesenchymal transition (EMT) activation, growth, and tumorigenesis of BCSCs in the primary regions. miRNAs as the central regulatory molecules also play critical roles in BCSC self-renewal, metastasis, and drug resistance. Hence, targeting these pathways might be a novel therapeutic approach for breast cancer diagnosis and therapy. This review discusses known signaling mechanisms involved in the stimulation or prevention of BCSC self-renewal, metastasis, and tumorigenesis.
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Affiliation(s)
- Kai Song
- Xuzhou Vocational College of Bioengineering, Xuzhou, 221006, Jiangsu, China.
| | - Maryam Farzaneh
- Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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35
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Humphries B, Wang Z, Yang C. MicroRNA Regulation of Breast Cancer Stemness. Int J Mol Sci 2021; 22:3756. [PMID: 33916548 PMCID: PMC8038508 DOI: 10.3390/ijms22073756] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 04/01/2021] [Accepted: 04/02/2021] [Indexed: 12/22/2022] Open
Abstract
Recent advances in our understanding of breast cancer have demonstrated that cancer stem-like cells (CSCs, also known as tumor-initiating cell (TICs)) are central for progression and recurrence. CSCs are a small subpopulation of cells present in breast tumors that contribute to growth, metastasis, therapy resistance, and recurrence, leading to poor clinical outcome. Data have shown that cancer cells can gain characteristics of CSCs, or stemness, through alterations in key signaling pathways. The dysregulation of miRNA expression and signaling have been well-documented in cancer, and recent studies have shown that miRNAs are associated with breast cancer initiation, progression, and recurrence through regulating CSC characteristics. More specifically, miRNAs directly target central signaling nodes within pathways that can drive the formation, maintenance, and even inhibition of the CSC population. This review aims to summarize these research findings specifically in the context of breast cancer. This review also discusses miRNAs as biomarkers and promising clinical therapeutics, and presents a comprehensive summary of currently validated targets involved in CSC-specific signaling pathways in breast cancer.
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Affiliation(s)
- Brock Humphries
- Center for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA
| | - Zhishan Wang
- Division of Cancer Biology, Department of Medicine, MetroHealth Medical Center, Case Western Reserve University School of Medicine, 2500 MetroHealth Drive, Cleveland, OH 44109, USA;
| | - Chengfeng Yang
- Division of Cancer Biology, Department of Medicine, MetroHealth Medical Center, Case Western Reserve University School of Medicine, 2500 MetroHealth Drive, Cleveland, OH 44109, USA;
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36
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Jafari A, Babajani A, Abdollahpour-Alitappeh M, Ahmadi N, Rezaei-Tavirani M. Exosomes and cancer: from molecular mechanisms to clinical applications. Med Oncol 2021; 38:45. [PMID: 33743101 DOI: 10.1007/s12032-021-01491-0] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 03/04/2021] [Indexed: 12/15/2022]
Abstract
Exosomes are extracellular nanovesicles secreted from almost all types of normal and cancer cells. Collective evidence suggests that exosomes participate in cell-cell communication via transmitting their cargo, including nucleic acids, proteins, and metabolites to recipient cells. Tumor-derived exosomes (TEXs) play prominent roles in the regulation of molecular pathways in malignancies. Internalization of exosomes by tumor cells affects cellular pathways and several cancer hallmarks, including reprogramming of stromal cells, modulating immune responses, reconstructing extracellular matrix architecture, or even endowing tumor cells with drug features resistance. The unique biogenesis pathways of exosomes, their composition, low immunogenicity, and nontoxicity, together with their ability to target tumor cells, bring them up as an attractive vesicles for cancer therapy. Thus, understanding the molecular mechanisms of exosomes' participation in tumorigenesis will be critical for the next generation of cancer therapeutics. This review aims to summarize the exosomes' roles in different mechanisms underlying cancer progression for the rational design of tailored strategies against this illness. The present study also highlights the new findings on using these smart vesicles as therapeutic targets and potential biomarkers. Recent advances in exosome biology will open up new, more effective, less invasive, and more individualized clinical applications for treating cancer patients.
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Affiliation(s)
- Ameneh Jafari
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amirhesam Babajani
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Nayebali Ahmadi
- Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Proteomics Research Center, Department of Medical Lab Technology, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mostafa Rezaei-Tavirani
- Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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37
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Li J, Ren H, Wang J, Zhang P, Shi X. Extracellular HMGB1 promotes CD44 expression in hepatocellular carcinoma via regulating miR-21. Aging (Albany NY) 2021; 13:8380-8395. [PMID: 33661757 PMCID: PMC8034936 DOI: 10.18632/aging.202649] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 10/12/2020] [Indexed: 04/11/2023]
Abstract
As a member of damage-associated molecular patterns (DAMPs), extracellular high-mobility group box 1 (HMGB1) plays a critical role in hepatocellular carcinoma (HCC) progression. Cluster differentiation 44 (CD44) has been demonstrated to participate in HCC progression. However, the relationship between extracellular HMGB1 and CD44 remains unclear. In this study, our results indicated that extracellular HMGB1 promoted the invasion, sphere formation and EMT process of HCC by increasing CD44 expression, which was dependent on miR-21. Moreover, miR-21 upregulated CD44 expression via activating OCT4/TGF-β1 signaling. Finally, we demonstrated the activation of Rage/JNK signaling caused by extracellular HMGB1 was responsible for miR-21 overexpression. Together, these findings reveal an important role of extracellular HMGB1 in HCC progression through upregulating miR-21/CD44.
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Affiliation(s)
- Jun Li
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Haozhen Ren
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Jinglin Wang
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Pengfei Zhang
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Xiaolei Shi
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
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38
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LncRNAs and microRNAs as Essential Regulators of Stemness in Breast Cancer Stem Cells. Biomolecules 2021; 11:biom11030380. [PMID: 33802575 PMCID: PMC7998729 DOI: 10.3390/biom11030380] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 02/13/2021] [Accepted: 02/22/2021] [Indexed: 12/24/2022] Open
Abstract
Breast cancer is an aggressive disease with a high incidence in women worldwide. Two decades ago, a controversial hypothesis was proposed that cancer arises from a subpopulation of “tumor initiating cells” or “cancer stem cells-like” (CSC). Today, CSC are defined as small subset of somatic cancer cells within a tumor with self-renewal properties driven by the aberrant expression of genes involved in the maintenance of a stemness-like phenotype. The understanding of the underlying cellular and molecular mechanisms involved in the maintenance of CSC subpopulation are fundamental in the development and persistence of breast cancer. Nowadays, the hypothesis suggests that genetic and epigenetic alterations give rise to breast cancer stem cells (bCSC), which are responsible for self-renewal, tumor growth, chemoresistance, poor prognosis and low survival in patients. However, the prominence of bCSC, as well as the molecular mechanisms that regulates and promotes the malignant phenotypes, are still poorly understood. The role of non-coding RNAs (ncRNAs), such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) acting as oncogenes or tumor suppressor genes has been recently highlighted by a plethora of studies in breast cancer. These ncRNAs positively or negatively impact on different signaling pathways that govern the cancer hallmarks associated with bCSC, making them attractive targets for therapy. In this review, we present a current summary of the studies on the pivotal roles of lncRNAs and microRNAs in the regulation of genes associated to stemness of bCSC.
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40
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Small in Size, but Large in Action: microRNAs as Potential Modulators of PTEN in Breast and Lung Cancers. Biomolecules 2021; 11:biom11020304. [PMID: 33670518 PMCID: PMC7922700 DOI: 10.3390/biom11020304] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 02/15/2021] [Accepted: 02/15/2021] [Indexed: 12/17/2022] Open
Abstract
MicroRNAs (miRNAs) are well-known regulators of biological mechanisms with a small size of 19–24 nucleotides and a single-stranded structure. miRNA dysregulation occurs in cancer progression. miRNAs can function as tumor-suppressing or tumor-promoting factors in cancer via regulating molecular pathways. Breast and lung cancers are two malignant thoracic tumors in which the abnormal expression of miRNAs plays a significant role in their development. Phosphatase and tensin homolog (PTEN) is a tumor-suppressor factor that is capable of suppressing the growth, viability, and metastasis of cancer cells via downregulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling. PTEN downregulation occurs in lung and breast cancers to promote PI3K/Akt expression, leading to uncontrolled proliferation, metastasis, and their resistance to chemotherapy and radiotherapy. miRNAs as upstream mediators of PTEN can dually induce/inhibit PTEN signaling in affecting the malignant behavior of lung and breast cancer cells. Furthermore, long non-coding RNAs and circular RNAs can regulate the miRNA/PTEN axis in lung and breast cancer cells. It seems that anti-tumor compounds such as baicalein, propofol, and curcumin can induce PTEN upregulation by affecting miRNAs in suppressing breast and lung cancer progression. These topics are discussed in the current review with a focus on molecular pathways.
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41
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Arisan ED, Rencuzogullari O, Cieza-Borrella C, Miralles Arenas F, Dwek M, Lange S, Uysal-Onganer P. MiR-21 Is Required for the Epithelial-Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells. Int J Mol Sci 2021; 22:1557. [PMID: 33557112 PMCID: PMC7913884 DOI: 10.3390/ijms22041557] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/27/2021] [Accepted: 02/01/2021] [Indexed: 12/15/2022] Open
Abstract
Breast cancer (BCa) is one of the leading health problems among women. Although significant achievements have led to advanced therapeutic success with targeted therapy options, more efforts are required for different subtypes of tumors and according to genomic, transcriptomic, and proteomic alterations. This study underlines the role of microRNA-21 (miR-21) in metastatic MDA-MB-231 breast cancer cells. Following the knockout of miR-21 from MDA-MB-231 cells, which have the highest miR-21 expression levels compared to MCF-7 and SK-BR-3 BCa cells, a decrease in epithelial-mesenchymal transition (EMT) via downregulation of mesenchymal markers was observed. Wnt-11 was a critical target for miR-21, and the Wnt-11 related signaling axis was altered in the stable miR-21 knockout cells. miR-21 expression was associated with a significant increase in mesenchymal markers in MDA-MB-231 BCa cells. Furthermore, the release of extracellular vesicles (EVs) was significantly reduced in the miR-21 KO cells, alongside a significant reduction in relative miR-21 export in EV cargo, compared with control cells. We conclude that miR-21 is a leading factor involved in mesenchymal transition in MDA-MB-231 BCa. Future therapeutic strategies could focus on its role in the treatment of metastatic breast cancer.
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Affiliation(s)
- Elif Damla Arisan
- Institute of Biotechnology, Gebze Technical University, Gebze, 41400 Kocaeli, Turkey;
| | - Ozge Rencuzogullari
- Department of Molecular Biology and Genetics, Atakoy Campus, Istanbul Kultur University, 34156 Istanbul, Turkey;
| | - Clara Cieza-Borrella
- Centre for Biomedical Education/Cell Biology and Genetics Research Centre, St. George’s, University of London, Cranmer Terrace, London SW17 0RE, UK; (C.C.-B.); (F.M.A.)
| | - Francesc Miralles Arenas
- Centre for Biomedical Education/Cell Biology and Genetics Research Centre, St. George’s, University of London, Cranmer Terrace, London SW17 0RE, UK; (C.C.-B.); (F.M.A.)
| | - Miriam Dwek
- Cancer Research Group, School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK;
| | - Sigrun Lange
- Tissue Architecture and Regeneration Research Group, School of Life Sciences, University of Westminster, London W1W 6UW, UK;
| | - Pinar Uysal-Onganer
- Cancer Research Group, School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK;
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MicroRNA regulation of cancer stem cells in the pathogenesis of breast cancer. Cancer Cell Int 2021; 21:31. [PMID: 33413418 PMCID: PMC7792222 DOI: 10.1186/s12935-020-01716-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 12/07/2020] [Accepted: 12/16/2020] [Indexed: 02/06/2023] Open
Abstract
Breast cancer is the most common cancer among women and accounts for 30% of all female malignancies worldwide. Breast cancer stem cells (BCSCs) are a small population of breast cancer cells that exhibit multiple characteristics including differentiation capacity, self-renewal and therapeutic resistance. Recently, BCSCs have attracted attention due to their modulation of breast tumor behaviors and drug resistance. miRNAs are small noncoding mRNAs involved in virtually all biological processes, including stem cell development, maintenance and differentiation. In breast cancer, miRNAs appear to be multi-faceted since they can act as either suppressors or oncogenes to regulate breast cancer progression. This review summarizes the critical roles of miRNAs in regulating multiple signaling pathways such as Wnt/β-catenin, Notch, PI3K/AKT/mTOR, BMI-1 and STAT3 that are important for the BCSC maintenance.
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Rossi F, Noren H, Jove R, Beljanski V, Grinnemo KH. Differences and similarities between cancer and somatic stem cells: therapeutic implications. Stem Cell Res Ther 2020; 11:489. [PMID: 33208173 PMCID: PMC7672862 DOI: 10.1186/s13287-020-02018-6] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 11/05/2020] [Indexed: 02/06/2023] Open
Abstract
Over the last decades, the cancer survival rate has increased due to personalized therapies, the discovery of targeted therapeutics and novel biological agents, and the application of palliative treatments. Despite these advances, tumor resistance to chemotherapy and radiation and rapid progression to metastatic disease are still seen in many patients. Evidence has shown that cancer stem cells (CSCs), a sub-population of cells that share many common characteristics with somatic stem cells (SSCs), contribute to this therapeutic failure. The most critical properties of CSCs are their self-renewal ability and their capacity for differentiation into heterogeneous populations of cancer cells. Although CSCs only constitute a low percentage of the total tumor mass, these cells can regrow the tumor mass on their own. Initially identified in leukemia, CSCs have subsequently been found in cancers of the breast, the colon, the pancreas, and the brain. Common genetic and phenotypic features found in both SSCs and CSCs, including upregulated signaling pathways such as Notch, Wnt, Hedgehog, and TGF-β. These pathways play fundamental roles in the development as well as in the control of cell survival and cell fate and are relevant to therapeutic targeting of CSCs. The differences in the expression of membrane proteins and exosome-delivered microRNAs between SSCs and CSCs are also important to specifically target the stem cells of the cancer. Further research efforts should be directed toward elucidation of the fundamental differences between SSCs and CSCs to improve existing therapies and generate new clinically relevant cancer treatments.
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Affiliation(s)
- Fiorella Rossi
- NSU Cell Therapy Institute, Nova Southeastern University, 3301 College Ave, 3200 South University Drive, Fort Lauderdale, FL, 33328, USA
| | - Hunter Noren
- NSU Cell Therapy Institute, Nova Southeastern University, 3301 College Ave, 3200 South University Drive, Fort Lauderdale, FL, 33328, USA
| | - Richard Jove
- NSU Cell Therapy Institute, Nova Southeastern University, 3301 College Ave, 3200 South University Drive, Fort Lauderdale, FL, 33328, USA
| | - Vladimir Beljanski
- NSU Cell Therapy Institute, Nova Southeastern University, 3301 College Ave, 3200 South University Drive, Fort Lauderdale, FL, 33328, USA.
| | - Karl-Henrik Grinnemo
- NSU Cell Therapy Institute, Nova Southeastern University, 3301 College Ave, 3200 South University Drive, Fort Lauderdale, FL, 33328, USA. .,Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. .,Department of Surgical Sciences, Division of Cardiothoracic Surgery and Anaesthesiology, Uppsala University, Akademiska University Hospital, Akademiska sjukhuset, ingång 50, 4 tr, 751 85, Uppsala, Sweden.
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Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals. Molecules 2020; 25:molecules25204701. [PMID: 33066509 PMCID: PMC7587345 DOI: 10.3390/molecules25204701] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/08/2020] [Accepted: 10/13/2020] [Indexed: 02/06/2023] Open
Abstract
Cancer is a global health concern and one of the main causes of disease-related death. Even with considerable progress in investigations on cancer therapy, effective anti-cancer agents and regimens have thus far been insufficient. There has been compelling evidence that natural phytochemicals and their derivatives have potent anti-cancer activities. Plant-based anti-cancer agents, such as etoposide, irinotecan, paclitaxel, and vincristine, are currently being applied in medical treatments for patients with cancer. Further, the efficacy of plenty of phytochemicals has been evaluated to discover a promising candidate for cancer therapy. For developing more effective cancer therapy, it is required to apprehend the molecular mechanism deployed by natural compounds. MicroRNAs (miRNAs) have been realized to play a pivotal role in regulating cellular signaling pathways, affecting the efficacy of therapeutic agents in cancer. This review presents a feature of phytochemicals with anti-cancer activity, focusing mainly on the relationship between phytochemicals and miRNAs, with insights into the role of miRNAs as the mediators and the regulators of anti-cancer effects of phytochemicals.
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Liu C, Zhao Q, Yu X. Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer. Front Oncol 2020; 10:561595. [PMID: 33123472 PMCID: PMC7566900 DOI: 10.3389/fonc.2020.561595] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 08/27/2020] [Indexed: 02/05/2023] Open
Abstract
Accumulating discoveries highlight the importance of interaction between marrow stromal cells and cancer cells for bone metastasis. Bone is the most common metastatic site of breast cancer and bone marrow adipocytes (BMAs) are the most abundant component of the bone marrow microenvironment. BMAs are unique in their origin and location, and recently they are found to serve as an endocrine organ that secretes adipokines, cytokines, chemokines, and growth factors. It is reasonable to speculate that BMAs contribute to the modification of bone metastatic microenvironment and affecting metastatic breast cancer cells in the bone marrow. Indeed, BMAs may participate in bone metastasis of breast cancer through regulation of recruitment, invasion, survival, colonization, proliferation, angiogenesis, and immune modulation by their production of various adipocytokines. In this review, we provide an overview of research progress, focusing on adipocytokines secreted by BMAs and their potential roles for bone metastasis of breast cancer, and investigating the mechanisms mediating the interaction between BMAs and metastatic breast cancer cells. Based on current findings, BMAs may function as a pivotal modulator of bone metastasis of breast cancer, therefore targeting BMAs combined with conventional treatment programs might present a promising therapeutic option.
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Affiliation(s)
- Chang Liu
- Department of Endocrinology and Metabolism, Laboratory of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Qian Zhao
- Department of Endocrinology and Metabolism, Laboratory of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.,Department of General Practice, West China Hospital, Sichuan University, Chengdu, China
| | - Xijie Yu
- Department of Endocrinology and Metabolism, Laboratory of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
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Zheng X, Dong L, Zhao S, Li Q, Liu D, Zhu X, Ge X, Li R, Wang G. Propofol Affects Non-Small-Cell Lung Cancer Cell Biology By Regulating the miR-21/PTEN/AKT Pathway In Vitro and In Vivo. Anesth Analg 2020; 131:1270-1280. [PMID: 32925348 DOI: 10.1213/ane.0000000000004778] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Propofol is a common sedative-hypnotic drug traditionally used for inducing and maintaining general anesthesia. Recent studies have drawn attention to the nonanesthetic effects of propofol, but the potential mechanism by which propofol suppresses non-small-cell lung cancer (NSCLC) progression has not been fully elucidated. METHODS For the in vitro experiments, we used propofol (0, 2, 5, and 10 µg/mL) to treat A549 cells for 1, 4, and 12 hours and Cell Counting Kit-8 (CCK-8) to detect proliferation. Apoptosis was measured with flow cytometry. We also transfected A549 cells with an microribonucleic acid-21 (miR-21) mimic or negative control ribonucleic acid (RNA) duplex and phosphatase and tensin homolog, deleted on chromosome 10 (PTEN) small interfering ribonucleic acid (siRNA) or negative control. PTEN, phosphorylated protein kinase B (pAKT), and protein kinase B (AKT) expression were detected using Western blotting, whereas miR-21 expression was examined by real-time polymerase chain reaction (RT-PCR). In vivo, nude mice were given injections of A549 cells to grow xenograft tumors; 8 days later, the mice were intraperitoneally injected with propofol (35 mg/kg) or soybean oil. Tumors were then collected from mice and analyzed by immunohistochemistry and Western blotting. RESULTS Propofol inhibited growth (1 hour, P = .001; 4 hours, P ≤ .0001; 12 hours, P = .0004) and miR-21 expression (P ≤ .0001) and induced apoptosis (1 hour, P = .0022; 4 hours, P = .0005; 12 hours, P ≤ .0001) in A549 cells in a time and concentration-dependent manner. MiR-21 mimic and PTEN siRNA transfection antagonized the suppressive effects of propofol on A549 cells by decreasing PTEN protein expression (mean differences [MD] [95% confidence interval {CI}], -0.51 [-0.86 to 0.16], P = .0058; MD [95% CI], 0.81 [0.07-1.55], P = .0349, respectively), resulting in an increase in pAKT levels (MD [95% CI] = -0.82 [-1.46 to -0.18], P = .0133) following propofol exposure. In vivo, propofol treatment reduced NSCLC tumor growth (MD [95% CI] = -109.47 [-167.03 to -51.91], P ≤ .0001) and promoted apoptosis (MD [95% CI] = 38.53 [11.69-65.36], P = .0093). CONCLUSIONS Our study indicated that propofol inhibited A549 cell growth, accelerated apoptosis via the miR-21/PTEN/AKT pathway in vitro, suppressed NSCLC tumor cell growth, and promoted apoptosis in vivo. Our findings provide new implications for propofol in cancer therapy and indicate that propofol is extremely advantageous in surgical treatment.
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Affiliation(s)
- Xiaoyu Zheng
- From the Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Linlin Dong
- Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China
| | - Su Zhao
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Quanyi Li
- From the Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Dandan Liu
- From the Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Xidong Zhu
- From the Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Xiaona Ge
- From the Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Ruzhe Li
- From the Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Guonian Wang
- From the Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China
- Department of Anesthesiology, Pain Research Institute of Heilongjiang Academy of Medical Sciences, Harbin, China
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Alemohammad H, Asadzadeh Z, Motafakker Azad R, Hemmat N, Najafzadeh B, Vasefifar P, Najafi S, Baradaran B. Signaling pathways and microRNAs, the orchestrators of NANOG activity during cancer induction. Life Sci 2020; 260:118337. [PMID: 32841661 DOI: 10.1016/j.lfs.2020.118337] [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] [Received: 07/08/2020] [Revised: 08/18/2020] [Accepted: 08/20/2020] [Indexed: 12/12/2022]
Abstract
Cancer stem cells (CSCs) are a small part of cancer cells inside the tumor that have similar characteristics to normal stem cells. CSCs stimulate tumor initiation and progression in a variety of cancers. Several transcription factors such as NANOG, SOX2, and OCT4 maintain the characteristics of CSCs and their upregulation is seen in many malignancies resulting in increased metastasis, invasion, and recurrence. Among these factors, NANOG plays an important role in regulating the self-renewal and pluripotency of CSCs and the clinical significance of NANOG has been suggested as a marker of CSCs in many cancers. The up and down-regulation of NANOG is associated with several important signaling pathways, including JAK/STAT, Wnt/β-catenin, Notch, TGF-β, Hedgehog, and several microRNAs (miRNAs). In this review, we will investigate the function of NANOG in CSCs and the molecular mechanism of its regulation by signaling pathways and miRNAs. We will also investigate targeting NANOG with different techniques, which is a promising treatment strategy for cancer treatment.
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Affiliation(s)
- Hajar Alemohammad
- Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Zahra Asadzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Nima Hemmat
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Basira Najafzadeh
- Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Parisa Vasefifar
- Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Souzan Najafi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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Wong JS, Cheah YK. Potential miRNAs for miRNA-Based Therapeutics in Breast Cancer. Noncoding RNA 2020; 6:E29. [PMID: 32668603 PMCID: PMC7549352 DOI: 10.3390/ncrna6030029] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Revised: 07/04/2020] [Accepted: 07/07/2020] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that can post-transcriptionally regulate the genes involved in critical cellular processes. The aberrant expressions of oncogenic or tumor suppressor miRNAs have been associated with cancer progression and malignancies. This resulted in the dysregulation of signaling pathways involved in cell proliferation, apoptosis and survival, metastasis, cancer recurrence and chemoresistance. In this review, we will first (i) provide an overview of the miRNA biogenesis pathways, and in vitro and in vivo models for research, (ii) summarize the most recent findings on the roles of microRNAs (miRNAs) that could potentially be used for miRNA-based therapy in the treatment of breast cancer and (iii) discuss the various therapeutic applications.
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Affiliation(s)
- Jun Sheng Wong
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
| | - Yoke Kqueen Cheah
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia
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Forterre A, Komuro H, Aminova S, Harada M. A Comprehensive Review of Cancer MicroRNA Therapeutic Delivery Strategies. Cancers (Basel) 2020; 12:E1852. [PMID: 32660045 PMCID: PMC7408939 DOI: 10.3390/cancers12071852] [Citation(s) in RCA: 133] [Impact Index Per Article: 26.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 07/06/2020] [Accepted: 07/07/2020] [Indexed: 12/12/2022] Open
Abstract
In the field of molecular oncology, microRNAs (miRNAs) and their role in regulating physiological processes and cancer pathogenesis have been a revolutionary discovery over the last decade. It is now considered that miRNA dysregulation influences critical molecular pathways involved in tumor progression, invasion, angiogenesis and metastasis in a wide range of cancer types. Hence, altering miRNA levels in cancer cells has promising potential as a therapeutic intervention, which is discussed in many other articles in this Special Issue. Some of the most significant hurdles in therapeutic miRNA usage are the stability and the delivery system. In this review, we cover a comprehensive update on the challenges and strategies for the development of therapeutic miRNA delivery systems that includes virus-based delivery, non-viral delivery (artificial lipid-based vesicles, polymer-based or chemical structures), and recently emerged extracellular vesicle (EV)-based delivery systems.
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Affiliation(s)
- Alexis Forterre
- UMR DIATHEC, EA 7294, Centre Européen d’Etude du Diabète, 67200 Strasbourg, France;
| | - Hiroaki Komuro
- Department of Cardiovascular Physiology, Tokyo Medical and Dental University, Tokyo 113-8510, Japan;
| | - Shakhlo Aminova
- Lyman Briggs College, Michigan State University, East Lansing, MI 48825, USA;
- Institute for Quantitative Health Sciences and Engineering (IQ), Michigan State University, East Lansing, MI 48824, USA
| | - Masako Harada
- Institute for Quantitative Health Sciences and Engineering (IQ), Michigan State University, East Lansing, MI 48824, USA
- Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA
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Kim H, Lee S, Shin E, Seong KM, Jin YW, Youn H, Youn B. The Emerging Roles of Exosomes as EMT Regulators in Cancer. Cells 2020; 9:cells9040861. [PMID: 32252322 PMCID: PMC7226841 DOI: 10.3390/cells9040861] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 03/28/2020] [Accepted: 03/31/2020] [Indexed: 02/06/2023] Open
Abstract
Epithelial–mesenchymal transition (EMT) causes epithelial cells to lose their polarity and adhesion property, and endows them with migratory and invasive properties to enable them to become mesenchymal stem cells. EMT occurs throughout embryonic development, during wound healing, and in various pathological processes, including tumor progression. Considerable research in the last few decades has revealed that EMT is invariably related to tumor aggressiveness and metastasis. Apart from the interactions between numerous intracellular signaling pathways known to regulate EMT, extracellular modulators in the tumor microenvironment also influence tumor cells to undergo EMT, with extracellular vesicles (EVs) receiving increasing attention as EMT inducers. EVs comprise exosomes and microvesicles that carry proteins, nucleic acids, lipids, and other small molecules to stimulate EMT in cells. Among EVs, exosomes have been investigated in many studies, and their role has been found to be significant with respect to regulating intercellular communications. In this review, we summarize recent studies on exosomes and their cargoes that induce cancer-associated EMT. Furthermore, we describe the possible applications of exosomes as promising therapeutic strategies.
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Affiliation(s)
- Hyunwoo Kim
- Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea; (H.K.); (S.L.); (E.S.)
| | - Sungmin Lee
- Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea; (H.K.); (S.L.); (E.S.)
| | - Eunguk Shin
- Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea; (H.K.); (S.L.); (E.S.)
| | - Ki Moon Seong
- Laboratory of Low Dose Risk Assessment, National Radiation Emergency Medical Center, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Korea; (K.M.S.); (Y.W.J.)
| | - Young Woo Jin
- Laboratory of Low Dose Risk Assessment, National Radiation Emergency Medical Center, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Korea; (K.M.S.); (Y.W.J.)
| | - HyeSook Youn
- Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul 05006, Korea
- Correspondence: (H.Y.); (B.Y.); Tel.: +82-2-6935-2438 (H.Y.); +82-51-510-2264 (B.Y.); Fax: +82-2-3408-4334 (H.Y.); +82-51-581-2962 (B.Y.)
| | - BuHyun Youn
- Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea; (H.K.); (S.L.); (E.S.)
- Department of Biological Sciences, Pusan National University, Busan 46241, Korea
- Correspondence: (H.Y.); (B.Y.); Tel.: +82-2-6935-2438 (H.Y.); +82-51-510-2264 (B.Y.); Fax: +82-2-3408-4334 (H.Y.); +82-51-581-2962 (B.Y.)
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