|
1
|
Beňačka R, Szabóová D, Guľašová Z, Hertelyová Z. Non-Coding RNAs in Breast Cancer: Diagnostic and Therapeutic Implications. Int J Mol Sci 2024; 26:127. [PMID: 39795985 PMCID: PMC11719911 DOI: 10.3390/ijms26010127] [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: 11/24/2024] [Revised: 12/18/2024] [Accepted: 12/23/2024] [Indexed: 01/13/2025] Open
Abstract
Breast cancer (BC) is one of the most prevalent forms of cancer globally, and has recently become the leading cause of cancer-related mortality in women. BC is a heterogeneous disease comprising various histopathological and molecular subtypes with differing levels of malignancy, and each patient has an individual prognosis. Etiology and pathogenesis are complex and involve a considerable number of genetic alterations and dozens of alterations in non-coding RNA expression. Non-coding RNAs are part of an abundant family of single-stranded RNA molecules acting as key regulators in DNA replication, mRNA processing and translation, cell differentiation, growth, and overall genomic stability. In the context of breast cancer, non-coding RNAs are involved in cell cycle control and tumor cell migration and invasion, as well as treatment resistance. Alterations in non-coding RNA expression may contribute to the development and progression of breast cancer, making them promising biomarkers and targets for novel therapeutic approaches. Currently, the use of non-coding RNAs has not yet been applied to routine practice; however, their potential has been very well studied. The present review is a literature overview of current knowledge and its objective is to delineate the function of diverse classes of non-coding RNAs in breast cancer, with a particular emphasis on their potential utility as diagnostic and prognostic markers or as therapeutic targets and tools.
Collapse
Affiliation(s)
- Roman Beňačka
- Department of Pathophysiology, Medical Faculty, Pavol Jozef Šafarik University, 04011 Košice, Slovakia;
| | - Daniela Szabóová
- Department of Pathophysiology, Medical Faculty, Pavol Jozef Šafarik University, 04011 Košice, Slovakia;
| | - Zuzana Guľašová
- Center of Clinical and Preclinical Research MEDIPARK, Pavol Jozef Šafarik University, 04011 Košice, Slovakia; (Z.G.); (Z.H.)
| | - Zdenka Hertelyová
- Center of Clinical and Preclinical Research MEDIPARK, Pavol Jozef Šafarik University, 04011 Košice, Slovakia; (Z.G.); (Z.H.)
| |
Collapse
|
|
2
|
Mendonza JJ, Reddy ST, Dutta H, Makani VKK, Uppuluri VM, Jain N, Bhadra MP. Retinoic acid and evernyl-based menadione-triazole hybrid cooperate to induce differentiation of neuroblastoma cells. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2023; 396:2651-2665. [PMID: 37097334 DOI: 10.1007/s00210-023-02489-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 04/05/2023] [Indexed: 04/26/2023]
Abstract
Neuroblastoma arises when immature neural precursor cells do not mature into specialized cells. Although retinoic acid (RA), a pro-differentiation agent, improves the survival of low-grade neuroblastoma, resistance to retinoic acid is found in high-grade neuroblastoma patients. Histone deacetylases (HDAC) inhibitors induce differentiation and arrest the growth of cancer cells; however, HDAC inhibitors are FDA-approved mostly for liquid tumors. Therefore, combining histone deacetylase (HDAC) inhibitors and retinoic acid can be explored as a strategy to trigger the differentiation of neuroblastoma cells and to overcome resistance to retinoic acid. Based on this rationale, in this study, we linked evernyl group and menadione-triazole motifs to synthesize evernyl-based menadione-triazole hybrids and asked if the hybrids cooperate with retinoic acid to trigger the differentiation of neuroblastoma cells. To answer this question, we treated neuroblastoma cells using evernyl-based menadione-triazole hybrids (6a-6i) or RA or both and examined the differentiation of neuroblastoma cells. Among the hybrids, we found that compound 6b inhibits class-I HDAC activity, induces differentiation, and RA co-treatments increase 6b-induced differentiation of neuroblastoma cells. In addition, 6b reduces cell proliferation, induces expression of differentiation-specific microRNAs leading to N-Myc downregulation, and RA co-treatments enhance the 6b-induced effects. We observed that 6b and RA trigger a switch from glycolysis to oxidative phosphorylation, maintain mitochondrial polarization, and increase oxygen consumption rate. We conclude that in evernyl-based menadione-triazole hybrid, 6b cooperates with RA to induce differentiation of neuroblastoma cells. Based on our results, we suggest that combining RA and 6b can be pursued as therapy for neuroblastoma. Schematic representation of RA and 6b in inducing differentiation of neuroblastoma cells.
Collapse
Affiliation(s)
- Jolly Janette Mendonza
- Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, Telangana State, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Srilakshmi Tirupathamma Reddy
- Center for Natural Products and Traditional Knowledge, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, Telangana State, India
| | - Hashnu Dutta
- Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, Telangana State, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Venkata Krishna Kanth Makani
- Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, Telangana State, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Venkata Mallavadhani Uppuluri
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
- Center for Natural Products and Traditional Knowledge, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, Telangana State, India.
| | - Nishant Jain
- Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, Telangana State, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
| | - Manika Pal Bhadra
- Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, Telangana State, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
| |
Collapse
|
|
3
|
Anoushirvani AA, Jafarian Yazdi A, Amirabadi S, Asouri SA, Shafabakhsh R, Sheida A, Hosseini Khabr MS, Jafari A, Tamehri Zadeh SS, Hamblin MR, Kalantari L, Talaei Zavareh SA, Mirzaei H. Role of non-coding RNAs in neuroblastoma. Cancer Gene Ther 2023; 30:1190-1208. [PMID: 37217790 DOI: 10.1038/s41417-023-00623-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 03/25/2023] [Accepted: 05/04/2023] [Indexed: 05/24/2023]
Abstract
Neuroblastoma is known as the most prevalent extracranial malignancy in childhood with a neural crest origin. It has been widely accepted that non-coding RNAs (ncRNAs) play important roles in many types of cancer, including glioma and gastrointestinal cancers. They may regulate the cancer gene network. According to recent sequencing and profiling studies, ncRNAs genes are deregulated in human cancers via deletion, amplification, abnormal epigenetic, or transcriptional regulation. Disturbances in the expression of ncRNAs may act either as oncogenes or as anti-tumor suppressor genes, and can lead to the induction of cancer hallmarks. ncRNAs can be secreted from tumor cells inside exosomes, where they can be transferred to other cells to affect their function. However, these topics still need more study to clarify their exact roles, so the present review addresses different roles and functions of ncRNAs in neuroblastoma.
Collapse
Affiliation(s)
- Ali Arash Anoushirvani
- Department of Internal Medicine, Firoozgar Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | - Sanaz Amirabadi
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Sahar Ahmadi Asouri
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University, Kashan, Iran
| | - Rana Shafabakhsh
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University, Kashan, Iran
| | - Amirhossein Sheida
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Maryam Sadat Hosseini Khabr
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Ameneh Jafari
- ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, P.O. BOX: 15179/64311, Tehran, Iran
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
| | - Leila Kalantari
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
| | | | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University, Kashan, Iran.
| |
Collapse
|
|
4
|
Brazane M, Dimitrova DG, Pigeon J, Paolantoni C, Ye T, Marchand V, Da Silva B, Schaefer E, Angelova MT, Stark Z, Delatycki M, Dudding-Byth T, Gecz J, Plaçais PY, Teysset L, Préat T, Piton A, Hassan BA, Roignant JY, Motorin Y, Carré C. The ribose methylation enzyme FTSJ1 has a conserved role in neuron morphology and learning performance. Life Sci Alliance 2023; 6:e202201877. [PMID: 36720500 PMCID: PMC9889914 DOI: 10.26508/lsa.202201877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 01/08/2023] [Accepted: 01/10/2023] [Indexed: 02/02/2023] Open
Abstract
FTSJ1 is a conserved human 2'-O-methyltransferase (Nm-MTase) that modifies several tRNAs at position 32 and the wobble position 34 in the anticodon loop. Its loss of function has been linked to X-linked intellectual disability (XLID), and more recently to cancers. However, the molecular mechanisms underlying these pathologies are currently unclear. Here, we report a novel FTSJ1 pathogenic variant from an X-linked intellectual disability patient. Using blood cells derived from this patient and other affected individuals carrying FTSJ1 mutations, we performed an unbiased and comprehensive RiboMethSeq analysis to map the ribose methylation on all human tRNAs and identify novel targets. In addition, we performed a transcriptome analysis in these cells and found that several genes previously associated with intellectual disability and cancers were deregulated. We also found changes in the miRNA population that suggest potential cross-regulation of some miRNAs with these key mRNA targets. Finally, we show that differentiation of FTSJ1-depleted human neural progenitor cells into neurons displays long and thin spine neurites compared with control cells. These defects are also observed in Drosophila and are associated with long-term memory deficits. Altogether, our study adds insight into FTSJ1 pathologies in humans and flies by the identification of novel FTSJ1 targets and the defect in neuron morphology.
Collapse
Affiliation(s)
- Mira Brazane
- Transgenerational Epigenetics & Small RNA Biology, Sorbonne Université, Centre National de la Recherche Scientifique, Laboratoire de Biologie du Développement - Institut de Biologie Paris Seine, Paris, France
| | - Dilyana G Dimitrova
- Transgenerational Epigenetics & Small RNA Biology, Sorbonne Université, Centre National de la Recherche Scientifique, Laboratoire de Biologie du Développement - Institut de Biologie Paris Seine, Paris, France
| | - Julien Pigeon
- Paris Brain Institute-Institut du Cerveau (ICM), Sorbonne Université, Inserm, CNRS, Hôpital Pitié-Salpêtrière, Paris, France
| | - Chiara Paolantoni
- Center for Integrative Genomics, Génopode Building, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Tao Ye
- Institute of Genetics and Molecular and Cellular Biology, Strasbourg University, CNRS UMR7104, INSERM U1258, Illkirch, France
| | - Virginie Marchand
- Université de Lorraine, CNRS, INSERM, EpiRNASeq Core Facility, UMS2008/US40 IBSLor,Nancy, France
| | - Bruno Da Silva
- Transgenerational Epigenetics & Small RNA Biology, Sorbonne Université, Centre National de la Recherche Scientifique, Laboratoire de Biologie du Développement - Institut de Biologie Paris Seine, Paris, France
| | - Elise Schaefer
- Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Institut de Génétique Médicale d'Alsace, Strasbourg, France
| | - Margarita T Angelova
- Transgenerational Epigenetics & Small RNA Biology, Sorbonne Université, Centre National de la Recherche Scientifique, Laboratoire de Biologie du Développement - Institut de Biologie Paris Seine, Paris, France
| | - Zornitza Stark
- Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia
| | - Martin Delatycki
- Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia
| | | | - Jozef Gecz
- Adelaide Medical School and Robinson Research Institute, The University of Adelaide; South Australian Health and Medical Research Institute, Adelaide, Australia
| | - Pierre-Yves Plaçais
- Energy & Memory, Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, Paris, France
| | - Laure Teysset
- Transgenerational Epigenetics & Small RNA Biology, Sorbonne Université, Centre National de la Recherche Scientifique, Laboratoire de Biologie du Développement - Institut de Biologie Paris Seine, Paris, France
| | - Thomas Préat
- Energy & Memory, Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, Paris, France
| | - Amélie Piton
- Institute of Genetics and Molecular and Cellular Biology, Strasbourg University, CNRS UMR7104, INSERM U1258, Illkirch, France
| | - Bassem A Hassan
- Paris Brain Institute-Institut du Cerveau (ICM), Sorbonne Université, Inserm, CNRS, Hôpital Pitié-Salpêtrière, Paris, France
| | - Jean-Yves Roignant
- Center for Integrative Genomics, Génopode Building, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
- Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Yuri Motorin
- Université de Lorraine, CNRS, UMR7365 IMoPA, Nancy, France
| | - Clément Carré
- Transgenerational Epigenetics & Small RNA Biology, Sorbonne Université, Centre National de la Recherche Scientifique, Laboratoire de Biologie du Développement - Institut de Biologie Paris Seine, Paris, France
| |
Collapse
|
|
5
|
Prinz C, Fehring L, Frese R. MicroRNAs as Indicators of Malignancy in Pancreatic Ductal Adenocarcinoma (PDAC) and Cystic Pancreatic Lesions. Cells 2022; 11:cells11152374. [PMID: 35954223 PMCID: PMC9368175 DOI: 10.3390/cells11152374] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 07/25/2022] [Accepted: 07/30/2022] [Indexed: 12/04/2022] Open
Abstract
The dysregulation of microRNAs has recently been associated with cancer development and progression in pancreatic ductal adenocarcinoma (PDAC) and cystic pancreatic lesions. In solid pancreatic tumor tissue, the dysregulation of miR-146, miR-196a/b, miR-198, miR-217, miR-409, and miR-490, as well as miR-1290 has been investigated in tumor biopsies of patients with PDAC and was reported to predict cancer presence. However, the value of the predictive biomarkers may further be increased during clinical conditions suggesting cancer development such as hyperinsulinemia or onset of diabetes. In this specific context, the dysregulation of miR-486 and miR-196 in tumors has been observed in the tumor tissue of PDAC patients with newly diagnosed diabetes mellitus. Moreover, miR-1256 is dysregulated in pancreatic cancer, possibly due to the interaction with long non-coding RNA molecules that seem to affect cell-cycle control and diabetes manifestation in PDAC patients, and, thus, these three markers may be of special or “sentinel value”. In blood samples, Next-generation sequencing (NGS) has also identified a set of microRNAs (miR-20a, miR-31-5p, miR-24, miR-25, miR-99a, miR-185, and miR-191) that seem to differentiate patients with pancreatic cancer remarkably from healthy controls, but limited data exist in this context regarding the prediction of cancer presences and outcomes. In contrast to solid pancreatic tumors, in cystic pancreatic cancer lesions, as well as premalignant lesions (such as intraductal papillary neoplasia (IPMN) or mucinous-cystic adenomatous cysts (MCAC)), the dysregulation of a completely different expression panel of miR-31-5p, miR-483-5p, miR-99a-5p, and miR-375 has been found to be of high clinical value in differentiating benign from malignant lesions. Interestingly, signal transduction pathways associated with miR-dysregulation seem to be entirely different in patients with pancreatic cysts when compared to PDAC. Overall, the determination of these different dysregulation “panels” in solid tumors, pancreatic cysts, obtained via fine-needle aspirate biopsies and/or in blood samples at the onset or during the treatment of pancreatic diseases, seems to be a reasonable candidate approach for predicting cancer presence, cancer development, and even therapy responses.
Collapse
|
|
6
|
Geng Q, Li Z, Li X, Wu Y, Chen N. LncRNA NORAD, sponging miR-363-3p, promotes invasion and EMT by upregulating PEAK1 and activating the ERK signaling pathway in NSCLC cells. J Bioenerg Biomembr 2021; 53:321-332. [PMID: 33742335 DOI: 10.1007/s10863-021-09892-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 03/09/2021] [Indexed: 12/30/2022]
Abstract
Lung cancer is one of the most common malignant tumors in the world. Non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers. About 75% of patients are in the middle and advanced stages at the time of discovery, and the 5-year survival rate is very low. The aim of this study was to investigate the role of long non-coding RNA (lncRNA) NORAD in the pathogenesis of NSCLC. We found that lncRNA NORAD was highly expressed in human NSCLC tissues and cell lines. The CCK-8 assay results showed that lncRNA NORAD had no effect on cell proliferation. The Transwell assay and Western blotting results showed that overexpression of lncRNA NORAD promoted the invasion and epithelial-mesenchymal transition (EMT) of NSCLC cells. Then bioinformatics analysis was used to screen for candidate miRNA bound with lncRNA NORAD and the target gene of miRNA in NSCLC. The luciferase reporter gene assay and RNA pull-down assay were used to verify the relationship. We found that miR-363-3p expression was down-regulated, whereas PEAK1 expression was upregulated in NSCLC cells. We performed gain and loss function test of lncRNA NORAD, miR-363-3p and PEAK1, the results showed that while miR-363-3p-mimic inhibited cell invasion and EMT by targeting PEAK1, lncRNA NORAD acted as a sponge of miR-363-3p and promoted cell invasion and EMT by increasing the expression of PEAK1. In addition, p-ERK expression was detected by Western blotting to observe the effects of lncRNA NORAD, miR-363-3p and PEAK1 on activation of the ERK signaling pathway. Taken together, lncRNA NORAD upregulated the expression of PEAK1 through sponging miR-363-3p, and then activated the ERK signaling pathway, thereby promoting the development of NSCLC.
Collapse
Affiliation(s)
- Qianqian Geng
- Department of Nuclear Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Zhubin Li
- Department of Minimally Invasive Intervention, Shaanxi Province Tumor Hospital, Xi'an, 710061, China
| | - Xintao Li
- The Second Department of Internal Medicine, Shaanxi Province Tumor Hospital, Xi'an, 710061, China
| | - Yunhua Wu
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Nanzheng Chen
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
| |
Collapse
|
|
7
|
Yuan H, Liu F, Ma T, Zeng Z, Zhang N. miR-338-3p inhibits cell growth, invasion, and EMT process in neuroblastoma through targeting MMP-2. Open Life Sci 2021; 16:198-209. [PMID: 33817311 PMCID: PMC7968531 DOI: 10.1515/biol-2021-0013] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 10/28/2020] [Accepted: 10/29/2020] [Indexed: 12/13/2022] Open
Abstract
This study aimed to explore the regulatory mechanisms of miR-338-3p and matrix metalloproteinase-2 (MMP-2) in neuroblastoma. Putative target interaction regions of miR-338-3p on MMP-2 were predicted by miRcode and miRbase bioinformatics tools. Relative expression of miRNA-338-3p and MMP-2 in neuroblastoma tissues and GI-LI-N and SK-N-SH cells was determined by reverse transcription polymerase chain reaction experiment. Furthermore, the cell proliferation was determined by Cell Counting Kit-8 assay, the cell apoptosis rate was analyzed by flow cytometry assay, and the cell invasion was evaluated by transwell assay. miR-338-3p expression was downregulated, whereas MMP-2 expression was upregulated in metastasis tissue site compared to that in primary tissue site in total. Furthermore, miR-338-3p overexpression suppressed proliferation, invasion, and epithelial-mesenchymal transition (EMT) of neuroblastoma cells but promoted apoptosis, and the knockdown of MMP-2 triggered similar effects. Furthermore, MMP-2 was directly targeted by miR-338-3p, and overexpression of MMP-2 rescued the inhibitory effects of miR-338-3p on human neuroblastoma cell progression. Collectively, these data demonstrated that miR-338-3p could suppress cell growth, invasion, and EMT pathway and induce apoptosis in neuroblastoma cells by targeting MMP-2. MiR-338-3p sponged MMP-2 to regulate the PI3K/AKT pathway in human neuroblastoma cells.
Collapse
Affiliation(s)
- Haibin Yuan
- Department of Neonatal Surgery, Xuzhou Children's Hospital, No.18 Sudi North Road, Quanshan District, 221001, Xuzhou, China
| | - Fengli Liu
- Department of Neonatal Surgery, Xuzhou Children's Hospital, No.18 Sudi North Road, Quanshan District, 221001, Xuzhou, China
| | - Tongsheng Ma
- Department of Neonatal Surgery, Xuzhou Children's Hospital, No.18 Sudi North Road, Quanshan District, 221001, Xuzhou, China
| | - Zhandong Zeng
- Department of Neonatal Surgery, Xuzhou Children's Hospital, No.18 Sudi North Road, Quanshan District, 221001, Xuzhou, China
| | - Ning Zhang
- Department of Neonatal Surgery, Xuzhou Children's Hospital, No.18 Sudi North Road, Quanshan District, 221001, Xuzhou, China
| |
Collapse
|
|
8
|
Dong X, Li Y, Cao R, Xu H. MicroRNA-363-3p Inhibits the Expression of Renal Fibrosis Markers in TGF-β1-Treated HK-2 Cells by Targeting TGF-β2. Biochem Genet 2021; 59:1033-1048. [PMID: 33630202 DOI: 10.1007/s10528-021-10044-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 01/29/2021] [Indexed: 11/30/2022]
Abstract
This study aimed to explore the role of miR-363-3p in renal fibrosis (RF) in vitro. HK-2 cells were treated with transforming growth factor (TGF)-β1 for 72 h to establish an in vitro model of RF. Subsequently, western blot analysis and reverse transcription-quantitative PCR were used to detect the protein and mRNA expression levels of RF markers in TGF-β1-treated HK-2 cells, respectively. The results showed that the protein and mRNA expression levels of TGF-β2, α-smooth muscle actin (SMA), fibronectin, vimentin, collagen II and N-cadherin were increased, while the protein and mRNA expression levels of E-cadherin were decreased in TGF-β1-treated HK-2 cells. The level of miR-363-3p was significantly decreased in TGF-β1-treated HK-2 cells. TargetScan indicated that TGF-β2 was a direct target gene for miR-363-3p, which was further verified using dual luciferase reporter gene assays. Further analyses revealed that the increased protein and mRNA expression levels of TGF-β2, α-SMA, fibronectin, vimentin, collagen II, N-cadherin, increased phosphorylated-Smad3 protein level, and decreased E-cadherin protein and mRNA expression in TGF-β1-treated HK-2 cells were significantly reversed by miR-363-3p mimics. However, all the effects were suppressed by a TGF-β2-plasmid. The results suggested that miR-363-3p plays a protective role in RF by regulating the TGF-β2/Smad3 signaling pathway.
Collapse
Affiliation(s)
- Xiangnan Dong
- Department of Urinary Medicine, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510632, Guangdong, China
| | - Yang Li
- Department of Nephrology, Qingdao Municipal Hospital, 1 Jiaozhou Road, Shibei, Qingdao, 266000, Shandong, China
| | - Rui Cao
- Department of Blood Purification Center, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510632, Guangdong, China
| | - Honglan Xu
- Department of Nephrology, Qingdao Municipal Hospital, 1 Jiaozhou Road, Shibei, Qingdao, 266000, Shandong, China.
| |
Collapse
|
|
9
|
Dong S, Xue S, Sun Y, Han Z, Sun L, Xu J, Liu J. MicroRNA-363-3p downregulation in papillary thyroid cancer inhibits tumor progression by targeting NOB1. J Investig Med 2021; 69:66-74. [PMID: 33077486 PMCID: PMC7803892 DOI: 10.1136/jim-2020-001562] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/24/2020] [Indexed: 12/29/2022]
Abstract
MicroRNA-363-3 p (miR-363-3 p) has been reported to play a crucial role in tumor development and progression, and function as a tumor suppressor in many types of cancer. In our previous studies, we found that miRNA-363-3 p inhibited papillary thyroid carcinoma (PTC) progression by targeting PIK3CA. Meanwhile, we found that NIN1/RPN12 binding protein 1 (NOB1) was significantly upregulated in thyroid carcinoma tissue and downregulation of NOB1 expression significantly inhibited cell proliferation, migration and invasion in PTC. However, the correlation of NOB1 and miR-363-3 p has not been investigated. Here, we performed bioinformatic analysis to explore miRNA targeting NOB1. We found that NOB1 was a target of miR-363-3 p and miR-363-3 p regulated NOB1 expression at the translational and transcriptional levels by targeting its 3' untranslated region (3'-UTR). Further, we showed that miR-363-3 p inhibited tumor progression by targeting NOB1 in vitro and in vivo. We found that overexpression miR-363-3 p or silencing NOB1 significantly increased G0/G1-phase and decreased S-phase in the human papillary thyroid cells, which led to a significant delay in cell proliferation, indicating miR-363-3 p and NOB1 are crucial for human papillary thyroid cancer tumorigenesis. Collectively, our data unveil that miR-363-3 p negatively regulates NOB1 activity by reducing its stability. This study provides a new therapeutic target for regulation of NOB1 stability to modulate human papillary thyroid cancer progression.
Collapse
Affiliation(s)
- Su Dong
- Anesthesia, First Hospital of Jilin University, Changchun, China
| | - Shuai Xue
- Thyroid Surgery, First Hospital of Jilin University, Changchun, China
| | - Yue Sun
- First Operating Room, First Hospital of Jilin University, Changchun, China
| | - Zhe Han
- Thyroid Surgery, First Hospital of Jilin University, Changchun, China
| | - Lele Sun
- Thyroid Surgery, First Hospital of Jilin University, Changchun, China
| | - Jialu Xu
- Thyroid Surgery, First Hospital of Jilin University, Changchun, China
| | - Jia Liu
- Thyroid Surgery, First Hospital of Jilin University, Changchun, China
| |
Collapse
|
|
10
|
Warnecke-Eberz U, Plum P, Schweinsberg V, Drebber U, Bruns CJ, Müller DT, Hölscher AH, Bollschweiler E. Neoadjuvant chemoradiation changes podoplanin expression in esophageal cancer patients. World J Gastroenterol 2020; 26:3236-3248. [PMID: 32684738 PMCID: PMC7336324 DOI: 10.3748/wjg.v26.i23.3236] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 04/20/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Locally advanced adenocarcinoma of the esophagus (EAC) and squamous cell carcinoma (ESCC) result in a worse prognosis. Neoadjuvant treatment improves survival, however, only for responders. The transmembrane glycoprotein podoplanin is overexpressed in squamous cell carcinomas, miRNA-363 is associated to its regulation in head and neck cancer.
AIM To predict therapy response and prognosis markers, and targets for novel therapies would individualize treatments leading to more favourable outcomes.
METHODS Expression of podoplanin protein has been visualized by immunohistochemistry in surgical specimens of 195 esophageal cancer patients who underwent transthoracic esophagectomy: 90 ESCC and 105 EAC with clinical T2-3, Nx, M0. One hundred and six patients received neoadjuvant chemoradiation. RNA was extracted from paraffin-embedded tissue, and miRNA-363 quantified by real-time TaqMan-real-time-PCR. D2-40 mab staining of > 5% was scored as high podoplanin expression (HPE). We related podoplanin and miRNA-363 expression to histopathologic response after neoadjuvant treatment and clinicopathological characteristics, such as histological tumor type, survival rate or clinical tumor category.
RESULTS We confirmed expression of membrane-bound podoplanin in 90 ESCC patients. 26% showed HPE of > 5%. In addition, absence in EAC patients (only 2% with HPE) was shown. Lower podoplanin expression has been detected in resection-specimen of 58 ESCC patients after neoadjuvant (RTx/CTx) treatment, only 11% with HPE, compared to 50% HPE of 32 non-pretreated primary surgery patients, P = 0.0001. This difference of podoplanin expression was confirmed comparing pre-treatment biopsies with matching post-treatment surgical specimens, P < 0.001. Podoplanin has been identified as a prognostic marker in 32 patients that underwent primary surgery without neoadjuvant treatment. Low (0-5%) podoplanin expression was associated with better prognosis compared to patients with HPE, P = 0.013. Podoplanin expression has been associated with post-transcriptional regulation by miRNA-363. At a cut-off value of miR-363 < 7, lower miR-363 expression correlated with HPE in surgical tissue specimens of primary surgery patients, P = 0.013. Therefore, ESCC patients with miRNA-363 expression < 7 had a worse prognosis than patients expressing miRNA-363 ≥ 7, P = 0.049.
CONCLUSION Analysis of the molecular process that leads to decrease in podoplanin expression during neoadjuvant treatment and its regulation may provide novel markers and targets to improve targeted therapy of ESCC.
Collapse
Affiliation(s)
- Ute Warnecke-Eberz
- Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne 50937, Germany
| | - Patrick Plum
- Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne 50937, Germany
| | - Viola Schweinsberg
- Department of Dermatology, University Hospital of Cologne, Cologne 50937, Germany
| | - Uta Drebber
- Institute of Pathology, University Hospital of Cologne, Cologne 50937, Germany
| | - Christiane J Bruns
- Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne 50937, Germany
| | - Dolores T Müller
- Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne 50937, Germany
| | | | - Elfriede Bollschweiler
- Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne 50937, Germany
| |
Collapse
|
|
11
|
Hou C, Wang X, Du B. lncRNA MCM3AP-AS1 promotes the development of oral squamous cell carcinoma by inhibiting miR-363-5p. Exp Ther Med 2020; 20:978-984. [PMID: 32742341 PMCID: PMC7388416 DOI: 10.3892/etm.2020.8738] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 02/04/2020] [Indexed: 01/12/2023] Open
Abstract
The aim of the present study was to study the mechanism of the long non-coding (lnc)RNA MCM3AP-AS1 in the development of oral squamous cell carcinoma (OSCC). Patients with OSCC (n=36) volunteered to join the study, and their tumor/normal tissues were collected. MCM3AP-AS1 and microRNA (miR)-363-5p expression in tissues and cells was determined by reverse transcription-quantitative (RT-q)PCR. Following transfection, a CCK-8 assay and Transwell experiments were conducted to explore the effects of MCM3AP-AS1 on OSCC cell proliferation, migration and invasion. The interaction between MCM3AP-AS1 and miR-363-5p was detected by luciferase reporter gene assay. RT-qPCR analysis demonstrated significantly higher MCM3AP-AS1 expression in tumor tissues or OSCC cells compared with normal tissues or human oral keratinocytes cells (P<0.05). A high MCM3AP-AS1 level was associated with poor prognosis in OSCC patients (P<0.05 or P<0.01). Compared to the small interfering (si)-negative control (NC) group, OSCC cells of si-MCM3AP-AS1 group exhibited markedly lower optical density (at 450 nm) value and relative migration and invasion (P<0.05). miR-363-5p was directly inhibited by MCM3AP-AS1. OSCC cells of si-MCM3AP-AS1 + inhibitor-NC group exhibited clearly lower relative proliferation, migration and invasion compared with cells of si-NC + inhibitor-NC group and si-MCM3AP-AS1 + miR-363-5p inhibitor group (P<0.05). MCM3AP-AS1 promoted OSCC cells proliferation, migration and invasion by inhibiting miR-363-5p.
Collapse
Affiliation(s)
- Chao Hou
- Department of Stomatology, Zaozhuang Municipal Hospital, Zaozhuang, Shandong 277100, P.R. China
| | - Xu Wang
- Department of Stomatology, Zaozhuang Municipal Hospital, Zaozhuang, Shandong 277100, P.R. China
| | - Bo Du
- Department of Stomatology, Zaozhuang Municipal Hospital, Zaozhuang, Shandong 277100, P.R. China
| |
Collapse
|
|
12
|
Beylerli OA, Gareev IF. Micro-RNP as therapeutic targets for neuroblastomas. INNOVATIVE MEDICINE OF KUBAN 2019. [DOI: 10.35401/2500-0268-2019-16-4-66-71] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Neuroblastoma is one of the most common extracranial solid tumors in children. One of the main causes of death from childhood cancer in children aged one to five years, and it accounts for about 15% of all deaths from cancer in children. They have characteristic features, such as an early age of onset, a high frequency of metastasis in the diagnosis of patients older than 1 year and a tendency to spontaneous regression of tumors in young children. Although several prognostic factors were identified (age, stage, histology, heredity), identifying non-invasive biomarkers for disease surveillance and monitoring therapy is indeed still a clinical necessity. In this review, we describe the latest miRNA data in neuroblastoma, with an emphasis on those involved in tumor progression, metastasis, and drug resistance. In addition, we will discuss their potential use in the treatment of this tumor.
Collapse
|
|
13
|
Lu W, Ma YY, Shao QQ, Liang J, Qi TT, Huang Y, Wang QJ. ROS/p53/miR‑335‑5p/Sp1 axis modulates the migration and epithelial to mesenchymal transition of JEG‑3 cells. Mol Med Rep 2019; 21:1208-1216. [PMID: 31894323 PMCID: PMC7003020 DOI: 10.3892/mmr.2019.10901] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 11/18/2019] [Indexed: 11/07/2022] Open
Abstract
Differential expression of microRNA (miR)-335-5p, a key tumor suppressor, has been detected in pre-eclampsia (PE) placentas. However, the role of miR-335-5p in the pathogenesis of PE and the factor modulating its aberrant expression remain unknown. The present study used JEG-3 cells in vitro to investigate these mechanisms. The role of miR-335-5p in proliferation, apoptosis and migration of JEG-3 cells was investigated using MTT, Annexin V-FITC/PI, Transwell migration and wound healing assays, respectively. miR-335-5p expression levels were analyzed using reverse transcription-quantitative PCR. The expression levels of E-cadherin, N-cadherin, Snail, specificity protein 1 (Sp1) and p53 were assessed using western blot analysis. Cell viability analysis was performed using the Cell Counting Kit-8 assay. The intracellular reactive oxygen species (ROS) levels were detected using a 2,7-dichlorodihydrofluorescein diacetate assay. The present results suggested that miR-335-5p did not affect the proliferation or apoptotic rate of JEG-3 cells. Overexpression of miR-335-5p significantly inhibited the migration of JEG-3 cells, decreased the expression levels of Sp1, N-cadherin and Snail, and increased E-cadherin expression. Sp1 silencing produced similar results in JEG-3 cells. H2O2 significantly increased the intracellular ROS levels and miR-335-5p expression, whereas N-acetyl-cysteine pretreatment prior to H2O2 treatment reversed the increases in miR-335-5p expression. Knockdown of p53 significantly decreased the expression levels of miR-335-5p in JEG-3 cells and in H2O2-treated cells. The present results suggested that miR-335-5p expression levels in trophoblast cells could be increased by ROS in a p53-dependent manner, leading to the downregulation of Sp1 and subsequent inhibition of epithelial to mesenchymal transition and cell migration. The present results may provide novel evidence on the etiology of PE.
Collapse
Affiliation(s)
- Wei Lu
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Yu-Yan Ma
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Qian-Qian Shao
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| | - Jie Liang
- Central Sterile Supply Department, People's Hospital of Fangzi, Weifang, Shandong 261200, P.R. China
| | - Tong-Tong Qi
- School of Pharmaceutical Science, Shandong University, Jinan, Shandong 250012, P.R. China
| | - Yi Huang
- School of Pharmaceutical Science, Shandong University, Jinan, Shandong 250012, P.R. China
| | - Qing-Jie Wang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
| |
Collapse
|
|
14
|
Nanotechnological based miRNA intervention in the therapeutic management of neuroblastoma. Semin Cancer Biol 2019; 69:100-108. [PMID: 31562954 DOI: 10.1016/j.semcancer.2019.09.017] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Revised: 08/29/2019] [Accepted: 09/24/2019] [Indexed: 01/07/2023]
Abstract
Neuroblastoma (NB) is a widely diagnosed cancer in children, characterized by amplification of the gene encoding the MYCN transcription factor, which is highly predictive of poor clinical outcome and metastatic disease. microRNAs (a class of small non-coding RNAs) are regulated by MYCN transcription factor in neuroblastoma cells. The current research is focussed on identifying differential role of miRNAs and their interactions with signalling proteins, which are intricately linked with cellular processes like apoptosis, proliferation or metastasis. However, the therapeutic success of miRNAs is limited by pharmaco-technical issues which are well counteracted by nanotechnological advancements. The nanoformulated miRNAs unload anti-cancer drugs in a controlled and prespecified manner at target sites, to influence the activity of target protein in amelioration of NB. Recent advances and developments in the field of miRNAs-based systems for clinical management of NBs and the role of nanotechnology to overcome challenges with drug delivery of miRNAs have been reviewed in this paper.
Collapse
|
|
15
|
Zhang P, Yang X, Wang L, Zhang D, Luo Q, Wang B. Overexpressing miR‑335 inhibits DU145 cell proliferation by targeting early growth response 3 in prostate cancer. Int J Oncol 2019; 54:1981-1994. [PMID: 31081063 PMCID: PMC6521937 DOI: 10.3892/ijo.2019.4778] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Accepted: 03/18/2019] [Indexed: 12/25/2022] Open
Abstract
MicroRNA-335 (miR-335) was reported to suppress cell proliferation in prostate cancer (PC), a common malignancy in males. The expression of early growth response 3 (EGR3) was determined to be elevated in human PC tissues; however, the possible effects and underlying mechanism of miR-335 on PC remains unknown. In the present study, miR-335 mimics and miR-335 inhibitors were respectively transfected into DU145 cells. Stable silencing of EGR3 was observed in DU145 cells following transfection with small interfering RNA. We also used Cell Counting Kit-8 and in vitro angiogenesis assays to determine the viability and revascularization potential of DU145 cells. The expression levels of EGR and caspase-3 activity were analyzed by immunohistochemistry and immunocytochemistry, respectively. We predicted the target of miR-335 by bioinformatics analysis and a dual-luciferase reporter gene assay. Western blot and quantitative real-time polymerase chain reaction analyses were performed to determine the protein and mRNA expression of molecules. miR-335 expression was downregulated in PC tissues and cell lines. Overexpression of miR-335 significantly reduced the viability and the formation of regenerative tubes of DU145 cells, and inhibited the expression of inflammatory factors. EGR3 was proposed as a possible target of miR-335, and was negatively regulated by miR-335. Silencing EGR3 suppressed the viability and angiogenesis of DU145 cells, and reduced the activity of caspase-3 and inflammatory factor expression. miR-335 inhibition along with EGR3 silencing EGR3 inhibited the cell proliferation. Furthermore, miR-335 inhibited the formation of a PC solid tumor xenograft in vivo. Thus, miR-335 may exert an antitumor effect on DU145 cells by regulating the expression of EGR3. The findings of the present study may provide insight into a novel therapeutic strategy for the treatment of prostatic carcinoma.
Collapse
Affiliation(s)
- Peng Zhang
- Department of Urinary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, P.R. China
| | - Xiaojie Yang
- Department of Urinary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, P.R. China
| | - Li Wang
- Department of Urinary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, P.R. China
| | - Dong Zhang
- Department of Urinary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, P.R. China
| | - Qidong Luo
- Department of Urinary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, P.R. China
| | - Binxian Wang
- Department of Urinary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, P.R. China
| |
Collapse
|
|
16
|
Li W, Fan X, Zhang M, Huang L, Lv S, Wang L, Wu Y, Dai C, Xu J, Xu P, Fu Z, Jia X, Shi X. Systematic analysis of hsa-miR-363 gene overexpression pattern in endometrial stromal cells. Int J Mol Med 2018; 42:2793-2800. [PMID: 30226573 DOI: 10.3892/ijmm.2018.3840] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 01/18/2018] [Indexed: 11/06/2022] Open
Abstract
Endometriosis is a benign disease, but has invasion and metastasis characteristics similar to malignant tumors. Clinically, it is a difficult problem of gynecological clinical treatment for its high recurrence rate. It has been confirmed that miR-363 was downregulated in endometriosis tissues and miR-363 overexpression inhibited the invasion ability of endometrial stromal cells (ESCs). In order to explore the potential mechanism of miR-363-reduced ESC migration and invasion progression, we sought to demonstrate the targeted mRNA expression levels of miR-363 through microarray, and performed cluster analysis to identify potential functions of these targeted genes in ESCs. The wound migration assay showed that there was an observable trend of cell migration potential decrease after transfection with hsa-miR-363. The qRT-PCR result showed that compared to miR-363 negative control cell group, miR-363 was upregulated 3,264.58-fold after miR-363 lentiviral transfection in miR-363 mimics group. The microarray data showed that compared to ESCs miR-363 negative control cell group, 249 genes were upregulated in ESCs miR-363 mimics cells group, and 139 genes were downregulated. Gene Ontology analysis and the pathway analysis data demonstrated that these target genes are mainly involved in cell migration, cell adhesion and invasion, proliferation, apoptosis, alteration of endometrial cells and some related signaling pathways. Our study explored the gene expression pattern after miR-363 overexpression, which could expand the insights into the miR-363 function and molecular mechanisms in endometriosis.
Collapse
Affiliation(s)
- Wenqu Li
- Department of Gynecology, Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternal and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China
| | - Xuemei Fan
- Department of Gynecology, Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternal and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China
| | - Mi Zhang
- Department of Gynecology, Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternal and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China
| | - Lei Huang
- Department of General Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China
| | - Shanshan Lv
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China
| | - Luyu Wang
- Soochow University, Soochow, Jiangsu 215004, P.R. China
| | - Ying Wu
- Department of Gynecology, Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternal and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China
| | - Chencheng Dai
- Department of Gynecology, Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternal and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China
| | - Juan Xu
- Department of Gynecology, Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternal and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China
| | - Pengfei Xu
- Department of Gynecology, Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternal and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China
| | - Ziyi Fu
- Department of Gynecology, Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternal and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China
| | - Xuemei Jia
- Department of Gynecology, Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternal and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China
| | - Xiaoyan Shi
- Department of Gynecology, Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternal and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China
| |
Collapse
|
|
17
|
The Potential Contribution of microRNAs in Anti-cancer Effects of Aurora Kinase Inhibitor (AZD1152-HQPA). J Mol Neurosci 2018; 65:444-455. [DOI: 10.1007/s12031-018-1118-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Accepted: 07/10/2018] [Indexed: 12/26/2022]
|
|
18
|
Mohamed Z, Hassan MK, Okasha S, Mitamura T, Keshk S, Konno Y, Kato T, El-Khamisy SF, Ohba Y, Watari H. miR-363 confers taxane resistance in ovarian cancer by targeting the Hippo pathway member, LATS2. Oncotarget 2018; 9:30053-30065. [PMID: 30046387 PMCID: PMC6059020 DOI: 10.18632/oncotarget.25698] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 06/04/2018] [Indexed: 12/12/2022] Open
Abstract
Ovarian cancer is the most aggressive female reproductive tract tumours. Taxane (paclitaxel; TX) is widely used for ovarian cancer treatment. However, ovarian cancers often acquire chemoresistance. MicroRNAs (miR) have been reported to mediate many tumours'chemoresistance. We investigated the role of miR-363 in the chemoresistance of the ovarian cancer cell line, KF, and its TX-resistant derivative (KF-TX) cells. QRT-PCR indicated that miR-363 was upregulated in KF-TX cells, and introduction of miR-363 into sensitive ovarian cancer cells confers TX-resistance and significantly inhibited the expression of the Hippo member, LATS2, as indicated by viability, clonogenic assay and expression analysis. Furthermore, we validated the role of LATS2 in TX-response by sh-based silencing, which also confers TX-resistance to the ovarian cancer cells. On the other hand, specific inhibitor against miR-363 restored the response to TX in the resistant cells. In addition, miR-363 was found to bind to the 3'-UTR of LATS2 mRNA, confirming that miR-363 directly targets LATS2 as indicated by dual luciferase assay. RT-PCR-based evaluation of miR-363 in a panel of human ovarian tumours revealed its upregulation in most of the tumour tissues identified as resistant while it was downregulated in most of the tissues identified as sensitive ones. Moreover, higher levels of miR-363 in human ovarian cancer specimens were significantly correlated with TX chemoresistance. Taken together, our study reveals the involvement of miR-363 in chemoresistance by targeting LATS2 in ovarian cancers, raising the possibility that combination therapy with a miR-363 inhibitor and TX may increase TX efficacy and reduce the chance of TX-resistance.
Collapse
Affiliation(s)
- Zeinab Mohamed
- Zoology Department, Faculty of Science, Aswan University, Aswan, Egypt.,Department of Obstetrics and Gynaecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Mohamed Kamel Hassan
- Department of Obstetrics and Gynaecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.,Bitechnology Program, Zoology Department, Faculty of Science, Port Said University, Port Said, Egypt.,Centre for Genomics, HelmyInstitute for Medical Sciences, Zewail City for Science and Technology, Giza, Egypt
| | - Safwat Okasha
- Zoology Department, Faculty of Science, Aswan University, Aswan, Egypt
| | - Takashi Mitamura
- Department of Obstetrics and Gynaecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Sarah Keshk
- Bitechnology Program, Zoology Department, Faculty of Science, Port Said University, Port Said, Egypt.,Centre for Genomics, HelmyInstitute for Medical Sciences, Zewail City for Science and Technology, Giza, Egypt
| | - Yusuke Konno
- Department of Obstetrics and Gynaecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Tatsuya Kato
- Department of Obstetrics and Gynaecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Sherif F El-Khamisy
- Centre for Genomics, HelmyInstitute for Medical Sciences, Zewail City for Science and Technology, Giza, Egypt.,Krebs and Sheffield Institute for Nucleic Acids, University of Sheffield, Sheffield, UK
| | - Yusuke Ohba
- Department of Cell Physiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Hidemichi Watari
- Department of Obstetrics and Gynaecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| |
Collapse
|
|
19
|
Dong J, Geng J, Tan W. MiR-363-3p suppresses tumor growth and metastasis of colorectal cancer via targeting SphK2. Biomed Pharmacother 2018; 105:922-931. [PMID: 30021386 DOI: 10.1016/j.biopha.2018.06.052] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2018] [Revised: 06/09/2018] [Accepted: 06/12/2018] [Indexed: 11/29/2022] Open
Abstract
Aberrant expression of miR-363-3p is seen in a wide array of cancers. The exact function of miR-363-3p in colorectal cancer (CRC), and the underlying mechanisms remain undefined. In the current study, we observed a down-regulation of miR-363-3p in CRC tissues, along with a strong correlation between low miR-363-3p levels and clinico-pathological parameters like tumor stage and lymph node metastasis. Ectopic overexpression of miR-363-3p in HT29 and HCT116 cell lines effectively inhibited cell proliferation and metastasis, and promoted apoptosis. Concurrently, miR-363-3p inhibition facilitated cell proliferation and suppressed apoptosis. Consistent with the in vitro findings, tumor growth and metastasis were also suppressed by the overexpression of miR-363-3p in vivo. Furthermore, miR-363-3p overexpression resulted in a significant decrease in SphK2 mRNA and protein levels, while miR-363-3p inhibition elevated SphK2 levels in CRC cell lines. Overexpression of SphK2 significantly abrogated the effects of miR-363-3p on cell growth, apoptosis, and metastasis. Taken together, our findings establish miR-363-3p as a potential tumor suppressor in CRC with SphK2 as its downstream target.
Collapse
Affiliation(s)
- Jinlang Dong
- Laiyang Central Hospital, Yantai, Shandong, China
| | - Jianshan Geng
- The 2nd People's Hospital of Laiyang, Yantai, Shandong, China
| | - Weiwei Tan
- Laiyang Central Hospital, Yantai, Shandong, China.
| |
Collapse
|
|
20
|
Li SH, Li JP, Chen L, Liu JL. miR-146a induces apoptosis in neuroblastoma cells by targeting BCL11A. Med Hypotheses 2018; 117:21-27. [PMID: 30077189 DOI: 10.1016/j.mehy.2018.05.019] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 05/13/2018] [Accepted: 05/25/2018] [Indexed: 12/27/2022]
Abstract
Aberrant expression of miR-146a has been reported to be involved in the progression and metastasis of various types of human cancers; however, its potential role in human neuroblastoma is still poorly understood. The purpose of our study was to investigate the molecular mechanism and possible role of miR-146a in human neuroblastoma. In this study, targeted genes were predicted by bioinformatic analysis and confirmed by dual-Luciferase reporter assay. The expression level of miR-146a in the human neuroblastoma SK-N-SH cell line was detected by quantitative RT-PCR. We used flow cytometric analysis to determine apoptosis and necrosis of SK-N-SH cells after transfection with miR-146a inhibitor, miR-146a mimic, and negative controls. The expression level of target genes was detected by RT-PCR and Western blotting. We identified BCL11A as a target of miR-146a. Thus, miR-146a targets the 3'UTR of BCL11A and inhibits its mRNA and protein expression. Overexpression of miR-146a can inhibit the growth and promote the apoptosis of human neuroblastoma SK-N-SH cells through inhibiting the expression of BCL11A. Furthermore, we found that upregulation of BCL11A by miR-146a inhibitor can promote SK-N-SH cells growth and protect SK-N-SH cells against apoptosis. Our results showed that miR-146a is a potential tumor suppressor gene in human neuroblastoma via directly targeting BCL11A. These findings suggest that miR-146a might be a new candidate target for treatment of human neuroblastoma.
Collapse
Affiliation(s)
- Sheng-Hua Li
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University in Nanning, China
| | - Jin-Pin Li
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University in Nanning, China
| | - Lan Chen
- Department of Internal Medicine, The Second Affiliated Hospital of Guangxi Medical University in Nanning, China
| | - Jing-Li Liu
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University in Nanning, China.
| |
Collapse
|
|
21
|
Zhao L, Gu C, Ye M, Zhang Z, Li L, Fan W, Meng Y. Integration analysis of microRNA and mRNA paired expression profiling identifies deregulated microRNA-transcription factor-gene regulatory networks in ovarian endometriosis. Reprod Biol Endocrinol 2018; 16:4. [PMID: 29357938 PMCID: PMC5776778 DOI: 10.1186/s12958-017-0319-5] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2017] [Accepted: 12/25/2017] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND The etiology and pathophysiology of endometriosis remain unclear. Accumulating evidence suggests that aberrant microRNA (miRNA) and transcription factor (TF) expression may be involved in the pathogenesis and development of endometriosis. This study therefore aims to survey the key miRNAs, TFs and genes and further understand the mechanism of endometriosis. METHODS Paired expression profiling of miRNA and mRNA in ectopic endometria compared with eutopic endometria were determined by high-throughput sequencing techniques in eight patients with ovarian endometriosis. Binary interactions and circuits among the miRNAs, TFs, and corresponding genes were identified by the Pearson correlation coefficients. miRNA-TF-gene regulatory networks were constructed using bioinformatic methods. Eleven selected miRNAs and TFs were validated by quantitative reverse transcription-polymerase chain reaction in 22 patients. RESULTS Overall, 107 differentially expressed miRNAs and 6112 differentially expressed mRNAs were identified by comparing the sequencing of the ectopic endometrium group and the eutopic endometrium group. The miRNA-TF-gene regulatory network consists of 22 miRNAs, 12 TFs and 430 corresponding genes. Specifically, some key regulators from the miR-449 and miR-34b/c cluster, miR-200 family, miR-106a-363 cluster, miR-182/183, FOX family, GATA family, and E2F family as well as CEBPA, SOX9 and HNF4A were suggested to play vital regulatory roles in the pathogenesis of endometriosis. CONCLUSION Integration analysis of the miRNA and mRNA expression profiles presents a unique insight into the regulatory network of this enigmatic disorder and possibly provides clues regarding replacement therapy for endometriosis.
Collapse
Affiliation(s)
- Luyang Zhao
- Department of Gynecology and Obstetrics, People’s Liberation Army (PLA) Medical School, Chinese PLA General Hospital, Beijing, 100853 China
- Department of Gynecology and Obstetrics, Peking University People’s Hospital, Beijing, China
| | - Chenglei Gu
- Department of Gynecology and Obstetrics, People’s Liberation Army (PLA) Medical School, Chinese PLA General Hospital, Beijing, 100853 China
- Department of Gynecology and Obstetrics, the 309th Hospital of Chinese PLA, Beijing, China
| | - Mingxia Ye
- Department of Gynecology and Obstetrics, People’s Liberation Army (PLA) Medical School, Chinese PLA General Hospital, Beijing, 100853 China
| | - Zhe Zhang
- Department of Gynecology and Obstetrics, People’s Liberation Army (PLA) Medical School, Chinese PLA General Hospital, Beijing, 100853 China
| | - Li’an Li
- Department of Gynecology and Obstetrics, People’s Liberation Army (PLA) Medical School, Chinese PLA General Hospital, Beijing, 100853 China
| | - Wensheng Fan
- Department of Gynecology and Obstetrics, People’s Liberation Army (PLA) Medical School, Chinese PLA General Hospital, Beijing, 100853 China
| | - Yuanguang Meng
- Department of Gynecology and Obstetrics, People’s Liberation Army (PLA) Medical School, Chinese PLA General Hospital, Beijing, 100853 China
| |
Collapse
|
|
22
|
MiR-143 inhibits endometrial cancer cell proliferation and metastasis by targeting MAPK1. Oncotarget 2017; 8:84384-84395. [PMID: 29137432 PMCID: PMC5663604 DOI: 10.18632/oncotarget.21037] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Accepted: 08/04/2017] [Indexed: 12/31/2022] Open
Abstract
Endometrial cancer (EC) is one of the most commonly diagnosed gynecologic malignancies in the world, with the morbidity rate of over 7%. The mechanism of the pathogenesis has not been specifically elucidated to date, which is imperative for EC treatment. The aim of our study was to investigate the target relationship between miR-143 and mitogen-activated protein kinase 1 (MAPK1) and explore the effect of miR-143 on the endometrial cancers (EC) cells through targeting MAPK1. We collected EC tissues and adjacent tissues, and transfected miR-143 mimics and MAPK1 siRNA into EC cells with lipofectamine. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot were used to examine the expression of miR-143 and MAPK1 mRNA and the protein expression of MAPK1. Cell counting kit-8, wound healing assay, flow cytometry and transwell assay were applied to examining the alteration of the proliferation, migration, cell cycle and invasion ability of EC cells. We predicted the targeting gene of miR-143 through bioinformatics analysis. MiR-143 was found under-expressed in EC tissues and cells. Overexpression of miR-143 or knockdown of MAPK1 in human EC cell line HEC-1B inhibited the EC cell proliferation, migration and invasion and induced apoptosis. MAPK1 was verified to be a target gene of miR-143. MiR-143 overexpression could effectively inhibit mRNA and protein expression of MAPK1 in HEC-1B cells. Collectively, miR-143 might inhibit the proliferation, migration and invasion of EC cells, and promote the apoptosis of EC cells by suppressing MAPK1. These findings provided a view for new and potential therapeutic method for the clinical treatment of EC.
Collapse
|
|
23
|
Ying J, Yu X, Ma C, Zhang Y, Dong J. MicroRNA-363-3p is downregulated in hepatocellular carcinoma and inhibits tumorigenesis by directly targeting specificity protein 1. Mol Med Rep 2017; 16:1603-1611. [PMID: 28627662 DOI: 10.3892/mmr.2017.6759] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 03/23/2017] [Indexed: 11/05/2022] Open
Abstract
microRNAs exhibit important regulatory roles in tumorigenesis and tumor development, such as in hepatocellular carcinoma (HCC). The present study aimed to investigate the expression and functional roles of microRNA (miR)‑363‑3p in HCC. miR-363-3p expression levels in a number of HCC tissues and cell lines were measured by reverse transcription-quantitative PCR (RT‑qPCR). The effects of miR‑363‑3p expression on HCC cell proliferation, migration and invasion were exa-mined by MTT assay, Transwell migration and invasion assay, respectively. The effects of miR‑363‑3p on its downstream target gene, specificity protein 1 (SP1), were examined by bioinformatics analysis, luciferase reporter assay, RT‑qPCR and western blotting. An SP1 overexpression vector was subsequently transfected into HCC cells to assess any selective effects on miR‑363‑3p in modulating HCC. The results revealed that miR‑363‑3p expression levels were downregulated in both HCC tissues and cell lines, and this low expression level was correlated with tumor size, tumor‑node‑metastasis stage and venous infiltration in patients with HCC. Upregulation of miR‑363‑3p inhibited cell proliferation, migration and invasion in HCC cell cultures. In HCC cells transfected with an SP1 expression vector the miR‑363‑3p‑induced tumor suppressive roles on cell proliferation, migration and invasion were reversed. In conclusion, results from the present study indicated that miR‑363‑3p is a tumor suppressor in HCC and functions through a mechanism involving SP1, suggesting that miR‑363‑3p may be a potential new therapeutic target for the treatment of HCC.
Collapse
Affiliation(s)
- Jie Ying
- Department of Gastroenterology, People's Hospital of Xuyi, Xuyi, Jiangsu 211700, P.R. China
| | - Xuechun Yu
- Department of Gastroenterology, People's Hospital of Xuyi, Xuyi, Jiangsu 211700, P.R. China
| | - Chaojian Ma
- Department of Gastroenterology, People's Hospital of Xuyi, Xuyi, Jiangsu 211700, P.R. China
| | - Yongqi Zhang
- Department of Gastroenterology, People's Hospital of Xuyi, Xuyi, Jiangsu 211700, P.R. China
| | - Jingwu Dong
- Department of Gastroenterology, People's Hospital of Xuyi, Xuyi, Jiangsu 211700, P.R. China
| |
Collapse
|
|
24
|
Pan F, Xiang H, Yan J, Hong L, Zhang L, Liu Y, Feng X, Cai C. Dendritic Cells from Rheumatoid Arthritis Patient Peripheral Blood Induce Th17 Cell Differentiation via miR-363/Integrin αv/TGF-β Axis. Scand J Immunol 2017; 85:441-449. [PMID: 28376277 DOI: 10.1111/sji.12550] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Revised: 02/22/2017] [Accepted: 03/13/2017] [Indexed: 12/28/2022]
Abstract
Dendritic cells (DCs) are critical regulators of immune responses. This study was to observe the effect of DCs from peripheral blood on the differentiation of Th17 in patients with rheumatoid arthritis (RA). Peripheral blood samples were collected from 30 patients with RA and 20 healthy controls, respectively. Flow cytometry results showed that in contrast to Treg cells, the proportion of Th17 cells in T cells and the Th17/Treg ratio were both increased in patients with RA. The RT-PCR results showed that Foxp3、ROR γt and miR-363 expression in PBMC of patients with RA were reduced, but the ITGAV expression was increased, which was negatively related to miR-363 expression. IL-17, TGF-β and IL-6 levels detected by ELISA were increased in peripheral blood serum of patients with RA. Moreover, we noted that the CD11C+ αν+ /CD11C+ DCs ratio was obvious increased in patients with RA and has positive correlation to the Th17/Treg ratio. In cocultured system, Th17 cell differentiation was significantly inhibited in the presence of ITGF-β suggesting that Th17 cell differentiation was controlled by active TGF-β (aTGF-β). After DCs transfecting with miR-363 mimics and cocultured with T cells, Th17 cell number, IL-17 level and ROR-γt expression were significantly reduced in the presence of latent TGF-β (ITGF-β). In addition, the integrin αv protein expression was both reduced in the presence of aTGF-β or ITGF-β. These data demonstrated that DCs induced Th17 cell differentiation through miR-363/Integrin αv/TGF-β pathway in patients with RA.
Collapse
Affiliation(s)
| | - H Xiang
- The Affiliated Hospotal of Hangzhou Normal University, Hangzhou, China
| | - J Yan
- The Affiliated Hospotal of Hangzhou Normal University, Hangzhou, China
| | - L Hong
- The Affiliated Hospotal of Hangzhou Normal University, Hangzhou, China
| | - L Zhang
- The Affiliated Hospotal of Hangzhou Normal University, Hangzhou, China
| | - Y Liu
- The Affiliated Hospotal of Hangzhou Normal University, Hangzhou, China
| | - X Feng
- The Affiliated Hospotal of Hangzhou Normal University, Hangzhou, China
| | - C Cai
- The Affiliated Hospotal of Hangzhou Normal University, Hangzhou, China
| |
Collapse
|
|
25
|
Gholamin S, Mirzaei H, Razavi S, Hassanian SM, Saadatpour L, Masoudifar A, ShahidSales S, Avan A. GD2‐targeted immunotherapy and potential value of circulating microRNAs in neuroblastoma. J Cell Physiol 2017; 233:866-879. [DOI: 10.1002/jcp.25793] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Accepted: 01/10/2017] [Indexed: 01/02/2023]
Affiliation(s)
- Sharareh Gholamin
- Institute of Stem Cell Biology and Regenerative MedicineStanford UniversityStanfordCalifornia
- Department of Bioengineering at California Institute of TechnologyPasadenaCalifornia
| | - Hamed Mirzaei
- Department of Medical BiotechnologySchool of MedicineMashhad University of Medical SciencesMashhadIran
| | | | - Seyed Mahdi Hassanian
- Department of Medical BiochemistrySchool of Medicine, Mashhad University of Medical SciencesMashhadIran
- Microanatomy Research CenterMashhad University of Medical SciencesMashhadIran
| | - Leila Saadatpour
- Department of NeurologyUniversity of Florida College of MedicineGainesvilleFlorida
| | - Aria Masoudifar
- Department of Molecular BiotechnologyCell Science Research Center, Royan Institute for Biotechnology, ACECRIsfahanIran
| | - Soodabeh ShahidSales
- Cancer Research CenterSchool of Medicine, Mashhad University of Medical SciencesMashhadIran
| | - Amir Avan
- Metabolic Syndrome Research CenterSchool of Medicine, Mashhad University of Medical SciencesMashhadIran
- Molecular Medicine group, Department of Modern Sciences and TechnologiesMashhad University of Medical SciencesMashhadIran
| |
Collapse
|
|
26
|
Ruan H, Liang X, Zhao W, Ma L, Zhao Y. The effects of microRNA-183 promots cell proliferation and invasion by targeting MMP-9 in endometrial cancer. Biomed Pharmacother 2017; 89:812-818. [PMID: 28273643 DOI: 10.1016/j.biopha.2017.02.091] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Revised: 02/23/2017] [Accepted: 02/23/2017] [Indexed: 01/12/2023] Open
Abstract
MiRNAs are known to play important roles in cancer cell development. However, the pattern and biological role of miR-183 in endometrial cancer (EC) have not been completely unexplored. Here, we found that miR-183 was upregulated in endometrial cancer cells. The purpose of the study was to evaluate the function of miR-183 in the endometrial cancer cell line and the mechanisms regulating its direct target protein in these processes. The mRNA and protein expressions were analyzed by quantitative RT-PCR and western blotting, respectively. The experiments about MTT assay, colony formation assay and transwell assay showed that miR-183 can positively regulate cell proliferation, migration and invasion in vitro. Furthermore, the in vivo experiments indicated that knockdown of miR-183 significantly attenuated EC cells growth. Mechanistically, luciferase reporter assay and western blotting assay was conducted to confirm target associations. The data analysis revealed that MMP-9 as a direct target of miR-183 in EC and there was a negatively relationship between miR-183 and MMP-9 expression in EC cells. Taken together, our results demonstrated that miR-183 plays a critical role in EC tumorigenesis and metastasis by suppressing MMP-9 expression, which may be an attractive therapeutic target for the treatment of endometrial cancer.
Collapse
Affiliation(s)
- Hongjie Ruan
- Department of Gynecology, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing 210000, China
| | - Xin Liang
- Department of Clinical Laboratory, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing 210000, China
| | - Wei Zhao
- Department of Clinical Laboratory, Nanjing Maternity and Child Health Care Hospital, Nanjing 210000, China
| | - Li Ma
- Department of Clinical Laboratory, Huai'an Hospital, Xuzhou Medical University, Huai'an 223002, China.
| | - Yibing Zhao
- Department of Gynecology, Jiangsu Cancer Hospital, Nanjing 210000, China.
| |
Collapse
|
|
27
|
Liu J, Li Q, Li R, Ren P, Dong S. MicroRNA-363-3p inhibits papillary thyroid carcinoma progression by targeting PIK3CA. Am J Cancer Res 2017; 7:148-158. [PMID: 28123856 PMCID: PMC5250689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Accepted: 12/26/2016] [Indexed: 06/06/2023] Open
Abstract
MicroRNA-363-3p (miR-363-3p) reportedly plays crucial roles in tumor development and progression in many types of cancers. However, its role in papillary thyroid carcinoma (PTC) remain largely unclear. We therefore investigated the function and underlying mechanism of miR-363-3p in PTC. Here, we found that miR-363-3p was significantly downregulated in human PTC tissue samples and cell lines, and that miR-363-3p levels are negatively correlated with advanced clinical stage and lymph node metastasis. In addition to suppressing tumor growth in vivo, restoration of miR-363-3p in TPC-1 cells significantly inhibits proliferation, migration, and invasion and induced apoptosis in vitro. Mechanistically, miR-363-3p was verified to directly bind to 3'UTR of the phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) mRNA, and reduce its expression at both mRNA and protein levels, which further inhibits phosphatidylinositol 3-kinase/Akt signaling pathway. PIK3CA expression was also found to be increased in human PTC tissues, and were inversely correlated with miR-363-3p. Furthermore, restoration of PIK3CA partially rescued the miR-363-3p-induced inhibition effect on TPC-1 cell proliferation, migration and invasion. Taken together, these findings indicated for the first time that miR-363-3p functions as a tumor suppressor in PTC, and its suppressive effect is mediated by repressing PIK3CA.
Collapse
Affiliation(s)
- Jia Liu
- Department of Thyroid Surgery, The First Hospital of Jilin University71# Xinmin Street, Chaoyang District, Changchun 130021, Jilin, P. R. China
| | - Qun Li
- Department of Thyroid Surgery, The First Hospital of Jilin University71# Xinmin Street, Chaoyang District, Changchun 130021, Jilin, P. R. China
| | - Rui Li
- Department of Thyroid Surgery, The First Hospital of Jilin University71# Xinmin Street, Chaoyang District, Changchun 130021, Jilin, P. R. China
| | - Peiyou Ren
- Department of Thyroid Surgery, The First Hospital of Jilin University71# Xinmin Street, Chaoyang District, Changchun 130021, Jilin, P. R. China
| | - Su Dong
- Department of Anesthesia, The First Hospital of Jilin University71# Xinmin Street, Chaoyang District, Changchun 130021, Jilin, P. R. China
| |
Collapse
|
|
28
|
Luo LJ, Wang DD, Wang J, Yang F, Tang JH. Diverse roles of miR-335 in development and progression of cancers. Tumour Biol 2016; 37:15399–15410. [PMID: 27718128 DOI: 10.1007/s13277-016-5385-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Accepted: 09/09/2016] [Indexed: 12/16/2022] Open
Abstract
MicroRNAs (miRNAs), a series of small noncoding RNAs that regulate gene expression at the post-transcriptional/translational level, are pivotal in cell differentiation, biological development, occurrence, and development of diseases, especially in cancers. Early studies have shown that miRNA-335 (miR-335) is widely dysregulated in human cancers and play critical roles in tumorigenesis and tumor progression. In this review, we aim to summarize the regulation of miR-335 expression mechanisms in cancers. We focus on the target genes regulated by miR-335 and its downstream signaling pathways involved in the biological effects of tumor growth, invasion, and metastasis both in vitro and in vivo, and analyze the relationships between miR-335 expression and the clinical characteristics of tumors as well as its effects on prognosis. The collected evidences support the potential use of miR-335 in prognosis and diagnosis as well as the therapeutic prospects of miR-335 in cancers.
Collapse
Affiliation(s)
- Long-Ji Luo
- Department of General Surgery, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of General Surgery, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Baiziting 42, Nanjing, 210009, China
| | - Dan-Dan Wang
- Department of General Surgery, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Baiziting 42, Nanjing, 210009, China
- Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jing Wang
- Department of General Surgery, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Baiziting 42, Nanjing, 210009, China
- Nanjing Medical University, Nanjing, Jiangsu, China
| | - Fan Yang
- Department of General Surgery, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of General Surgery, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Baiziting 42, Nanjing, 210009, China
| | - Jin-Hai Tang
- Department of General Surgery, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Baiziting 42, Nanjing, 210009, China.
| |
Collapse
|
|
29
|
Galoian K, Patel P. Epigenetic control of cancer by neuropeptides. Biomed Rep 2016; 6:3-7. [PMID: 28123699 DOI: 10.3892/br.2016.804] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 10/26/2016] [Indexed: 12/26/2022] Open
Abstract
Neuropeptides act as neurohormones, neurotransmitters and/or neuromodulators. Neuropeptides maintain physiological homeostasis and are paramount in molecular mechanisms of disease progression and regulation, including in cancer. Neuropeptides, by their definition, originate and are secreted from the neuronal cells, they are able to signal to neighboring cells or are released into the blood flow, if they act as neurohormones. The majority of neuropeptides exert their functions through G protein-coupled receptors, with certain exceptions. Although previous studies indicate that neuropeptides function in supporting proliferation of malignant cells in many types of solid tumor, the antitumorigenic action of the neuropeptides and their receptors, for example, in gastric cancers and chondrosarcoma, were also reported. It is known that epigenetically modified chromatin regulates molecular mechanisms involved in gene expression and malignant progression. The epigenetic modifications are genetically heritable, although they do not cause changes in DNA sequence. DNA methylation, histone modifications and miRNA expression are subject to those modifications. While there is substantial data on epigenetic regulation of neuropeptides, the epigenetic control of cancer by neuropeptides is considered to be uncharted territory. The aim of the current review is to describe the involvement of neuropeptides in the epigenetic machinery of cancer based on data obtained from our laboratory and from other authors.
Collapse
Affiliation(s)
- Karina Galoian
- Department of Orthopedics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
| | - Parthik Patel
- Department of Orthopedics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
| |
Collapse
|
|
30
|
Karatas OF, Suer I, Yuceturk B, Yilmaz M, Oz B, Guven G, Cansiz H, Creighton CJ, Ittmann M, Ozen M. Identification of microRNA profile specific to cancer stem-like cells directly isolated from human larynx cancer specimens. BMC Cancer 2016; 16:853. [PMID: 27816053 PMCID: PMC5097853 DOI: 10.1186/s12885-016-2863-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2016] [Accepted: 10/04/2016] [Indexed: 12/14/2022] Open
Abstract
Background Emerging evidences proposed that microRNAs are associated with regulation of distinct physio-pathological processes including development of normal stem cells and carcinogenesis. In this study we aimed to investigate microRNA profile of cancer stem-like cells (CSLCs) isolated form freshly resected larynx cancer (LCa) tissue samples. Methods CD133 positive (CD133+) stem-like cells were isolated from freshly resected LCa tumor specimens. MicroRNA profile of 12 pair of CD133+ and CD133− cells was determined using microRNA microarray and differential expressions of selvected microRNAs were validated by quantitative real time PCR (qRT-PCR). Results MicroRNA profiling of CD133+ and CD133− LCa samples with microarray revealed that miR-26b, miR-203, miR-200c, and miR-363-3p were significantly downregulated and miR-1825 was upregulated in CD133+ larynx CSLCs. qRT-PCR analysis in a total of 25 CD133+/CD133− sample pairs confirmed the altered expressions of these five microRNAs. Expressions of miR-26b, miR-200c, and miR-203 were significantly correlated with miR-363-3p, miR-203, and miR-363-3p expressions, respectively. Furthermore, in silico analysis revealed that these microRNAs target both cancer and stem-cell associated signaling pathways. Conclusions Our results showed that certain microRNAs in CD133+ cells could be used as cancer stem cell markers. Based on these results, we propose that this panel of microRNAs might carry crucial roles in LCa pathogenesis through regulating stem cell properties of tumor cells. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2863-3) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Omer Faruk Karatas
- Molecular Biology and Genetics Department, Erzurum Technical University, Erzurum, Turkey
| | - Ilknur Suer
- Department of Medical Genetics, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey
| | - Betul Yuceturk
- Department of Medical Genetics, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey.,Advanced Genomics and Bioinformatics Research Center, The Scientific and Technological Research Council of Turkey (TUBITAK), Gebze, Kocaeli, Turkey
| | - Mehmet Yilmaz
- Department of Otorhinolaryngology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey
| | - Buge Oz
- Department of Pathology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey
| | - Gulgun Guven
- Department of Medical Genetics, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey
| | - Harun Cansiz
- Department of Otorhinolaryngology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey
| | - Chad J Creighton
- Department of Medicine and Dan L. Duncan Cancer Center Division of Biostatistics, Baylor College of Medicine, Houston, TX, USA
| | - Michael Ittmann
- Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, 77030, USA.,Michael E. DeBakey VAMC, Houston, TX, 77030, USA
| | - Mustafa Ozen
- Department of Medical Genetics, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey. .,Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, 77030, USA.
| |
Collapse
|
|
31
|
Onco-GPCR signaling and dysregulated expression of microRNAs in human cancer. J Hum Genet 2016; 62:87-96. [PMID: 27734836 DOI: 10.1038/jhg.2016.124] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Revised: 08/27/2016] [Accepted: 09/09/2016] [Indexed: 02/07/2023]
Abstract
The G-protein-coupled receptor (GPCR) family is the largest family of cell-surface receptors involved in signal transduction. Aberrant expression of GPCRs and G proteins are frequently associated with prevalent human diseases, including cancer. In fact, GPCRs represent the therapeutic targets of more than a quarter of the clinical drugs currently on the market. MiRNAs (miRNAs) are also aberrantly expressed in many human cancers, and they have significant roles in the initiation, development and metastasis of human malignancies. Recent studies have revealed that dysregulation of miRNAs and their target genes expression are associated with cancer progression. The emerging information suggests that miRNAs play an important role in the fine tuning of many signaling pathways, including GPCR signaling. We summarize our current knowledge of the individual functions of miRNAs regulated by GPCRs and GPCR signaling-associated molecules, and miRNAs that regulate the expression and activity of GPCRs, their endogenous ligands and their coupled heterotrimeric G proteins in human cancer.
Collapse
|
|
32
|
Peters DT, Fung HKH, Levdikov VM, Irmscher T, Warrander FC, Greive SJ, Kovalevskiy O, Isaacs HV, Coles M, Antson AA. Human Lin28 Forms a High-Affinity 1:1 Complex with the 106~363 Cluster miRNA miR-363. Biochemistry 2016; 55:5021-7. [PMID: 27559824 PMCID: PMC5193468 DOI: 10.1021/acs.biochem.6b00682] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Lin28A is a post-transcriptional regulator of gene expression that interacts with and negatively regulates the biogenesis of let-7 family miRNAs. Recent data suggested that Lin28A also binds the putative tumor suppressor miR-363, a member of the 106~363 cluster of miRNAs. Affinity for this miRNA and the stoichiometry of the protein-RNA complex are unknown. Characterization of human Lin28's interaction with RNA has been complicated by difficulties in producing stable RNA-free protein. We have engineered a maltose binding protein fusion with Lin28, which binds let-7 miRNA with a Kd of 54.1 ± 4.2 nM, in agreement with previous data on a murine homologue. We show that human Lin28A binds miR-363 with a 1:1 stoichiometry and with a similar, if not higher, affinity (Kd = 16.6 ± 1.9 nM). Further analysis suggests that the interaction of the N-terminal cold shock domain of Lin28A with RNA is salt-dependent, supporting a model in which the cold shock domain allows the protein to sample RNA substrates through transient electrostatic interactions.
Collapse
Affiliation(s)
- Daniel T Peters
- York Structural Biology Laboratory, Department of Chemistry, University of York , York YO10 5DD, United Kingdom
| | - Herman K H Fung
- York Structural Biology Laboratory, Department of Chemistry, University of York , York YO10 5DD, United Kingdom.,Department of Biology, University of York , York YO10 5DD, United Kingdom
| | - Vladimir M Levdikov
- York Structural Biology Laboratory, Department of Chemistry, University of York , York YO10 5DD, United Kingdom
| | - Tobias Irmscher
- York Structural Biology Laboratory, Department of Chemistry, University of York , York YO10 5DD, United Kingdom
| | - Fiona C Warrander
- Department of Biology, University of York , York YO10 5DD, United Kingdom
| | - Sandra J Greive
- York Structural Biology Laboratory, Department of Chemistry, University of York , York YO10 5DD, United Kingdom
| | - Oleg Kovalevskiy
- York Structural Biology Laboratory, Department of Chemistry, University of York , York YO10 5DD, United Kingdom
| | - Harry V Isaacs
- Department of Biology, University of York , York YO10 5DD, United Kingdom
| | - Mark Coles
- Department of Biology, University of York , York YO10 5DD, United Kingdom
| | - Alfred A Antson
- York Structural Biology Laboratory, Department of Chemistry, University of York , York YO10 5DD, United Kingdom
| |
Collapse
|
|
33
|
Boloix A, París-Coderch L, Soriano A, Roma J, Gallego S, Sánchez de Toledo J, Segura MF. Novel micro RNA-based therapies for the treatment of neuroblastoma. An Pediatr (Barc) 2016. [DOI: 10.1016/j.anpede.2015.07.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
|
|
34
|
Hu F, Min J, Cao X, Liu L, Ge Z, Hu J, Li X. MiR-363-3p inhibits the epithelial-to-mesenchymal transition and suppresses metastasis in colorectal cancer by targeting Sox4. Biochem Biophys Res Commun 2016; 474:35-42. [PMID: 27084453 DOI: 10.1016/j.bbrc.2016.04.055] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Accepted: 04/12/2016] [Indexed: 12/18/2022]
|
|
35
|
Understanding the CREB1-miRNA feedback loop in human malignancies. Tumour Biol 2016; 37:8487-502. [PMID: 27059735 DOI: 10.1007/s13277-016-5050-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Accepted: 04/01/2016] [Indexed: 02/07/2023] Open
Abstract
cAMP response element binding protein 1 (CREB1, CREB) is a key transcription factor that mediates transcriptional responses to a variety of growth factors and stress signals. CREB1 has been shown to play a critical role in development and progression of tumors. MicroRNAs (miRNAs) are a class of non-coding RNAs. They post-transcriptionally regulate gene expression through pairing with the 3'-UTR of their target mRNAs and thus regulate initiation and progression of various types of human cancers. Recent studies have demonstrated that a number of miRNAs can be transcriptionally regulated by CREB1. Interestingly, CREB1 expression can also be modulated by miRNAs, thus forming a feedback loop. This review outlines the functional roles of CREB1, miRNA, and their interactions in human malignancies. This will help to define a relationship between CREB1 and miRNA in human cancer and develop novel therapeutic strategies.
Collapse
|
|
36
|
Wang Y, Dong X, Hu B, Wang XJ, Wang Q, Wang WL. The effects of Micro-429 on inhibition of cervical cancer cells through targeting ZEB1 and CRKL. Biomed Pharmacother 2016; 80:311-321. [PMID: 27133071 DOI: 10.1016/j.biopha.2016.03.035] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2016] [Revised: 03/24/2016] [Accepted: 03/25/2016] [Indexed: 12/31/2022] Open
Abstract
MicroRNA-429 (miR-429) has been suggested to inhibit epithelial-mesenchymal transition (EMT), mainly due to targeting of ZEB1 and ZEB2, which are repressors of the cell to cell contact protein, E-cadherin. In this study, we indicated that regulation of miR-429 in cervical cancer cells modulates cell migration, elongation, as well as transforming growth factor β (TGF-β)-induced stress fiber formation through regulating the cytoskeleton reorganization which is likely independent of the zinc finger E-box binding homeobox (ZEB)/E-cadherin axis. ZEB1 and Crk-like adapter protein (CRKL), as novel targets of miR-429 and direct regulators of the actin cytoskeleton were identified. Remarkably, expression levels of ZEB1 and CRKL were inversely associated with the level of miR-429 in cervical cancer cell lines. In addition, individual knockdown and over-expression of these targeting genes phenocopied the roles of miR-429 over-expression and inhibition on cell elongation, migration, stress fiber formation, and invasion. Targeting of ZEB1 by miR-429 led to a decreased expression and transcriptional activity of CRB3, regulated by interference with the translocation of the CRB3. This finally led to decreasing of the expression of Crumbs 3 (CRB3), which is needed for the formation of stress fiber and contractility. Therefore, miR-429 affects cervical cancer by modulating some EMT-related processes. And in this study, evidences were provided to support a role for miR-429 as a novel target suppressing invasion and migration of human cervical cancer cells through modulation of its targeting genes ZEB1 and CRKL. Taken together, our data indicate that miR-429 plays a pivotal role in cervical cancer progression, which is a potential therapeutic target for patients.
Collapse
Affiliation(s)
- Yan Wang
- Department of Obstetrics and Gynecology Surgery, The Second Affiliated Hospital of Zhengzhou University, 2 Jingba Rd., Zhengzhou 450014, Henan, People's Republic of China
| | - Xue Dong
- Department of Obstetrics and Gynecology Surgery, The Second Affiliated Hospital of Zhengzhou University, 2 Jingba Rd., Zhengzhou 450014, Henan, People's Republic of China
| | - Bin Hu
- Department of Obstetrics and Gynecology Surgery, The Second Affiliated Hospital of Zhengzhou University, 2 Jingba Rd., Zhengzhou 450014, Henan, People's Republic of China
| | - Xiao-Jing Wang
- Department of Obstetrics and Gynecology Surgery, The Second Affiliated Hospital of Zhengzhou University, 2 Jingba Rd., Zhengzhou 450014, Henan, People's Republic of China
| | - Qian Wang
- Department of Obstetrics and Gynecology Surgery, The Second Affiliated Hospital of Zhengzhou University, 2 Jingba Rd., Zhengzhou 450014, Henan, People's Republic of China
| | - Wu-Liang Wang
- Department of Obstetrics and Gynecology Surgery, The Second Affiliated Hospital of Zhengzhou University, 2 Jingba Rd., Zhengzhou 450014, Henan, People's Republic of China.
| |
Collapse
|
|
37
|
Khuu C, Utheim TP, Sehic A. The Three Paralogous MicroRNA Clusters in Development and Disease, miR-17-92, miR-106a-363, and miR-106b-25. SCIENTIFICA 2016; 2016:1379643. [PMID: 27127675 PMCID: PMC4834410 DOI: 10.1155/2016/1379643] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/29/2015] [Revised: 03/16/2016] [Accepted: 03/17/2016] [Indexed: 05/06/2023]
Abstract
MicroRNAs (miRNAs) form a class of noncoding RNA genes whose products are small single-stranded RNAs that are involved in the regulation of translation and degradation of mRNAs. There is a fine balance between deregulation of normal developmental programs and tumor genesis. An increasing body of evidence suggests that altered expression of miRNAs is entailed in the pathogenesis of human cancers. Studies in mouse and human cells have identified the miR-17-92 cluster as a potential oncogene. The miR-17-92 cluster is often amplified or overexpressed in human cancers and has recently emerged as the prototypical oncogenic polycistron miRNA. The functional analysis of miR-17-92 is intricate by the existence of two paralogues: miR-106a-363 and miR-106b-25. During early evolution of vertebrates, it is likely that the three clusters commenced via a series of duplication and deletion occurrences. As miR-106a-363 and miR-106b-25 contain miRNAs that are very similar, and in some cases identical, to those encoded by miR-17-92, it is feasible that they regulate a similar set of genes and have overlapping functions. Further understanding of these three clusters and their functions will increase our knowledge about cancer progression. The present review discusses the characteristics and functions of these three miRNA clusters.
Collapse
Affiliation(s)
- Cuong Khuu
- Department of Oral Biology, Faculty of Dentistry, University of Oslo, 0372 Oslo, Norway
- *Cuong Khuu:
| | - Tor Paaske Utheim
- Department of Oral Biology, Faculty of Dentistry, University of Oslo, 0372 Oslo, Norway
- Department of Medical Biochemistry, Oslo University Hospital, 0407 Oslo, Norway
- Department of Ophthalmology, Drammen Hospital, Vestre Viken Hospital Trust, 3004 Drammen, Norway
- Faculty of Health Sciences, University College of South East Norway, 3614 Kongsberg, Norway
| | - Amer Sehic
- Department of Oral Biology, Faculty of Dentistry, University of Oslo, 0372 Oslo, Norway
| |
Collapse
|
|
38
|
MicroRNA expression profiles in pediatric dysembryoplastic neuroepithelial tumors. Med Oncol 2015; 33:5. [PMID: 26698155 DOI: 10.1007/s12032-015-0719-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 12/12/2015] [Indexed: 12/30/2022]
|
|
39
|
Li X, Liu X, Fang J, Li H, Chen J. microRNA-363 plays a tumor suppressive role in osteosarcoma by directly targeting MAP2K4. Int J Clin Exp Med 2015; 8:20157-20167. [PMID: 26884928 PMCID: PMC4723773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Accepted: 11/06/2015] [Indexed: 06/05/2023]
Abstract
Abnormal expression of microRNAs plays important functions in osteosarcoma. The aim of this study was to investigate expression, functions and molecular mechanisms of microRNA-363 in osteosarcoma. Quantitative Real-time PCR was used to detect the expression level of microRNA-363 in osteosarcoma tissue samples and cell lines. After transfection, CCK8 assay, cell migration and invasion assay, western blot and Dual-Luciferase report assay were performed in human osteosarcoma cells. According to the results, we found that microRNA-363 was down-regulated in osteosarcoma tissues and cell lines. In addition, low expression level of microRNA-363 was associated with tumor size, clinical stage and distant metastasis. Moreover, microRNA-363 targeted MAP2K4 to inhibit osteosarcoma cell growth, migration and invasion. In conclusion, microRNA-363 played a tumor suppressive role in osteosarcoma by directly targeting MAP2K4. These findings indicated that microRNA-363 may have therapeutic value in treating osteosarcoma.
Collapse
Affiliation(s)
- Xueqin Li
- Department of Orthopaedic Surgery, Yidu Central Hospital of Weifang, Weifang Medical University Qingzhou 262500, Shandong, China
| | - Xinsheng Liu
- Department of Orthopaedic Surgery, Yidu Central Hospital of Weifang, Weifang Medical University Qingzhou 262500, Shandong, China
| | - Jun Fang
- Department of Orthopaedic Surgery, Yidu Central Hospital of Weifang, Weifang Medical University Qingzhou 262500, Shandong, China
| | - Huazhuang Li
- Department of Orthopaedic Surgery, Yidu Central Hospital of Weifang, Weifang Medical University Qingzhou 262500, Shandong, China
| | - Jingchun Chen
- Department of Orthopaedic Surgery, Yidu Central Hospital of Weifang, Weifang Medical University Qingzhou 262500, Shandong, China
| |
Collapse
|
|
40
|
Chapman BV, Wald AI, Akhtar P, Munko AC, Xu J, Gibson SP, Grandis JR, Ferris RL, Khan SA. MicroRNA-363 targets myosin 1B to reduce cellular migration in head and neck cancer. BMC Cancer 2015; 15:861. [PMID: 26545583 PMCID: PMC4635687 DOI: 10.1186/s12885-015-1888-3] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Accepted: 10/30/2015] [Indexed: 01/07/2023] Open
Abstract
Background Squamous cell carcinoma of the head and neck (SCCHN) remains a prevalent and devastating disease. Recently, there has been an increase in SCCHN cases that are associated with high-risk human papillomavirus (HPV) infection. The clinical characteristics of HPV-positive and HPV-negative SCCHN are known to be different but their molecular features are only recently beginning to emerge. MicroRNAs (miRNAs, miRs) are small, non-coding RNAs that are likely to play significant roles in cancer initiation and progression where they may act as oncogenes or tumor suppressors. Previous studies in our laboratory showed that miR-363 is overexpressed in HPV-positive compared to HPV-negative SCCHN cell lines, and the HPV type 16-E6 oncoprotein upregulates miR-363 in SCCHN cell lines. However, the functional role of miR-363 in SCCHN in the context of HPV infection remains to be elucidated. Methods We analyzed miR-363 levels in SCCHN tumors with known HPV-status from The Cancer Genome Atlas (TCGA) and an independent cohort from our institution. Cell migration studies were conducted following the overexpression of miR-363 in HPV-negative cell lines. Bioinformatic tools and a luciferase reporter assay were utilized to confirm that miR-363 targets the 3’-UTR of myosin 1B (MYO1B). MYO1B mRNA and protein expression levels were evaluated following miR-363 overexpression in HPV-negative SCCHN cell lines. Small interfering RNA (siRNA) knockdown of MYO1B was performed to assess the phenotypic implication of reduced MYO1B expression in SCCHN cell lines. Results MiR-363 was found to be overexpressed in HPV-16-positive compared to the HPV-negative SCCHN tumors. Luciferase reporter assays performed in HPV-negative JHU028 cells confirmed that miR-363 targets one of its two potential binding sites in the 3’UTR of MYO1B. MYO1B mRNA and protein levels were reduced upon miR-363 overexpression in four HPV-negative SCCHN cell lines. Increased miR-363 expression or siRNA knockdown of MYO1B expression reduced Transwell migration of SCCHN cell lines, indicating that the miR-363-induced migration attenuation of SCCHN cells may act through MYO1B downregulation. Conclusions These findings demonstrate that the overexpression of miR-363 reduces cellular migration in head and neck cancer and reveal the biological relationship between miR-363, myosin 1b, and HPV-positive SCCHN. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1888-3) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Bhavana V Chapman
- Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA. .,Department of Otolaryngology, University of Pittsburgh and University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA. .,Medical Research Fellows Program, Howard Hughes Medical Institute, Chevy Chase, MD, 20815, USA.
| | - Abigail I Wald
- Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA.
| | - Parvez Akhtar
- Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA.
| | - Ana C Munko
- Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA.
| | - Jingjing Xu
- Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA.
| | - Sandra P Gibson
- Department of Immunology, University of Pittsburgh, Pittsburgh, PA, 15216, USA. .,Department of Otolaryngology, University of Pittsburgh and University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA.
| | - Jennifer R Grandis
- Department of Otolaryngology, University of Pittsburgh and University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA. .,Department of Pharmacology and Chemical Biology, University of Pittsburgh and University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA. .,Present address: Clinical and Translational Science Institute,, Box 0558, 550 16th Street, 6th Floor, San Francisco, CA, 94158, USA.
| | - Robert L Ferris
- Department of Immunology, University of Pittsburgh, Pittsburgh, PA, 15216, USA. .,Department of Otolaryngology, University of Pittsburgh and University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA.
| | - Saleem A Khan
- Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA.
| |
Collapse
|
|
41
|
Boloix A, París-Coderch L, Soriano A, Roma J, Gallego S, Sánchez de Toledo J, Segura MF. [Novel micro RNA-based therapies for the treatment of neuroblastoma]. An Pediatr (Barc) 2015; 85:109.e1-109.e6. [PMID: 26323526 DOI: 10.1016/j.anpedi.2015.07.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Accepted: 07/12/2015] [Indexed: 12/31/2022] Open
Abstract
Neuroblastoma (NB) is the most common solid tumour in children and adolescents, and accounts for up to 15% of all cancer deaths in this group. It originates in the sympathetic nervous system, and its behaviour can be very aggressive and become resistant to current treatments. A review is presented, summarising the new alternative therapies based on epigenetics, i.e., modulators of gene expression, such as microRNAs and their potential application in the clinical practice of NB treatment.
Collapse
Affiliation(s)
- Ariadna Boloix
- Grupo de Investigación Traslacional en el Cáncer de la infancia y adolescencia, Institut de Recerca, Vall d'Hebron, Barcelona, España
| | - Laia París-Coderch
- Grupo de Investigación Traslacional en el Cáncer de la infancia y adolescencia, Institut de Recerca, Vall d'Hebron, Barcelona, España
| | - Aroa Soriano
- Grupo de Investigación Traslacional en el Cáncer de la infancia y adolescencia, Institut de Recerca, Vall d'Hebron, Barcelona, España
| | - Josep Roma
- Grupo de Investigación Traslacional en el Cáncer de la infancia y adolescencia, Institut de Recerca, Vall d'Hebron, Barcelona, España
| | - Soledad Gallego
- Grupo de Investigación Traslacional en el Cáncer de la infancia y adolescencia, Institut de Recerca, Vall d'Hebron, Barcelona, España; Servicio de Oncología y Hematología Pediátricas, Hospital Universitario Vall d'Hebron, Barcelona, España
| | - Josep Sánchez de Toledo
- Grupo de Investigación Traslacional en el Cáncer de la infancia y adolescencia, Institut de Recerca, Vall d'Hebron, Barcelona, España; Servicio de Oncología y Hematología Pediátricas, Hospital Universitario Vall d'Hebron, Barcelona, España
| | - Miguel F Segura
- Grupo de Investigación Traslacional en el Cáncer de la infancia y adolescencia, Institut de Recerca, Vall d'Hebron, Barcelona, España.
| |
Collapse
|
|
42
|
Chemoresistance, cancer stem cells, and miRNA influences: the case for neuroblastoma. Anal Cell Pathol (Amst) 2015; 2015:150634. [PMID: 26258008 PMCID: PMC4516851 DOI: 10.1155/2015/150634] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 06/26/2015] [Accepted: 07/01/2015] [Indexed: 12/12/2022] Open
Abstract
Neuroblastoma is a type of cancer that develops most often in infants and children under the age of five years. Neuroblastoma originates within the peripheral sympathetic ganglia, with 30% of the cases developing within the adrenal medulla, although it can also occur within other regions of the body such as nerve tissue in the spinal cord, neck, chest, abdomen, and pelvis. MicroRNAs (miRNAs) regulate cellular pathways, differentiation, apoptosis, and stem cell maintenance. Such miRNAs regulate genes involved in cellular processes. Consequently, they are implicated in the regulation of a spectrum of signaling pathways within the cell. In essence, the role of miRNAs in the development of cancer is of utmost importance for the understanding of dysfunctional cellular pathways that lead to the conversion of normal cells into cancer cells. This review focuses on highlighting the recent, important implications of miRNAs within the context of neuroblastoma basic research efforts, particularly concerning miRNA influences on cancer stem cell pathology and chemoresistance pathology for this condition, together with development of translational medicine approaches for novel diagnostic tools and therapies for this neuroblastoma.
Collapse
|
|
43
|
Khan FH, Pandian V, Ramraj S, Aravindan S, Herman TS, Aravindan N. Reorganization of metastamiRs in the evolution of metastatic aggressive neuroblastoma cells. BMC Genomics 2015; 16:501. [PMID: 26148557 PMCID: PMC4491873 DOI: 10.1186/s12864-015-1642-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Accepted: 05/19/2015] [Indexed: 12/19/2022] Open
Abstract
Background MetastamiRs have momentous clinical relevance and have been correlated with disease progression in many tumors. In this study, we identified neuroblastoma metastamiRs exploiting unique mouse models of favorable and high-risk metastatic human neuroblastoma. Further, we related their deregulation to the modulation of target proteins and established their association with clinical outcomes. Results Whole genome miRNA microarray analysis identified 74 metastamiRs across the manifold of metastatic tumors. RT-qPCR on select miRNAs validated profile expression. Results from bio-informatics across the ingenuity pathway, miRCancer, and literature data-mining endorsed the expression of these miRNAs in multiple tumor systems and showed their role in metastasis, identifying them as metastamiRs. Immunoblotting and TMA-IHC analyses revealed alterations in the expression/phosphorylation of metastamiRs’ targets, including ADAMTS-1, AKT1/2/3, ASK1, AURKβ, Birc1, Birc2, Bric5, β-CATENIN, CASP8, CD54, CDK4, CREB, CTGF, CXCR4, CYCLIN-D1, EGFR, ELK1, ESR1, CFOS, FOSB, FRA, GRB10, GSK3β, IL1α, JUND, kRAS, KRTAP1, MCP1, MEGF10, MMP2, MMP3, MMP9, MMP10, MTA2, MYB, cMYC, NF2, NOS3, P21, pP38, PTPN3, CLEAVED PARP, PKC, SDF-1β, SEMA3D, SELE, STAT3, TLR3, TNFα, TNFR1, and VEGF in aggressive cells ex vivo and in a manifold of metastatic tumors in vivo. miRNA mimic (hsa-miR-125b, hsa-miR-27b, hsa-miR-93, hsa-miR-20a) and inhibitor (hsa-miR-1224-3p, hsa-miR-1260) approach for select miRNAs revealed the direct influence of the altered metastamiRs in the regulation of identified protein targets. Clinical outcome association analysis with the validated metastamiRs’ targets corresponded strongly with poor overall and relapse-free survival. Conclusions For the first time, these results identified a comprehensive list of neuroblastoma metastamiRs, related their deregulation to altered expression of protein targets, and established their association with poor clinical outcomes. The identified set of distinctive neuroblastoma metastamiRs could serve as potential candidates for diagnostic markers for the switch from favorable to high-risk metastatic disease. Electronic supplementary material The online version of this article (doi:10.1186/s12864-015-1642-x) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Faizan H Khan
- Department of Radiation Oncology, University of Oklahoma Health Sciences Center, 940, Stanton L. Young Boulevard, BMSB 737, Oklahoma City, OK, 73104, USA.
| | - Vijayabaskar Pandian
- Department of Radiation Oncology, University of Oklahoma Health Sciences Center, 940, Stanton L. Young Boulevard, BMSB 737, Oklahoma City, OK, 73104, USA.
| | - Satishkumar Ramraj
- Department of Radiation Oncology, University of Oklahoma Health Sciences Center, 940, Stanton L. Young Boulevard, BMSB 737, Oklahoma City, OK, 73104, USA.
| | - Sheeja Aravindan
- Stephenson Cancer Center, 975 NE 10th Street, BRC 1468, Oklahoma City, OK, 73104, USA.
| | - Terence S Herman
- Department of Radiation Oncology, University of Oklahoma Health Sciences Center, 940, Stanton L. Young Boulevard, BMSB 737, Oklahoma City, OK, 73104, USA. .,Stephenson Cancer Center, 975 NE 10th Street, BRC 1468, Oklahoma City, OK, 73104, USA.
| | - Natarajan Aravindan
- Department of Radiation Oncology, University of Oklahoma Health Sciences Center, 940, Stanton L. Young Boulevard, BMSB 737, Oklahoma City, OK, 73104, USA.
| |
Collapse
|
|
44
|
Wu K, Yang L, Chen J, Zhao H, Wang J, Xu S, Huang Z. miR-362-5p inhibits proliferation and migration of neuroblastoma cells by targeting phosphatidylinositol 3-kinase-C2β. FEBS Lett 2015; 589:1911-9. [PMID: 26073258 DOI: 10.1016/j.febslet.2015.05.056] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2015] [Revised: 05/24/2015] [Accepted: 05/26/2015] [Indexed: 02/03/2023]
Abstract
miR-362-5p is down-regulated in high-risk neuroblastoma and can function as a tumor suppressor. However, its role remains poorly understood. We show that miR-362-5p is down-regulated in metastatic neuroblastoma compared with primary neuroblastoma. Overexpression of miR-362-5p inhibits cell proliferation, migration and invasion of neuroblastoma cells in vitro and suppresses tumor growth of neuroblastoma in vivo. Phosphatidylinositol 3-kinase (PI3K)-C2β is a target of miR-362-5p. Knockdown of PI3K-C2β by siRNA had a similar effect to overexpression of miR-362-5p on SH-SY5Y cells. Overexpression of PI3K-C2β partially reversed tumor-suppressive effects of miR-362-5p. We suggest that miR-362-5p suppresses neuroblastoma cell growth and motility, partially by targeting PI3K-C2β.
Collapse
Affiliation(s)
- Kai Wu
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China.
| | - Liucheng Yang
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China.
| | - Jianfeng Chen
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China
| | - Haijun Zhao
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China.
| | - Jianjun Wang
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China
| | - Shuai Xu
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China.
| | - Zonghai Huang
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China.
| |
Collapse
|
|
45
|
Gulino R, Forte S, Parenti R, Memeo L, Gulisano M. MicroRNA and pediatric tumors: Future perspectives. Acta Histochem 2015; 117:339-54. [PMID: 25765112 DOI: 10.1016/j.acthis.2015.02.007] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2014] [Revised: 02/02/2015] [Accepted: 02/10/2015] [Indexed: 12/20/2022]
Abstract
A better understanding of pediatric tumor biology is needed to allow the development of less toxic and more efficient therapies, as well as to provide novel reliable biomarkers for diagnosis and risk stratification. The emerging role of microRNAs in controlling key pathways implicated in tumorigenesis makes their use in diagnostics a powerful novel tool for the early detection, risk assessment and prognosis, as well as for the development of innovative anticancer therapies. This perspective would be more urgent for the clinical management of pediatric cancer. In this review, we focus on the involvement of microRNAs in the biology of the main childhood tumors, describe their clinical significance and discuss their potential use as novel therapeutic tools and targets.
Collapse
Affiliation(s)
- Rosario Gulino
- IOM Ricerca s.r.l., Via Penninazzo 11, 95029 Viagrande, Italy.
| | - Stefano Forte
- IOM Ricerca s.r.l., Via Penninazzo 11, 95029 Viagrande, Italy
| | - Rosalba Parenti
- Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 64, 95127 Catania, Italy
| | - Lorenzo Memeo
- IOM Ricerca s.r.l., Via Penninazzo 11, 95029 Viagrande, Italy
| | - Massimo Gulisano
- Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 64, 95127 Catania, Italy
| |
Collapse
|
|
46
|
Gao SL, Wang LZ, Liu HY, Liu DL, Xie LM, Zhang ZW. miR-200a inhibits tumor proliferation by targeting AP-2γ in neuroblastoma cells. Asian Pac J Cancer Prev 2015; 15:4671-6. [PMID: 24969902 DOI: 10.7314/apjcp.2014.15.11.4671] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND MicroRNA-200a (miR-200a) has been reported to regulate tumour progression in several tumours but little is known about its role in neuroblastoma. Our aim was to investigate the potential role and mechanism of miR-200a in neuroblastomas. MATERIALS AND METHODS Expression levels of miR-200a in tissues were determined using RT-PCR. The effect of miR-200a and shAP-2γ on cell viability was evaluated using MTS assays, and target protein expression was determined using Western blotting and RT-PCR. Luciferase reporter plasmids were constructed to confirm direct targeting. RESULTS were reported as mean±S.E.M and differences were tested for significance using the 2-tailed Students t-test. RESULTS We determined that miR-200a expression was significantly lower in neuroblastoma tumors than the adjacent non-cancer tissue. Over-expression of miR-200 are reduced cell viability in neuroblastoma cells and inhibited tumor growth in mouse xenografts. We identified AP-2γ as a novel target for miR-200a in neuroblastoma cells. Thus miR-200a targets the 3'UTR of AP-2γ and inhibits its mRNA and protein expression. Furthermore, our result showed that shRNA knockdown of AP-2γ in neuroblastoma cells results in significant inhibit of cell proliferation and tumor growth in vitro, supporting an oncogenic role of AP-2γ in neuroblastoma. CONCLUSIONS Our study revealed that miR-200a is a candidate tumor suppressor in neuroblastoma, through direct targeting of AP-2γ. These findings re-enforce the proposal of AP-2γ as a therapeutic target in neuroblastoma.
Collapse
Affiliation(s)
- Shun-Li Gao
- Department of pediatrics, The First Affiliated Hospital, University of South China, Hengyang, China E-mail :
| | | | | | | | | | | |
Collapse
|
|
47
|
Zhang R, Li Y, Dong X, Peng L, Nie X. MiR-363 sensitizes cisplatin-induced apoptosis targeting in Mcl-1 in breast cancer. Med Oncol 2014; 31:347. [PMID: 25416050 DOI: 10.1007/s12032-014-0347-3] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Accepted: 11/10/2014] [Indexed: 12/12/2022]
Abstract
Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic Bcl-2 family member that is often overexpressed in breast tumors, and has been reported to have an important role in regulating drug resistance in various types of cancer including breast cancer. However, the mechanisms underlying the aberrant expression of Mcl-1 are still unclear. In this study, we used bioinformatics, cellular, and molecular methods to predict and prove that miR-363 directly targeted Mcl-1 3'-UTR (3'-untranslated regions) and caused downregulation of Mcl-1 in breast cancer. Resistance to chemotherapy is a major barrier for the effective treatment for advanced breast cancer, but our study indicated that miR-363 reversed the resistance of the breast cancer cell line MDA-MB-231 to the chemotherapeutic agent cisplatin (CDDP). In addition, transfection of breast cancer cells with Mcl-1 expression plasmid abolished the sensitization effect of miR-363 to cisplatin-inducing cytotoxicity. In summary, our study showed that miR-363 was a negative regulator of Mcl-1 expression, and the combination of miR-363 and cisplatin may be a novel approach in the treatment for breast cancer.
Collapse
Affiliation(s)
- Ruiguang Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China
| | | | | | | | | |
Collapse
|
|
48
|
Ye ZB, Ma G, Zhao YH, Xiao Y, Zhan Y, Jing C, Gao K, Liu ZH, Yu SJ. miR-429 inhibits migration and invasion of breast cancer cells in vitro. Int J Oncol 2014; 46:531-8. [PMID: 25405387 PMCID: PMC4277243 DOI: 10.3892/ijo.2014.2759] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2014] [Accepted: 10/23/2014] [Indexed: 12/25/2022] Open
Abstract
Accumulating evidence indicates that microRNAs (miRNAs) are involved in regulating cancer invasion and metastasis, and an increasing number of research demonstrates that miRNAs can promote or inhibit cell motility depending on genetic background of different cancers and the microenvironment. In the present study, we established an in vivo bone metastasis model of breast cancer by injecting MDA-MB-231 cells into the left ventricle of nude mice, and then screened the differentially expressed miRNAs between parental and bone-metastatic MDA-MB-231 cells using miRNA array. The results revealed that decreased expression of miR-429 was probably involved in negatively regulating bone metastasis of breast cancer cells. On the other hand, overexpression of miR-429 in MDA-MB-231 cells remarkably suppressed invasion in vitro. We identified ZEB1 and CRKL as potential targets of miR-429 by analyzing combined results from in silico search and global expression array of the same RNA samples. Immunoblot assay confirmed that miR-429 reduced their expression at protein level. Taken together, our results offer an opportunity for further understanding of the recondite mechanisms underlying the bone metastasis of breast cancer.
Collapse
Affiliation(s)
- Zhi-Bin Ye
- Department of Orthopedics, Cancer Hospital (Institute), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Gang Ma
- The State Key Laboratory of Molecular Oncology, Cancer Hospital (Institute), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Ya-Hui Zhao
- The State Key Laboratory of Molecular Oncology, Cancer Hospital (Institute), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Yun Xiao
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China
| | - Yun Zhan
- The State Key Laboratory of Molecular Oncology, Cancer Hospital (Institute), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Chao Jing
- The State Key Laboratory of Molecular Oncology, Cancer Hospital (Institute), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Kai Gao
- Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Zhi-Hua Liu
- The State Key Laboratory of Molecular Oncology, Cancer Hospital (Institute), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Sheng-Ji Yu
- Department of Orthopedics, Cancer Hospital (Institute), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| |
Collapse
|
|
49
|
Uppal A, Ferguson MK, Posner MC, Hellman S, Khodarev NN, Weichselbaum RR. Towards a molecular basis of oligometastatic disease: potential role of micro-RNAs. Clin Exp Metastasis 2014; 31:735-48. [PMID: 24968866 PMCID: PMC4138440 DOI: 10.1007/s10585-014-9664-3] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2014] [Accepted: 06/09/2014] [Indexed: 02/06/2023]
Abstract
Oligometastasis is a cancer disease state characterized by a limited number of metastatic tumors involving single or few organs and with biological properties that make them potentially amenable to locoregional antitumor therapy. Current clinical data show that they are potentially curable with surgical resection or/and radiotherapy. Yet, mechanisms of progression from primary tumor to oligometastasis, rather than to polymetastases, is lacking in detail. In the current review we focus on the role of micro-RNAs in the regulation of metastases development and the role they may play in the differentiation of oligometastatic from polymetastatic progression. We also discuss the analyses of metastatic samples from oligo-and polymetastatic patients, which suggest that oligometastasis is a distinct biologic entity regulated in part by micro-RNAs. In addition, a review of the known functions of oligometastatic-specific micro-RNAs suggest that they regulate multiple steps in the metastatic cascade, including epithelial–mesenchymal transition, tumor invasion, intravasation, distant vascular extravasation and proliferation in a distant organ. Understanding the role of micro-RNAs and their target genes in oligometastatic disease may allow for the development of targeted therapies to effectively conrol the spread of metastases.
Collapse
Affiliation(s)
- Abhineet Uppal
- Department of Surgery, The University of Chicago, MC 5029, 5841 S. Maryland Ave, Chicago, IL, 60637, USA,
| | | | | | | | | | | |
Collapse
|
|
50
|
Significance and therapeutic value of miRNAs in embryonal neural tumors. Molecules 2014; 19:5821-62. [PMID: 24806581 PMCID: PMC6271640 DOI: 10.3390/molecules19055821] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Revised: 04/25/2014] [Accepted: 04/28/2014] [Indexed: 02/07/2023] Open
Abstract
Embryonal tumors of the nervous system are the leading cause of childhood cancer-related morbidity and mortality. Medulloblastoma, supratentorial primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumor and neuroblastoma account for more than 20% of childhood malignancies and typify the current neural embryonal tumor model in pediatric oncology. Mechanisms driving the formation of these tumors point towards impaired differentiation of neuronal and neuron-associated cells during the development of the nervous system as an important factor. The importance of microRNAs (miRNAs) for proper embryonic cell function has been confirmed and their aberrant expressions have been linked to tumor development. The role of miRNAs in controlling essential regulators of key pathways implicated in tumor development makes their use in diagnostics a powerful tool to be used for early detection of cancer, risk assessment and prognosis, as well as for the design of innovative therapeutic strategies. In this review we focus on the significance of miRNAs involved in the biology of embryonal neural tumors, delineate their clinical significance and discuss their potential as a novel therapeutic target.
Collapse
|