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1
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Beigi A, Naghib SM, Matini A, Tajabadi M, Mozafari MR. Lipid-Based Nanocarriers for Targeted Gene Delivery in Lung Cancer Therapy: Exploring a Novel Therapeutic Paradigm. Curr Gene Ther 2025; 25:92-112. [PMID: 38778601 DOI: 10.2174/0115665232292768240503050508] [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: 11/14/2023] [Revised: 03/28/2024] [Accepted: 04/03/2024] [Indexed: 05/25/2024]
Abstract
Lung cancer is a significant cause of cancer-related death worldwide. It can be broadly categorised into small-cell lung cancer (SCLC) and Non-small cell lung cancer (NSCLC). Surgical intervention, radiation therapy, and the administration of chemotherapeutic medications are among the current treatment modalities. However, the application of chemotherapy may be limited in more advanced stages of metastasis due to the potential for adverse effects and a lack of cell selectivity. Although small-molecule anticancer treatments have demonstrated effectiveness, they still face several challenges. The challenges at hand in this context comprise insufficient solubility in water, limited bioavailability at specific sites, adverse effects, and the requirement for epidermal growth factor receptor inhibitors that are genetically tailored. Bio-macromolecular drugs, including small interfering RNA (siRNA) and messenger RNA (mRNA), are susceptible to degradation when exposed to the bodily fluids of humans, which can reduce stability and concentration. In this context, nanoscale delivery technologies are utilised. These agents offer encouraging prospects for the preservation and regulation of pharmaceutical substances, in addition to improving the solubility and stability of medications. Nanocarrier-based systems possess the notable advantage of facilitating accurate and sustained drug release, as opposed to traditional systemic methodologies. The primary focus of scientific investigation has been to augment the therapeutic efficacy of nanoparticles composed of lipids. Numerous nanoscale drug delivery techniques have been implemented to treat various respiratory ailments, such as lung cancer. These technologies have exhibited the potential to mitigate the limitations associated with conventional therapy. As an illustration, applying nanocarriers may enhance the solubility of small-molecule anticancer drugs and prevent the degradation of bio-macromolecular drugs. Furthermore, these devices can administer medications in a controlled and extended fashion, thereby augmenting the therapeutic intervention's effectiveness and reducing adverse reactions. However, despite these promising results, challenges remain that must be addressed. Multiple factors necessitate consideration when contemplating the application of nanoparticles in medical interventions. To begin with, the advancement of more efficient delivery methods is imperative. In addition, a comprehensive investigation into the potential toxicity of nanoparticles is required. Finally, additional research is needed to comprehend these treatments' enduring ramifications. Despite these challenges, the field of nanomedicine demonstrates considerable promise in enhancing the therapy of lung cancer and other respiratory diseases.
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Affiliation(s)
- Anahita Beigi
- Nanotechnology Department, School of Advanced Technologies, Iran University of Science and Technology, Tehran, Iran
| | - Seyed Morteza Naghib
- Nanotechnology Department, School of Advanced Technologies, Iran University of Science and Technology, Tehran, Iran
| | - Amir Matini
- Nanotechnology Department, School of Advanced Technologies, Iran University of Science and Technology, Tehran, Iran
| | - Maryam Tajabadi
- School of Metallurgy and Materials Engineering, Iran University of Science and Technology (IUST), Narmak, Tehran, 16844, Iran
| | - Mohammad Reza Mozafari
- Australasian Nanoscience and Nanotechnology Initiative (ANNI), Monash University LPO, Clayton, VIC 3168, Australia
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2
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Relationship Between the MicroRNAs and PI3K/AKT/mTOR Axis: Focus on Non-Small Cell Lung Cancer. Pathol Res Pract 2022; 239:154093. [DOI: 10.1016/j.prp.2022.154093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/19/2022] [Accepted: 08/23/2022] [Indexed: 11/21/2022]
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Gong Z, Huang W, Wang B, Liang N, Long S, Li W, Zhou Q. Interplay between cyclooxygenase‑2 and microRNAs in cancer (Review). Mol Med Rep 2021; 23:347. [PMID: 33760116 PMCID: PMC7974460 DOI: 10.3892/mmr.2021.11986] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 02/23/2021] [Indexed: 02/06/2023] Open
Abstract
Tumor‑associated inflammation and aberrantly expressed biomarkers have been demonstrated to play crucial roles in the cancer microenvironment. Cyclooxygenase‑2 (COX‑2), a prominent inflammatory factor, is highly expressed in tumor cells and contributes to tumor growth, recurrence and metastasis. Overexpression of COX‑2 may occur at both transcriptional and post‑transcriptional levels. Thus, an improved understanding of the regulatory mechanisms of COX‑2 can facilitate the development of novel antitumor therapies. MicroRNAs (miRNAs) are a group of small non‑coding RNAs that act as translation repressors of target mRNAs, and play vital roles in regulating cancer development and progression. The present review discusses the association between miRNAs and COX‑2 expression in different types of cancer. Understanding the regulatory role of miRNAs in COX‑2 post‑transcription can provide novel insight for suppressing COX‑2 expression via gene silencing mechanisms, which offer new perspectives and future directions for the development of novel COX‑2 selective inhibitors based on miRNAs.
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Affiliation(s)
- Zexiong Gong
- Department of Anesthesiology, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421002, P.R. China
| | - Weiguo Huang
- Cancer Research Institute, Medical College of University of South China, Hengyang, Hunan 421001, P.R. China
| | - Baiyun Wang
- Department of Anesthesiology, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421002, P.R. China
| | - Na Liang
- Department of Anesthesiology, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421002, P.R. China
| | - Songkai Long
- Department of Anesthesiology, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421002, P.R. China
| | - Wanjun Li
- Department of Anesthesiology, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421002, P.R. China
| | - Qier Zhou
- Department of Anesthesiology, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421002, P.R. China
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Pozza DH, De Mello RA, Araujo RLC, Velcheti V. MicroRNAs in Lung Cancer Oncogenesis and Tumor Suppression: How it Can Improve the Clinical Practice? Curr Genomics 2020; 21:372-381. [PMID: 33093800 PMCID: PMC7536806 DOI: 10.2174/1389202921999200630144712] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 06/10/2020] [Accepted: 06/10/2020] [Indexed: 12/18/2022] Open
Abstract
Background Lung cancer (LC) development is a process that depends on genetic mutations. The DNA methylation, an important epigenetic modification, is associated with the expression of non-coding RNAs, such as microRNAs. MicroRNAs are particularly essential for cell physiology, since they play a critical role in tumor suppressor gene activity. Furthermore, epigenetic disruptions are the primary event in cell modification, being related to tumorigenesis. In this context, microRNAs can be a useful tool in the LC suppression, consequently improving prognosis and predicting treatment. Conclusion This manuscript reviews the main microRNAs involved in LC and its potential clinical applications to improve outcomes, such as survival and better quality of life.
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Affiliation(s)
- Daniel Humberto Pozza
- 1Departamento de Biomedicina da Faculdade de Medicina, and Faculdade de Ciências da Nutrição e Alimentação, and I3s, Universidade do Porto, Porto, Portugal; 2Algarve Biomedical Centre, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal; 3Department of Clinical & Experimental Oncology, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil; 4Precision Oncology and Health Economic Group, Nine of July University, São Paulo, Brazil; 5Department of Digestive Surgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, Brazil; 6Department of Oncology, Albert Einstein Israelite Hospital, São Paulo, Brazil; 7Thoracic Oncology Program, NYU Langone, Perlmutter Cancer Center, New York, NY, 10016, USA
| | - Ramon Andrade De Mello
- 1Departamento de Biomedicina da Faculdade de Medicina, and Faculdade de Ciências da Nutrição e Alimentação, and I3s, Universidade do Porto, Porto, Portugal; 2Algarve Biomedical Centre, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal; 3Department of Clinical & Experimental Oncology, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil; 4Precision Oncology and Health Economic Group, Nine of July University, São Paulo, Brazil; 5Department of Digestive Surgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, Brazil; 6Department of Oncology, Albert Einstein Israelite Hospital, São Paulo, Brazil; 7Thoracic Oncology Program, NYU Langone, Perlmutter Cancer Center, New York, NY, 10016, USA
| | - Raphael L C Araujo
- 1Departamento de Biomedicina da Faculdade de Medicina, and Faculdade de Ciências da Nutrição e Alimentação, and I3s, Universidade do Porto, Porto, Portugal; 2Algarve Biomedical Centre, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal; 3Department of Clinical & Experimental Oncology, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil; 4Precision Oncology and Health Economic Group, Nine of July University, São Paulo, Brazil; 5Department of Digestive Surgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, Brazil; 6Department of Oncology, Albert Einstein Israelite Hospital, São Paulo, Brazil; 7Thoracic Oncology Program, NYU Langone, Perlmutter Cancer Center, New York, NY, 10016, USA
| | - Vamsidhar Velcheti
- 1Departamento de Biomedicina da Faculdade de Medicina, and Faculdade de Ciências da Nutrição e Alimentação, and I3s, Universidade do Porto, Porto, Portugal; 2Algarve Biomedical Centre, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal; 3Department of Clinical & Experimental Oncology, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil; 4Precision Oncology and Health Economic Group, Nine of July University, São Paulo, Brazil; 5Department of Digestive Surgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, Brazil; 6Department of Oncology, Albert Einstein Israelite Hospital, São Paulo, Brazil; 7Thoracic Oncology Program, NYU Langone, Perlmutter Cancer Center, New York, NY, 10016, USA
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Rzeszutek I, Singh A. Small RNAs, Big Diseases. Int J Mol Sci 2020; 21:E5699. [PMID: 32784829 PMCID: PMC7460979 DOI: 10.3390/ijms21165699] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 08/06/2020] [Accepted: 08/08/2020] [Indexed: 02/06/2023] Open
Abstract
The past two decades have seen extensive research done to pinpoint the role of microRNAs (miRNAs) that have led to discovering thousands of miRNAs in humans. It is not, therefore, surprising to see many of them implicated in a number of common as well as rare human diseases. In this review article, we summarize the progress in our understanding of miRNA-related research in conjunction with different types of cancers and neurodegenerative diseases, as well as their potential in generating more reliable diagnostic and therapeutic approaches.
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Affiliation(s)
- Iwona Rzeszutek
- Institute of Biology and Biotechnology, Department of Biotechnology, University of Rzeszow, Pigonia 1, 35-310 Rzeszow, Poland
| | - Aditi Singh
- Max Planck Institute for Developmental Biology, Max-Planck-Ring 5, 72076 Tübingen, Germany
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6
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Park N, Kang H. BMP-Induced MicroRNA-101 Expression Regulates Vascular Smooth Muscle Cell Migration. Int J Mol Sci 2020; 21:ijms21134764. [PMID: 32635504 PMCID: PMC7369869 DOI: 10.3390/ijms21134764] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 06/27/2020] [Accepted: 07/02/2020] [Indexed: 11/16/2022] Open
Abstract
Proliferation and migration of vascular smooth muscle cells (VSMCs) are implicated in blood vessel development, maintenance of vascular homeostasis, and pathogenesis of vascular disorders. MicroRNAs (miRNAs) mediate the regulation of VSMC functions in response to microenvironmental signals. Because a previous study reported that miR-101, a tumor-suppressive miRNA, is a critical regulator of cell proliferation in vascular disease, we hypothesized that miR-101 controls important cellular processes in VSMCs. The present study aimed to elucidate the effects of miR-101 on VSMC function and its molecular mechanisms. We revealed that miR-101 regulates VSMC proliferation and migration. We showed that miR-101 expression is induced by bone morphogenetic protein (BMP) signaling, and we identified dedicator of cytokinesis 4 (DOCK4) as a novel target of miR-101. Our results suggest that the BMP–miR-101–DOCK4 axis mediates the regulation of VSMC function. Our findings help further the understanding of vascular physiology and pathology.
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Affiliation(s)
- Nanju Park
- Department of Life Sciences, Incheon National University, Incheon 22012, Korea;
| | - Hara Kang
- Department of Life Sciences, Incheon National University, Incheon 22012, Korea;
- Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea
- Institute for New Drug Development, Incheon National University, Incheon 22012, Korea
- Correspondence: ; Tel.: +82-32-835-8238; Fax: +82-32-835-0763
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Sheervalilou R, Shahraki O, Hasanifard L, Shirvaliloo M, Mehranfar S, Lotfi H, Pilehvar-Soltanahmadi Y, Bahmanpour Z, Zadeh SS, Nazarlou Z, Kangarlou H, Ghaznavi H, Zarghami N. Electrochemical Nano-biosensors as Novel Approach for the Detection of Lung Cancer-related MicroRNAs. Curr Mol Med 2019; 20:13-35. [DOI: 10.2174/1566524019666191001114941] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 08/22/2019] [Accepted: 09/03/2019] [Indexed: 12/12/2022]
Abstract
In both men and women around the world, lung cancer accounts as the
principal cause of cancer-related death after breast cancer. Therefore, early detection of
the disease is a cardinal step in improving prognosis and survival of patients. Today, the
newly-defined microRNAs regulate about 30 to 60 percent of the gene expression.
Changes in microRNA Profiles are linked to numerous health conditions, making them
sophisticated biomarkers for timely, if not early, detection of cancer. Though evaluation
of microRNAs in real samples has proved to be rather challenging, which is largely
attributable to the unique characteristics of these molecules. Short length, sequence
similarity, and low concentration stand among the factors that define microRNAs.
Recently, diagnostic technologies with a focus on wide-scale point of care have recently
garnered attention as great candidates for early diagnosis of cancer. Electrochemical
nano-biosensors have recently garnered much attention as a molecular method,
showing great potential in terms of sensitivity, specificity and reproducibility, and last but
not least, adaptability to point-of-care testing. Application of nanoscale materials in
electrochemical devices as promising as it is, brings multiplexing potential for conducting
simultaneous evaluations on multiple cancer biomarkers. Thanks to their enthralling
properties, these materials can be used to improve the efficiency of cancer diagnostics,
offer more accurate predictions of prognosis, and monitor response to therapy in a more
efficacious way. This article presents a concise overview of recent advances in the
expeditiously evolving area of electrochemical biosensors for microRNA detection in
lung cancer.
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Affiliation(s)
| | - Omolbanin Shahraki
- Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Leili Hasanifard
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Milad Shirvaliloo
- Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sahar Mehranfar
- Department of Genetics and Immunology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Hajie Lotfi
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Younes Pilehvar-Soltanahmadi
- Cellular and Molecular Research Center, Research Institute for Cellular and Molecular Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Zahra Bahmanpour
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sadaf Sarraf Zadeh
- Neurosciences Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Ziba Nazarlou
- Material Engineering Department, College of Science Koç University, Istanbul 34450, Turkey
| | - Haleh Kangarlou
- Department of Physics, Urmia Branch, Islamic Azad University, Urmia, Iran
| | - Habib Ghaznavi
- Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Nosratollah Zarghami
- Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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8
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Zhang X, Li M, Sun G, Bai Y, Lv D, Liu C. MiR-563 restrains cell proliferation via targeting LIN28B in human lung cancer. Thorac Cancer 2019; 11:55-61. [PMID: 31766078 PMCID: PMC6938763 DOI: 10.1111/1759-7714.13257] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Revised: 10/31/2019] [Accepted: 11/04/2019] [Indexed: 11/28/2022] Open
Abstract
Background Previous investigations have revealed that miR‐563 is associated with a number of diseases including the ossification of posterior longitudinal ligament, Parkinson's disease or drug resistance to leukemia. Yet, the role of miR‐563 and its molecular mechanism in the initiation and progression of cancers has not been previously explored. In this study, we aimed to provide clues to the function of miR‐563 and its direct target in lung cancer. Methods Online informatics software was applied to predict the target genes of miR‐563. MiR‐563 targeting LIN28B was evaluated through the luciferase reporter gene analysis. The effect of miR‐563 on LIN28B at the level of RNA and protein was detected using RT‐PCR and immunoblotting. The ability of proliferation of human lung cancer A549 was examined by MTT assay. RNA interference targeting LIN28B was examined through immunoblotting. The level of miR‐563 and LIN28B and their correlation were analyzed in 27 cases of lung tumor tissues by real‐time PCR. Results Oncogenic LIN28B was identified as one of the target genes of miR‐563 in lung cancer cells. MiR‐563 dose‐dependently decreased the LIN28B RNA level and subsequently its protein level in the cells. Cell proliferation was suppressed by ectopic miR‐563 expression and was accelerated after endogenous miR‐563 was knocked down by its inhibitor. However, silence in LIN28B reversed promotion of cell proliferation by the inhibition of miR‐563. In lung cancer tissues, miR‐563 was decreased and negative correlation of miR‐563 and LIN28B was shown. Conclusion MiR‐563 plays a tumor suppressive role in lung cancer progression via targeting oncogenic LIN28B.
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Affiliation(s)
- Xuefei Zhang
- Department of Thoracic Surgery, The Second Hospital of Dalian Medical University, Dalian, China
| | - Mo Li
- Department of Thoracic Surgery, The Second Hospital of Dalian Medical University, Dalian, China
| | - Ge Sun
- Department of Thoracic Surgery, The Second Hospital of Dalian Medical University, Dalian, China
| | - Yu Bai
- Department of Thoracic Surgery, The Second Hospital of Dalian Medical University, Dalian, China
| | - Desheng Lv
- Department of Thoracic Surgery, The Second Hospital of Dalian Medical University, Dalian, China
| | - Changhong Liu
- Department of Thoracic Surgery, The Second Hospital of Dalian Medical University, Dalian, China
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9
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Yu W, Sun Z, Yang L, Han Y, Yue L, Deng L, Yao R. lncRNA PTAR promotes NSCLC cell proliferation, migration and invasion by sponging microRNA‑101. Mol Med Rep 2019; 20:4168-4174. [PMID: 31485653 PMCID: PMC6797984 DOI: 10.3892/mmr.2019.10646] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 07/26/2019] [Indexed: 02/06/2023] Open
Abstract
MicroRNA (miR)‑101 copy loss is an early event in the development of human lung cancer, and it occurs in 29% of all lung cancer incidences. In addition, miR‑101 expression in non‑small cell lung cancer (NSCLC) is known to be downregulated. The aim of the present study was to explore the roles and mechanisms of the long non‑coding (lnc)‑RNA pro‑transition associated RNA (PTAR) on NSCLC cell proliferation, migration and invasion in association with miR‑101. Reverse transcription‑quantitative PCR analysis was performed to detect the expression of lncRNA PTAR in 30 paired human NSCLC tissues and the corresponding para‑tumor tissues. PTAR was amplified and cloned into the expression vector pCDNA3.1. Then, PTAR‑overexpression plasmids or small interfering (si)‑RNA‑PTAR was transfected into A549 cells for 48 h, after which cell proliferation and the cell cycle distribution were evaluated. In addition, Transwell chamber and cell scratch‑wound assays were conducted to analyze A549 cell migration and invasion. A luciferase activity assay was evaluated to determine the interaction between PTAR and miR‑101. Furthermore, our results demonstrated that in human NSCLC tissues and cell lines, lncRNA PTAR expression was upregulated compared with normal lung tissues and cell lines, respectively. Additionally, PTAR transfection was observed to promote A549 cell proliferation, migration and invasion; opposing effects were observed with siRNA‑PTAR transfection. The luciferase activity assay revealed that PTAR could act as a sponge to bind miR‑101. Thus, miR‑101 plays a role in NSCLC tumorigenesis and progression. In conclusion, lncRNA PTAR was proposed to promote NSCLC cell growth through sponging and inactivating miR‑101, which may be a possible mechanism underlying miR‑101 copy loss in human NSCLC.
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Affiliation(s)
- Wenjun Yu
- Department of Oncology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Zhenni Sun
- Department of Oncology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Ling Yang
- Department of Oncology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Yafei Han
- Department of Central Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
| | - Lu Yue
- Department of Oncology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Lihua Deng
- Department of Oncology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Ruyong Yao
- Department of Central Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
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Weidle UH, Birzele F, Nopora A. MicroRNAs as Potential Targets for Therapeutic Intervention With Metastasis of Non-small Cell Lung Cancer. Cancer Genomics Proteomics 2019; 16:99-119. [PMID: 30850362 PMCID: PMC6489690 DOI: 10.21873/cgp.20116] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 02/11/2019] [Accepted: 02/12/2019] [Indexed: 02/08/2023] Open
Abstract
The death toll of non-small cell lung cancer (NSCLC) patients is primarily due to metastases, which are poorly amenable to therapeutic intervention. In this review we focus on miRs associated with metastasis of NSCLC as potential new targets for anti-metastatic therapy. We discuss miRs validated as therapeutic targets by in vitro data, identification of target(s) and pathway(s) and in vivo efficacy data in at least one clinically-relevant metastasis-related model. A few of the discussed miRs correlate with the clinical status of NSCLC patients. Using miRs as therapeutic agents has the advantage that targeting a single miR can potentially interfere with several metastatic pathways. Depending on their mode of action, the corresponding miRs can be up- or down-regulated compared to normal matching tissues. Here, we describe therapeutic approaches for reconstitution therapy and miR inhibition, general principles of anti-metastatic therapy as well as current technical pitfalls.
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Affiliation(s)
- Ulrich H Weidle
- Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany
| | - Fabian Birzele
- Roche Innovation Center Basel, F. Hofman La Roche, Basel, Switzerland
| | - Adam Nopora
- Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany
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11
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Lu HM, Yi WW, Ma YS, Wu W, Yu F, Fan HW, Lv ZW, Yang HQ, Chang ZY, Zhang C, Xie WT, Jiang JJ, Song YC, Chai L, Jia CY, Lu GX, Zhong XJ, Hou LK, Wu CY, Shi MX, Liu JB, Fu D. Prognostic implications of decreased microRNA-101-3p expression in patients with non-small cell lung cancer. Oncol Lett 2018; 16:7048-7056. [PMID: 30546438 PMCID: PMC6256371 DOI: 10.3892/ol.2018.9559] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Accepted: 08/21/2018] [Indexed: 12/11/2022] Open
Abstract
To investigate the expression level of microRNA-101-3p (miR-101-3p) and its possible association with progression, prognosis and chemotherapy in patients with non-small cell lung cancer (NSCLC), the Gene Expression Omnibus (GEO) database was used. Quantitative polymerase chain reaction was used to verify the expression in 327 NSCLC and 42 adjacent normal lung tissues, of which 42 viable tissues were paired with nearby normal lung tissues. Based on the Cox regression model, univariate and multivariate analyses were used to address the factors that had effects on overall survival (OS) and disease-free survival (DFS) rate. Data from the GEO database demonstrated that the miR-101-3p expression in NSCLC was downregulated, compared with normal lung cancer. Survival analysis through univariate and multivariate models indicated that the miR-101-3p expression level was a crucial risk factor for OS and DFS in patients with NSCLC. A number of clinical parameters were determined to be associated with miR-101-3p expression, including tumor diameter, lymph node metastasis and tumor-node-metastasis stage. Adjuvant chemotherapy with high expression of miR-101-3p was determined to increase OS and DFS in patients with NSCLC, compared with patients with de novo or low expression of miR-101-3p. The present results demonstrated that miR-101-3p expression levels were associated with NSCLC progression and prognosis, which indicated that miR-101-3p may serve as a biomarker for patients with NSCLC who have received adjuvant chemotherapy.
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Affiliation(s)
- Hai-Min Lu
- Department of Thoracic Surgery, Nantong Tumor Hospital, Nantong, Jiangsu 226631, P.R. China
| | - Wan-Wan Yi
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Yu-Shui Ma
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.,Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, College of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China
| | - Wei Wu
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China
| | - Fei Yu
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Heng-Wei Fan
- Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China
| | - Zhong-Wei Lv
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Hui-Qiong Yang
- Department of Pathology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Zheng-Yan Chang
- Department of Pathology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Chao Zhang
- Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China
| | - Wen-Ting Xie
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Jun-Jian Jiang
- Department of Hand Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Ying-Chun Song
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Li Chai
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Cheng-You Jia
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Gai-Xia Lu
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Xiao-Jun Zhong
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangsu 330006, P.R. China
| | - Li-Kun Hou
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China
| | - Chun-Yan Wu
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China
| | - Min-Xin Shi
- Department of Thoracic Surgery, Nantong Tumor Hospital, Nantong, Jiangsu 226631, P.R. China
| | - Ji-Bin Liu
- Department of Thoracic Surgery, Nantong Tumor Hospital, Nantong, Jiangsu 226631, P.R. China
| | - Da Fu
- Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
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12
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Magalhães M, Alvarez-Lorenzo C, Concheiro A, Figueiras A, Santos AC, Veiga F. RNAi-based therapeutics for lung cancer: biomarkers, microRNAs, and nanocarriers. Expert Opin Drug Deliv 2018; 15:965-982. [PMID: 30232915 DOI: 10.1080/17425247.2018.1517744] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Despite the current advances in the discovery of the lung cancer biomarkers and, consequently, in the diagnosis, this pathology continues to be the primary cause of cancer-related death worldwide. In most cases, the illness is diagnosed in an advanced stage, which limits the current treatment options available and reduces the survival rate. Therefore, RNAi-based therapy arises as a promising option to treat lung cancer. AREAS COVERED This review provides an overview on the exploitation of lung cancer biology to develop RNAi-based therapeutics to be applied in the treatment of lung cancer. Furthermore, the review analyzes the main nanocarriers designed to deliver RNAi molecules and induce antitumoral effects in lung cancer, and provides updated information about current RNAi-based therapeutics for lung cancer in clinical trials. EXPERT OPINION RNAi-based therapy uses nanocarriers to perform a targeted and efficient delivery of therapeutic genes into lung cancer cells, by taking advantage of the known biomarkers in lung cancer. These therapeutic genes are key regulatory molecules of crucial cellular pathways involved in cell proliferation, migration, and apoptosis. Thereby, the characteristics and functionalization of the nanocarrier and the knowledge of lung cancer biology have direct influence in improving the therapeutic effect of this therapy.
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Affiliation(s)
- Mariana Magalhães
- a Department of Pharmaceutical Technology, Faculty of Pharmacy , University of Coimbra , Coimbra , Portugal.,b REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy , University of Coimbra , Coimbra , Portugal
| | - Carmen Alvarez-Lorenzo
- c Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, R+D Pharma Group (GI-1645), Facultad de Farmacia and Health Research Institute of Santiago de Compostela (IDIS) , Universidade de Santiago de Compostela , Santiago de Compostela , Spain
| | - Angel Concheiro
- c Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, R+D Pharma Group (GI-1645), Facultad de Farmacia and Health Research Institute of Santiago de Compostela (IDIS) , Universidade de Santiago de Compostela , Santiago de Compostela , Spain
| | - Ana Figueiras
- a Department of Pharmaceutical Technology, Faculty of Pharmacy , University of Coimbra , Coimbra , Portugal.,b REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy , University of Coimbra , Coimbra , Portugal
| | - Ana Cláudia Santos
- a Department of Pharmaceutical Technology, Faculty of Pharmacy , University of Coimbra , Coimbra , Portugal.,b REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy , University of Coimbra , Coimbra , Portugal
| | - Francisco Veiga
- a Department of Pharmaceutical Technology, Faculty of Pharmacy , University of Coimbra , Coimbra , Portugal.,b REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy , University of Coimbra , Coimbra , Portugal
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13
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Zhang J, He J, Zhang L. The down-regulation of microRNA-137 contributes to the up-regulation of retinoblastoma cell proliferation and invasion by regulating COX-2/PGE2 signaling. Biomed Pharmacother 2018; 106:35-42. [PMID: 29945115 DOI: 10.1016/j.biopha.2018.06.099] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Revised: 06/13/2018] [Accepted: 06/13/2018] [Indexed: 02/07/2023] Open
Abstract
MicroRNA-137 (miR-137) plays an important role in the development and progression of many types of human cancers; however, the role of miR-137 in retinoblastoma (RB) remains unclear. In this study, we aimed to investigate the functional significance and molecular mechanisms of miR-137 in RB. We reported that miR-137 was frequently down-regulated in RB tissues and cell lines. The overexpression of miR-137 inhibited RB cell proliferation and invasion, while the suppression of miR-137 promoted RB cell proliferation and invasion. Bioinformatic analysis predicted that cyclooxygenase-2 (COX-2) was a potential target gene of miR-137, which was validated by a dual-luciferase reporter assay. Moreover, our results showed that miR-137 negatively regulated the expression of COX-2 and the production of prostaglandin E2 (PGE2) in RB cells. The knockdown of COX-2 suppressed the proliferation and invasion of RB cells as well as the production of PGE2. The overexpression of COX-2 significantly reversed the inhibitory effect of miR-137 overexpression on RB cell proliferation and invasion. Taken together, these results suggest that miR-137 suppresses the proliferation and invasion of RB cells by targeting COX-2/PGE2. Our study reveals a tumor suppressive role of miR-137 in the progression of RB and suggests miR-137 as a potentially effective therapeutic target for the treatment of RB.
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Affiliation(s)
- Jian Zhang
- Department of Ophthalmology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China
| | - Jing He
- Department of Obstetrics, The First Affiliated Hospital of Xi'an Medical University, Xi'an, 710077, China.
| | - Le Zhang
- Department of Ophthalmology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China
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14
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MicroRNA-132 suppresses cell proliferation in human breast cancer by directly targeting FOXA1. Acta Pharmacol Sin 2018; 39:124-131. [PMID: 28816236 DOI: 10.1038/aps.2017.89] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 05/19/2017] [Indexed: 02/06/2023]
Abstract
Dysregulation of microRNAs (miRNAs) has been implicated in cancer. Recently, miR-132 has been reported to be downregulated in the tissues of patients with breast cancer. In this study, we investigated the functional role of miR-132 and its direct target FOXA1 in breast cancer cells. In 30 human breast cancer tissues, FOXA1 was significantly overexpressed and negatively correlated with miR-132 expression. A bioinformatics analysis suggested that FOXA1 was a potential target of miR-132. Furthermore, dual luciferase reporter assays revealed that miR-132 dose-dependently inhibited the luciferase activity of the wt 3'UTR of FOXA1 rather than the mut 3'UTR of FOXA1 in human MDA-MB-468 and SK-BR3 breast cancer cells. Moreover, ectopic miR-132 expression significantly inhibited FOXA1 protein expression, whereas miR-132 knockdown promoted FOXA1 expression in the breast cancer cells. Ectopic miR-132 expression also suppressed proliferation of the breast cancer cells, whereas miR-132 knockdown promoted proliferation of the breast cancer cells, which was reversed by knockdown of FOXA1 expression. We conclude that MiR-132 suppresses proliferation of breast cancer cells at least partially though inhibition of FOXA1. These results suggest that miR-132 and FOXA1 may be potential biomarkers or therapeutic targets in breast cancer.
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15
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Castro D, Moreira M, Gouveia AM, Pozza DH, De Mello RA. MicroRNAs in lung cancer. Oncotarget 2017; 8:81679-81685. [PMID: 29113423 PMCID: PMC5655318 DOI: 10.18632/oncotarget.20955] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Accepted: 08/26/2017] [Indexed: 01/03/2023] Open
Abstract
Lung cancer (LC) is a serious public health problem responsible for the majority of cancer deaths and comorbidities in developed countries. Tobacco smoking is considered the main risk factor for LC; however, only a few smokers will be affected by this cancer. Current screening methods are focused on identifying the early stages of this malignancy. Thus, new data concerning the roles of microRNA alterations in inflammation, epithelial-mesenchymal transition and lung disease have increased hope about LC pathogenesis, diagnosis, treatment and prognosis. MicroRNA mechanisms include angiogenesis promotion, cell cycle regulation by modulating cellular proliferation and apoptosis, and migration and invasion inhibition. In this context, this manuscript reviews the current information about many important microRNAs as they relate to the initiation and progression of LC.
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Affiliation(s)
- Diana Castro
- Department of Experimental Biology, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Márcia Moreira
- Department of Experimental Biology, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Alexandra Monteiro Gouveia
- Department of Experimental Biology, Faculty of Medicine, University of Porto, Porto, Portugal.,Institute for Cellular and Molecular Biology (IBMC), Institute for Health Innovation, University of Porto, Porto, Portugal.,Faculty of Nutrition and Food Sciences, University of Porto, Porto, Portugal
| | - Daniel Humberto Pozza
- Department of Experimental Biology, Faculty of Medicine, University of Porto, Porto, Portugal.,Faculty of Nutrition and Food Sciences, University of Porto, Porto, Portugal
| | - Ramon Andrade De Mello
- Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal.,Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal
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16
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Zhang X, He X, Liu Y, Zhang H, Chen H, Guo S, Liang Y. MiR-101-3p inhibits the growth and metastasis of non-small cell lung cancer through blocking PI3K/AKT signal pathway by targeting MALAT-1. Biomed Pharmacother 2017; 93:1065-1073. [DOI: 10.1016/j.biopha.2017.07.005] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2017] [Revised: 06/08/2017] [Accepted: 07/03/2017] [Indexed: 12/22/2022] Open
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17
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MicroRNA-4458 suppresses the proliferation of human lung cancer cells in vitro by directly targeting Lin28B. Acta Pharmacol Sin 2017; 38:1297-1304. [PMID: 28603287 DOI: 10.1038/aps.2017.73] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Accepted: 02/20/2017] [Indexed: 12/15/2022]
Abstract
Previous studies have shown that the expression of microRNA-4458 (miR-4458) is dysregulated in hepatocellular carcinoma and colon cancer. In this study, we investigated the direct target of miR-4458 and its biological functions in human lung cancer cells. By using the database TargetScan, we identified Lin28B, an oncogene, as a direct target gene of miR-4458. In dual-luciferase reporter assay, we found that miR-4458 mimics dose-dependently inhibited the luciferase activity of the wild-type 3'UTR of Lin28B in human lung cancer A549 and NCI-H1299 cell lines without affecting its mutant forms, whereas anti-miR-4458, an inhibitor of miR-4458, dose-dependently promoted the luciferase activity of the wild-type 3'UTR of Lin28B in A549 and NCI-H1299 cell lines without affecting its mutant forms. Overexpression of miR-4458 significantly decreased the protein levels of Lin28B in the cells, and inhibited the cell growth and colony formation. Conversely, knockdown of miR-4458 with anti-miR-4458 significantly increased the protein levels of Lin28B, and promoted the cell proliferation, which could be reverted by knockdown of Lin28B expression. In addition, we detected the expression of Lin28B using RT-PCR in 40 human lung cancer tissues and matched peritumoral tissues, and found that Lin28B was overexpressed in lung cancer tissues and negatively correlated with miR-4458 expression (r=-0.694, P<0.05). We conclude that miR-4458 is a tumor suppressor, and Lin28B is the direct target of miR-4458. These results suggest the modulation of miR-4458/Lin28B expression offers a potential therapeutic strategy for lung cancer.
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18
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Bao J, Xu Y, Wang Q, Zhang J, Li Z, Li D, Li J. miR-101 alleviates chemoresistance of gastric cancer cells by targeting ANXA2. Biomed Pharmacother 2017; 92:1030-1037. [PMID: 28609840 DOI: 10.1016/j.biopha.2017.06.011] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 06/05/2017] [Accepted: 06/05/2017] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Chemoresistance remains a main clinical obstacle in the treatment of gastric cancer (GC). microRNAs have been revealed to participate in the regulation of drug resistance in a variety of cancers. However, little is known about the function and detailed molecular mechanism of miR-101 in GC chemoresistance. METHODS The expressions of miR-101 and Annexin A2 (ANXA2) in GC tissues and cells were detected by qRT-PCR and western blot. The effects of miR-101 overexpression on P-glycoprotein (P-gp) at mRNA and protein levels, cell viability, and apoptosis in drug-resistant GC cells were examined by qRT-PCR, western blot, MTT and flow cytometry analysis, respectively. Luciferase reporter assay, RNA immunoprecipitation (RIP) and qRT-PCR were applied to confirm whether miR-101 could target ANXA2 and regulate its expression. Rescue experiment was performed to verify the mechanism by which miR-101 involved in chemoresistance. RESULTS miR-101 was downregulated in GC tissues and drug-resistant GC cells. A negative correlation between miR-101 and ANXA2 expression was observed in GC tissues. Forced expression of miR-101 significantly reduced P-gp expression at mRNA and protein levels in drug-resistant GC cells. Overexpression of miR-101 enhanced sensitivity to cisplatin (DDP) or vincristine (VCR) via viability inhibition and apoptosis promotion. ANXA2 was identified as a direct target of miR-101 and miR-101 negatively regulated ANXA2 expression. Moreover, ectopic expression of ANXA2 reversed the effect of miR-101 on P-gp expression, cell viability and apoptosis. CONCLUSION miR-101 alleviated chemoresistance of gastric cancer cells by targeting ANXA2. Therefore, targeting miR-101 may be a potential therapeutic approach for drug-resistant GC.
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Affiliation(s)
- Jie Bao
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China
| | - Yun Xu
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China
| | - Qunying Wang
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China
| | - Jinping Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China
| | - Zhenjie Li
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China
| | - Dongying Li
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China
| | - Jiansheng Li
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
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Yang HJ, Jiang JH, Yang YT, Yang XD, Guo Z, Qi YP, Zeng FH, Zhang KL, Chen NZ, Xiang BD, Li LQ. Cyclooxygenase-2 expression is associated with initiation of hepatocellular carcinoma, while prostaglandin receptor-1 expression predicts survival. World J Gastroenterol 2016; 22:8798-8805. [PMID: 27818595 PMCID: PMC5075554 DOI: 10.3748/wjg.v22.i39.8798] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Revised: 08/15/2016] [Accepted: 08/30/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To determine whether cyclooxygenase-2 (COX-2) and prostaglandin E1 receptor (EP1) contribute to disease and whether they help predict prognosis.
METHODS We retrospectively reviewed the records of 116 patients with hepatocellular carcinoma (HCC) who underwent surgery between 2008 and 2011 at our hospital. Expression of COX-2 and EP1 receptor was examined by immunohistochemistry of formalin-fixed, paraffin-embedded tissues using polyclonal antibodies. Possible associations between immunohistochemical scores and survival were determined.
RESULTS Factors associated with poor overall survival (OS) were alpha-fetoprotein > 400 ng/mL, tumor size ≥ 5 cm, and high EP1 receptor expression, but not high COX-2 expression. Disease-free survival was not significantly different between patients with low or high levels of COX-2 or EP1. COX-2 immunoreactivity was significantly higher in well-differentiated HCC tissues (Edmondson grade I-II) than in poorly differentiated tissues (Edmondson grade III-IV) (P = 0.003). EP1 receptor immunoreactivity was significantly higher in poorly differentiated tissue than in well-differentiated tissue (P = 0.001).
CONCLUSION COX-2 expression appears to be linked to early HCC events (initiation), while EP1 receptor expression may participate in tumor progression and predict survival.
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20
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Qiu ZA, He GP. MicroRNA-134 functions as a tumor suppressor gene in gastric cancer. Am J Transl Res 2016; 8:4320-4328. [PMID: 27830015 PMCID: PMC5095324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Accepted: 12/15/2015] [Indexed: 06/06/2023]
Abstract
MiR-134 can function as an oncogene or a tumor suppressor gene depending on cell type. However, the function of miR-134 in gastric cancer remains unclear to date. This study aims to evaluate the function of miR-134 in gastric cancer and investigate its effect on the sensitivity of gastric cancer cells to 5-FU. The expression of miR-134 assayed by real-time PCR was significantly lower in gastric cancer tissues than in noncancerous tissues. Over-expression of miR-134 significantly inhibited the proliferation and growth in vivo, as well as promoted the apoptosis of gastric cancer cells by targeting KRAS. Finally, the up-regulation of miR-134 enhanced the sensitivity of gastric cancer cells to 5-FU. In conclusion, miR-134 suppresses tumor development in gastric cancer by targeting KRAS and enhances cell sensitivity to 5-FU. Our results encourage researchers to use 5-FU in combination with miR-134 to treat gastric cancer.
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Affiliation(s)
- Ze-An Qiu
- Nursing School, Central South UniversityNo. 172 Tongzipo Road, Yuelu District, Changsha 410013, Hunan Province, China
- Guiyang Nursing Vocational CollegeNo. 2 Stone Forest Road, Mountain Lakes District, Guiyang 550023, Guizhou Province, China
| | - Guo-Ping He
- Nursing School, Central South UniversityNo. 172 Tongzipo Road, Yuelu District, Changsha 410013, Hunan Province, China
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Abstract
Bone metastasis is a deadly complication of cancers arising from many different primary tumor locations. Cross talk between cancer and bone cells is a well-established driver of bone metastasis, and recent work reveals microRNA (miRNA) as key players in this communication. Functional significance of miRNA was first demonstrated in cancer cells and has now also been documented in bone cell differentiation and skeletal remodeling. Review of recent literature highlights how different miRNAs can impact each step of the metastatic process by acting in both tumor and the metastatic niche to exert pleiotropic effects. Additionally, whether a miRNA is ultimately pro- or anti-metastatic dependents on the context-varied or even opposite outcomes can be conferred by the same miRNA in different cancer/cell types. In spite of this complexity, emerging research has provided a wealth of knowledge to uncover the exciting potential of miRNA as new diagnostic tools and therapeutic treatments for cancer bone metastasis.
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Affiliation(s)
- Scott R Baier
- Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Yihong Wan
- Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
- Simmons Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
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He H, Tian W, Chen H, Deng Y. MicroRNA-101 sensitizes hepatocellular carcinoma cells to doxorubicin-induced apoptosis via targeting Mcl-1. Mol Med Rep 2015; 13:1923-9. [PMID: 26718267 DOI: 10.3892/mmr.2015.4727] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Accepted: 12/08/2015] [Indexed: 11/06/2022] Open
Abstract
MicroRNAs (miRNAs/miRs) are important regulators of multiple cellular processes, and their dysregulation is a common event in tumorigenesis, including the development of hepatocellular carcinoma (HCC). Studies have shown that certain miRNAs are associated with resistance to chemotherapy or drug sensitization; however, the underlying mechanisms have largely remained elusive. Multiple drug resistance is a major barrier for the treatment of advanced HCC. In the present study, miR-101 was observed to be downregulated in a panel of HCC cell lines, suggesting that it has a tumor suppressor role. Furthermore, transfection of miR-101 significantly enhanced the cytotoxicity of doxorubicin to HepG2 cells. While overexpression of miR-101 did not influence the accumulation of doxorubicin, it promoted the apoptosis-inducing effect of doxorubicin in HepG2 cells. A bioinformatics analysis predicted that miR-101 directly targeted the 3'-untranslated region of myeloid cell leukemia 1 (Mcl-1), which was verified by a luciferase reporter assay. Finally, transfection of HepG2 cells with Mcl-1 expression plasmid inhibited apoptosis caused by doxorubicin plus miR-101 expression. In conclusion, the present study showed that miR-101 is a negative regulator of Mcl-1 in HCC, and the combination of miR-101 expression with doxorubicin may represent a novel approach for the treatment of HCC.
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Affiliation(s)
- Haifei He
- Department of Surgical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
| | - Wei Tian
- Department of Surgical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
| | - Hailong Chen
- Department of Surgical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
| | - Yongchuan Deng
- Department of Surgical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
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