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Chavaro-Francisco G, Hernández-Zavala A, Bravo-Cidro CE, Rios-Rodriguez S, Muciño-Sánchez M, López-López M, Castro-Martínez XH, Olarte-Carrillo I, Garcia-Laguna A, Barranco-Lampón G, De la Cruz-Rosas A, Martínez-Tovar A, Córdova EJ. Gene Variants in Components of the microRNA Processing Pathway in Chronic Myeloid Leukemia. Genes (Basel) 2024; 15:1054. [PMID: 39202414 PMCID: PMC11353722 DOI: 10.3390/genes15081054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 08/06/2024] [Accepted: 08/08/2024] [Indexed: 09/03/2024] Open
Abstract
Current therapy in chronic myeloid leukemia (CML) has improved patient life expectancy close to that of healthy individuals. However, molecular alterations other than BCR::ABL1 fusion gene in CML are barely known. MicroRNAs are important regulators of gene expression, and variants in some of the components of microRNA biosynthesis pathways have been associated with genetic susceptibility to different types of cancer. Thus, the aim of this study was to evaluate the association of variants located in genes involved in the biogenesis of microRNAs with susceptibility to CML. Fifteen variants in eight genes involved in the biogenesis of miRNAs were genotyped in 296 individuals with CML and 485 healthy participants using TaqMan probes. The association of gene variants with CML and clinical variables was evaluated by a Chi-square test, and odds ratios and 95% confidence intervals were estimated by logistic regression. The variant rs13078 in DICER1 was significantly higher among CML individuals than in healthy participants. In addition, the variants rs7813 and rs2740349 were significantly associated with worse prognosis, according to their Hasford scores, whereas the rs2740349 variant was also associated with a later age at diagnosis. These findings suggest that variants in components of the microRNA biogenesis pathway could be involved in CML genetic risk.
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Affiliation(s)
- Guillermina Chavaro-Francisco
- Section of Research and Postgraduate Studies, Superior School of Medicine, National Institute Polytechique, Mexico City 11340, Mexico; (G.C.-F.); (A.H.-Z.)
- Oncogenomics Consortium Laboratory, Clinic Research Department, National Institute of Genomic Medicine, Mexico City 14610, Mexico; (C.E.B.-C.); (S.R.-R.); (M.M.-S.)
| | - Araceli Hernández-Zavala
- Section of Research and Postgraduate Studies, Superior School of Medicine, National Institute Polytechique, Mexico City 11340, Mexico; (G.C.-F.); (A.H.-Z.)
| | - Camila E. Bravo-Cidro
- Oncogenomics Consortium Laboratory, Clinic Research Department, National Institute of Genomic Medicine, Mexico City 14610, Mexico; (C.E.B.-C.); (S.R.-R.); (M.M.-S.)
- Department of Biological Systems, Metropolitan Autonomous University, Campus Xochimilco, Mexico City 04960, Mexico;
| | - Sandybel Rios-Rodriguez
- Oncogenomics Consortium Laboratory, Clinic Research Department, National Institute of Genomic Medicine, Mexico City 14610, Mexico; (C.E.B.-C.); (S.R.-R.); (M.M.-S.)
- Department of Biological Systems, Metropolitan Autonomous University, Campus Xochimilco, Mexico City 04960, Mexico;
| | - Mabel Muciño-Sánchez
- Oncogenomics Consortium Laboratory, Clinic Research Department, National Institute of Genomic Medicine, Mexico City 14610, Mexico; (C.E.B.-C.); (S.R.-R.); (M.M.-S.)
- School of Biology, Metropolitan Autonomous University, Campus Xochimilco, Mexico City 04960, Mexico
| | - Marisol López-López
- Department of Biological Systems, Metropolitan Autonomous University, Campus Xochimilco, Mexico City 04960, Mexico;
| | - Xóchitl H. Castro-Martínez
- Genomics of Psychiatric and Neurogenerative Diseases Laboratory, National Institute of Genomic Medicine, Mexico City 14610, Mexico;
| | - Irma Olarte-Carrillo
- Molecular Biology Laboratory, Service of Hematology, Hospital General de Mexico, “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico; (I.O.-C.); (A.G.-L.); (G.B.-L.); (A.M.-T.)
| | - Anel Garcia-Laguna
- Molecular Biology Laboratory, Service of Hematology, Hospital General de Mexico, “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico; (I.O.-C.); (A.G.-L.); (G.B.-L.); (A.M.-T.)
| | - Gilberto Barranco-Lampón
- Molecular Biology Laboratory, Service of Hematology, Hospital General de Mexico, “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico; (I.O.-C.); (A.G.-L.); (G.B.-L.); (A.M.-T.)
| | - Adrián De la Cruz-Rosas
- Molecular Biology Laboratory, Service of Hematology, Hospital General de Mexico, “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico; (I.O.-C.); (A.G.-L.); (G.B.-L.); (A.M.-T.)
| | - Adolfo Martínez-Tovar
- Molecular Biology Laboratory, Service of Hematology, Hospital General de Mexico, “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico; (I.O.-C.); (A.G.-L.); (G.B.-L.); (A.M.-T.)
| | - Emilio J. Córdova
- Oncogenomics Consortium Laboratory, Clinic Research Department, National Institute of Genomic Medicine, Mexico City 14610, Mexico; (C.E.B.-C.); (S.R.-R.); (M.M.-S.)
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Gholamhosseinzadeh E, Ghalehnoei H, Kazemi Veisari A, Jafari N, Goli HR. Evaluation of the Rock1 and microRNA-148a expression in biopsies collected from patients with Helicobacter pylori induced gastritis. BMC Gastroenterol 2024; 24:251. [PMID: 39112943 PMCID: PMC11308716 DOI: 10.1186/s12876-024-03347-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 08/01/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND Helicobacter pylori infection is one of the most common chronic bacterial infections, especially in developing countries. MicroRNA-148a is involved in the regulation of various genes, including Rock1, which is altered in gastric cancer. Decreased expression of mir-148a leads to tumor metastasis and increased Rock1 gene expression in gastric cancer. This study aimed to investigate the expression of these genes in biopsies collected from patients with H. pylori induced gastritis. METHODS Informed consent forms were gotten from the studied patients with gastritis who needed endoscopy. Gastric biopsies were taken by a gastroenterologist from patients with inflammation. Rapid urease test, stool antigen detection, and histopathological staining were used to determine the H. pylori infected patients. Real time PCR was used to evaluate the miRNA and Rock1 expression levels. RESULTS The Rock1 expression level in biopsies that were positive for H. pylori was significantly increased compared to our control gastritis group that were H. pylori-negative, but the results were not statistically significant. Moreover, the mir-148a expression level in H. pylori-positive patients with gastritis was increased compared to our control group. However, the results were not statistically significant. We did not find a significant relation between the expression levels of Rock1 and mir-148a in samples with gastritis infected or uninfected by H. pylori. This result may be due to the small sample size. CONCLUSION We suggest that this test should be carried out with more samples, and the comparison should be done between biopsies with inflammation and no inflammation in a patient.
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Affiliation(s)
- Ebrahim Gholamhosseinzadeh
- Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
- Department of Medical Microbiology and Virology, Faculty of Medicine, Mazandaran University of Medical Sciences, Farah Abad blv, Khazar square, Sari, Mazandaran, Iran
| | - Hossein Ghalehnoei
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Arash Kazemi Veisari
- Gut and Liver Research Center, Non-communicable Disease Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Narjes Jafari
- Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Hamid Reza Goli
- Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
- Department of Medical Microbiology and Virology, Faculty of Medicine, Mazandaran University of Medical Sciences, Farah Abad blv, Khazar square, Sari, Mazandaran, Iran.
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Ren X, Wang X, Song H, Zhang C, Yuan J, He J, Li J, Wang Z. Long non-coding RNA LINC01554 overexpression suppresses viability, migration, and invasion of liver cancer cells through regulating miR-148b-3p/EIF4E3. Heliyon 2024; 10:e27319. [PMID: 38501022 PMCID: PMC10945188 DOI: 10.1016/j.heliyon.2024.e27319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 02/27/2024] [Accepted: 02/27/2024] [Indexed: 03/20/2024] Open
Abstract
Background Long non-coding RNAs (lncRNAs) can be severed as competing endogenous RNAs (ceRNAs) to regulate target genes or mRNAs via sponging microRNAs (miRNAs). This study explored the effect of LINC01554 on liver cancer cells through the ceRNA mechanism. Methods Five significantly down-regulated lncRNAs were selected for further verification, and then through bioinformatics, interactive miRNAs and mRNAs of lncRNAs were identified. The relationship between LINC01554, miR-148b-3p and EIF4E3 was detected by the dual luciferase reporter gene assay. Afterwards, HCCLM3 cells were transfected with pCDH-LINC01554, miR-148b-3p inhibitor and miR-148b-3p mimics. Cell viability, apoptosis, migration and invasion were measured by Cell Counting Kit-8, flow cytometer, and Transwell assays. Real-time quantitative PCR (RT-qPCR) and Western blot were used to measure the expressions of related genes and proteins. Results LINC01554 was significantly down-regulated in the liver cancer cell lines, and was expressed in the cytoplasm of HCCLM3 cells. LINC01554 overexpression inhibited proliferation, migration, and invasion of HCCLM3 cells, and promote their apoptosis (P < 0.05). Besides, LINC01554 overexpression also significantly increased the levels of BAX, BCL2/BAX, P53, cleaved-Caspase3, TIMP3, E-cadherin and EIF4E3 (P < 0.05). Through bioinformatics and dual-luciferase reporter gene assay, LINC01554, miR-148b-3p and EIF4E3 were proved to interact with each other. Furthermore, the effects of miR-148b-3p knockdown on HCCLM3 cells were similar with those of LINC01554 overexpression, and miR-148b-3p mimics could reverse the changes of cell viability, apoptosis, migration, and invasion induced by LINC01554 overexpression. Conclusions LINC01554 overexpression could suppress the growth and metastasis of HCCLM3 cells via miR-148b-3p/EIF4E3.
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Affiliation(s)
- Xiaojing Ren
- Radiological & Environment Medicine Dept, China Institute for Radiation Protection, Taiyuan, 030032, China
- Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China
| | - Xiaoxiao Wang
- Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China
| | - Huangqin Song
- Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China
| | - Chao Zhang
- Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China
| | - Junlong Yuan
- Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China
| | - Jiefeng He
- Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China
| | - Jianguo Li
- Radiological & Environment Medicine Dept, China Institute for Radiation Protection, Taiyuan, 030032, China
| | - Zhuangqiang Wang
- Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China
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Bhardwaj A, Liyanage SI, Weaver DF. Cancer and Alzheimer's Inverse Correlation: an Immunogenetic Analysis. Mol Neurobiol 2023; 60:3086-3099. [PMID: 36797545 DOI: 10.1007/s12035-023-03260-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 02/05/2023] [Indexed: 02/18/2023]
Abstract
Numerous studies have demonstrated an inverse link between cancer and Alzheimer's disease (AD), with data suggesting that people with Alzheimer's have a decreased risk of cancer and vice versa. Although other studies have investigated mechanisms to explain this relationship, the connection between these two diseases remains largely unexplained. Processes seen in cancer, such as decreased apoptosis and increased cell proliferation, seem to be reversed in AD. Given the need for effective therapeutic strategies for AD, comparisons with cancer could yield valuable insights into the disease process and perhaps result in new treatments. Here, through a review of existing literature, we compared the expressions of genes involved in cell proliferation and apoptosis to establish a genetic basis for the reciprocal association between AD and cancer. We discuss an array of genes involved in the aforementioned processes, their relevance to both diseases, and how changes in those genes produce varying effects in either disease.
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Affiliation(s)
- Aditya Bhardwaj
- Krembil Discovery Tower, Krembil Brain Institute, Toronto Western Hospital, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 0S8, Canada
| | - S Imindu Liyanage
- Krembil Discovery Tower, Krembil Brain Institute, Toronto Western Hospital, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 0S8, Canada
| | - Donald F Weaver
- Krembil Discovery Tower, Krembil Brain Institute, Toronto Western Hospital, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 0S8, Canada.
- Departments of Medicine and Chemistry, University of Toronto, Toronto, Canada.
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Li X, Li L, Wu J. The members of the miR-148/152 family inhibit cancer stem cell-like properties in gastric cancer via negative regulation of ITGA5. J Transl Med 2023; 21:105. [PMID: 36765401 PMCID: PMC9912648 DOI: 10.1186/s12967-023-03894-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 01/17/2023] [Indexed: 02/12/2023] Open
Abstract
BACKGROUND The role of microRNA (miRNA) in modulating the function of cancer stem cells through diverse signaling pathway has been evidenced. We here identified a role of microRNA (miRNA) family, specifically miR-148/152, in gastric cancer and delineated its functional effects on gastric cancer stem cells. METHODS Bioinformatics analysis was conducted to analyze expression of integrin α5 (ITGA5) which was verified through expression determination in clinical tissue samples. Next, the upstream regulatory factors of ITGA5 were determined. CD44+EpCAM (high) cells sorted from AGS cells subjected to gain-of-function experiments, followed by evaluation of their capacity of colony formation, generation of tumorosphere, cell migration and viability in vitro and xenograft tumor formation in vivo. RESULTS ITGA5 was elevated in gastric cancer tissues and confirmed as a target gene of the miR-148/152 family members. The miR-148/152 family members were downregulated in gastric cancer tissues and cells. Decreased expression of miR-148/152 family members was also detected in gastric cancer stem cells. However, the raised expression led to reduced colony formation, tumorosphere, cell migration, cell viability, and drug resistance of CD44+EpCAM (high) AGS cells in vitro, and tumorigenesis in vitro. ITGA5 overexpression reversed the effect of the miR-148/152 family members. CONCLUSIONS This study demonstrates that the miR-148/152 family members may prevent gastric cancer stem cell-like properties by targeting ITGA5, which can serve as an appealing target for gastric cancer treatment.
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Affiliation(s)
- Xiaoying Li
- grid.412644.10000 0004 5909 0696Department of Oncology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032 People’s Republic of China
| | - Lin Li
- grid.412644.10000 0004 5909 0696Department of Oncology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032 People’s Republic of China
| | - Jiangying Wu
- Department of Intervention, The Fourth Affiliated Hospital of China Medical University, No. 4, Chongshan East Road, Huanggu District, Shenyang, 110032, Liaoning, People's Republic of China.
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Evaluation of circulating small extracellular vesicle-derived miRNAs as diagnostic biomarkers for differentiating between different pathological types of early lung cancer. Sci Rep 2022; 12:17201. [PMID: 36229645 PMCID: PMC9561663 DOI: 10.1038/s41598-022-22194-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 10/11/2022] [Indexed: 01/06/2023] Open
Abstract
Lung cancer is the leading cause of cancer-related death worldwide. MicroRNAs (miRNAs) in circulating small extracellular vesicles (sEVs) have been suggested to be potential biomarkers for cancer diagnosis. The present study was designed to explore whether plasma-derived sEV miRNAs could be utilized as diagnostic biomarkers for differentiating between early-stage small cell lung cancer (SCLC) and early-stage non-small cell lung cancer (NSCLC). We compared the miRNA profiles of plasma-derived sEVs from healthy individuals, patients with early-stage SCLC and patients with early-stage NSCLC. Next-generation sequencing was used to screen for differentially expressed miRNAs (DEMs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict the potential functions of these DEMs. Weighted gene coexpression network analysis (WGCNA) was used to identify the different pathology-related miRNA modules. We found that 22 DEMs were significantly different among healthy individuals, patients with early-stage SCLC, and patients with early-stage NSCLC. We selected six representative DEMs for validation by qRT‒PCR, which confirmed that miRNA-483-3p derived from plasma sEVs could be used as a potential biomarker for the diagnosis of early-stage SCLC, miRNA-152-3p and miRNA-1277-5p could be used for the diagnosis of early-stage NSCLC respectively.
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Kong W, Yin G, Zheng S, Liu X, Zhu A, Yu P, Zhang J, Shan Y, Ying R, Jin H. Long noncoding RNA (lncRNA) HOTAIR: Pathogenic roles and therapeutic opportunities in gastric cancer. Genes Dis 2022; 9:1269-1280. [PMID: 35873034 PMCID: PMC9293693 DOI: 10.1016/j.gendis.2021.07.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 06/21/2021] [Accepted: 07/06/2021] [Indexed: 01/17/2023] Open
Abstract
Gastric cancer is one of the first malignant cancers in the world and a large number of people die every year due to this disease. Many genetic and epigenetic risk factors have been identified that play a major role in gastric cancer. HOTAIR is an effective epigenetic agent known as long noncoding RNA (lncRNA). HOTAIR has been described to have biological functions in biochemical and cellular processes through interactions with many factors, leading to genomic stability, proliferation, survival, invasion, migration, metastasis, and drug resistance. In the present article, we reviewed the prognostic value of the molecular mechanisms underlying the HOTAIR regulation and its function in the development of Gastric Cancer, whereas elucidation of HOTAIR–protein and HOTAIR–DNA interactions can be helpful in the identification of cancer processes, leading to the development of potential therapeutic strategies.
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Affiliation(s)
- Wencheng Kong
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Guang Yin
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Sixin Zheng
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Xinchun Liu
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Akao Zhu
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Panpan Yu
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Jian Zhang
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Yuqiang Shan
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Rongchao Ying
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
| | - Huicheng Jin
- Department of Gastroenterological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China
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Emirzeoglu L, Olmez O, Mustafayev F, Berber U, Yilmaz I, Celik S, Oven B, Ozgun M. Prognostic value of expression levels of miR‑148a, miR‑152 and HLA‑G in colon cancer. Oncol Lett 2022; 24:226. [PMID: 35720471 PMCID: PMC9185158 DOI: 10.3892/ol.2022.13347] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 04/26/2022] [Indexed: 11/05/2022] Open
Affiliation(s)
- Levent Emirzeoglu
- Department of Medical Oncology, University of Health Sciences, Sultan II. Abdulhamid Khan Educational and Research Hospital, 34660 Istanbul, Turkey
| | - Ozgur Olmez
- Department of Medical Oncology, University of Health Sciences, Sultan II. Abdulhamid Khan Educational and Research Hospital, 34660 Istanbul, Turkey
| | - Fatma Mustafayev
- Department of Medical Oncology, University of Health Sciences, Sultan II. Abdulhamid Khan Educational and Research Hospital, 34660 Istanbul, Turkey
| | - Ufuk Berber
- Department of Pathology, University of Health Sciences, Sultan II. Abdulhamid Khan Educational and Research Hospital, 34660 Istanbul, Turkey
| | - Ismail Yilmaz
- Department of Pathology, University of Health Sciences, Sultan II. Abdulhamid Khan Educational and Research Hospital, 34660 Istanbul, Turkey
| | - Serkan Celik
- Department of Medical Oncology, Yeditepe University Koşuyolu Hospital, 34718 Istanbul, Turkey
| | - Bala Oven
- Department of Medical Oncology, Yeditepe University Koşuyolu Hospital, 34718 Istanbul, Turkey
| | - Mehmet Ozgun
- Department of Medical Oncology, University of Health Sciences, Sultan II. Abdulhamid Khan Educational and Research Hospital, 34660 Istanbul, Turkey
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Mirzajani E, Vahidi S, Norollahi SE, Samadani AA. Novel biomarkers of microRNAs in gastric cancer; an overview from diagnosis to treatment. Microrna 2022; 11:12-24. [PMID: 35319404 DOI: 10.2174/2211536611666220322160242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 12/06/2021] [Accepted: 12/28/2021] [Indexed: 11/22/2022]
Abstract
The fourth frequent disease in the world and the second cause of cancer-related death is gastric cancer (GC). In this way, over 80% of diagnoses are made in the middle to advanced degrees of the disease, underscoring the requirement for innovative biomarkers that can be identified quickly. Meaningly, biomarkers that can complement endoscopic diagnosis and be used to detect patients with a high risk of GC are desperately needed. These biomarkers will allow for the accurate prediction of therapy response and prognosis in GC patients, as well as the development of an optimal treatment strategy for each individual. Conspicoiusly, microRNAs (miRNAs) and small noncoding RNA regulates the expression of target mRNA and thereby modifies critical biological mechanisms. According to the data, abnormally miRNAs expression in GC is linked to tumor growth, carcinogenesis, aggression and distant metastasis. Importantly, miRNA expression patterns and next-generation sequencing (NGS) can also be applied to analyze kinds of tissues and cancers. Given the high death rates and poor prognosis of GC, and the absence of a clinical diagnostic factor that is adequately sensitive to GC, research into novel sensitive and specific markers for GC diagnosis is critical. In this review,we evaluate the latest research findings that suggest the feasibility and clinical utility of miRNAs in GC.
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Affiliation(s)
- Ebrahim Mirzajani
- Department of Biochemistry, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
- Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Sogand Vahidi
- Clinical Research Development Unit of Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Seyedeh Elham Norollahi
- Cancer Research Center and Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
| | - Ali Akbar Samadani
- Guilan Road Trauma Research Center, Guilan University of Medical Sciences, Rasht, Iran
- Clinical Research Development Unit of Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran
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Zamberlan M, Boeckx A, Muller F, Vinelli F, Ek O, Vianello C, Coart E, Shibata K, Christian A, Grespi F, Giacomello M, Struman I, Scorrano L, Herkenne S. Inhibition of the mitochondrial protein Opa1 curtails breast cancer growth. J Exp Clin Cancer Res 2022; 41:95. [PMID: 35279198 PMCID: PMC8917763 DOI: 10.1186/s13046-022-02304-6] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 02/26/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Mitochondrial fusion and fission proteins have been nominated as druggable targets in cancer. Whether their inhibition is efficacious in triple negative breast cancer (TNBC) that almost invariably develops chemoresistance is unknown. METHODS We used a combination of bioinformatics analyses of cancer genomic databases, genetic and pharmacological Optic Atrophy 1 (OPA1) inhibition, mitochondrial function and morphology measurements, micro-RNA (miRNA) profiling and formal epistatic analyses to address the role of OPA1 in TNBC proliferation, migration, and invasion in vitro and in vivo. RESULTS We identified a signature of OPA1 upregulation in breast cancer that correlates with worse prognosis. Accordingly, OPA1 inhibition could reduce breast cancer cells proliferation, migration, and invasion in vitro and in vivo. Mechanistically, while OPA1 silencing did not reduce mitochondrial respiration, it increased levels of miRNAs of the 148/152 family known to inhibit tumor growth and invasiveness. Indeed, these miRNAs were epistatic to OPA1 in the regulation of TNBC cells growth and invasiveness. CONCLUSIONS Our data show that targeted inhibition of the mitochondrial fusion protein OPA1 curtails TNBC growth and nominate OPA1 as a druggable target in TNBC.
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Affiliation(s)
- Margherita Zamberlan
- Department of Biology, University of Padova, Via U. Bassi 58B, 35121, Padova, Italy
- Veneto Institute of Molecular Medicine, Via Orus 2, 35129, Padova, Italy
| | - Amandine Boeckx
- Laboratory of molecular angiogenesis, GIGA-Research, Avenue de l'Hôpital, 1, 4020, Liège, Belgium
| | - Florian Muller
- Laboratory of molecular angiogenesis, GIGA-Research, Avenue de l'Hôpital, 1, 4020, Liège, Belgium
| | - Federica Vinelli
- Department of Biology, University of Padova, Via U. Bassi 58B, 35121, Padova, Italy
- Veneto Institute of Molecular Medicine, Via Orus 2, 35129, Padova, Italy
| | - Olivier Ek
- Department of Biology, University of Padova, Via U. Bassi 58B, 35121, Padova, Italy
| | - Caterina Vianello
- Department of Biology, University of Padova, Via U. Bassi 58B, 35121, Padova, Italy
| | - Emeline Coart
- Laboratory of molecular angiogenesis, GIGA-Research, Avenue de l'Hôpital, 1, 4020, Liège, Belgium
| | - Keitaro Shibata
- Department of Biology, University of Padova, Via U. Bassi 58B, 35121, Padova, Italy
- Veneto Institute of Molecular Medicine, Via Orus 2, 35129, Padova, Italy
| | - Aurélie Christian
- Laboratory of molecular angiogenesis, GIGA-Research, Avenue de l'Hôpital, 1, 4020, Liège, Belgium
| | - Francesca Grespi
- Department of Biology, University of Padova, Via U. Bassi 58B, 35121, Padova, Italy
- Veneto Institute of Molecular Medicine, Via Orus 2, 35129, Padova, Italy
| | - Marta Giacomello
- Department of Biology, University of Padova, Via U. Bassi 58B, 35121, Padova, Italy
| | - Ingrid Struman
- Laboratory of molecular angiogenesis, GIGA-Research, Avenue de l'Hôpital, 1, 4020, Liège, Belgium
| | - Luca Scorrano
- Department of Biology, University of Padova, Via U. Bassi 58B, 35121, Padova, Italy.
- Veneto Institute of Molecular Medicine, Via Orus 2, 35129, Padova, Italy.
| | - Stéphanie Herkenne
- Laboratory of molecular angiogenesis, GIGA-Research, Avenue de l'Hôpital, 1, 4020, Liège, Belgium.
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11
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Xu C, Zhou G, Sun Z, Zhang Z, Zhao H, Jiang X. miR-148a-3p inhibits the proliferation and migration of bladder cancer via regulating the expression of ROCK-1. PeerJ 2022; 10:e12724. [PMID: 35127282 PMCID: PMC8800387 DOI: 10.7717/peerj.12724] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 12/10/2021] [Indexed: 01/12/2023] Open
Abstract
PURPOSE To investigate the mechanism of miR-148a-3p regulating the proliferation and migration of bladder tumor cells. MATERIALS AND METHODS We conducted a preliminary study to detect the relative expression of miR-148a-3p in bladder cancer and para-cancerous tissue samples. Three bladder tumor cell lines, T24, 5,637 and UM-UC-3, were selected. The expression levels of miR-148a-3p were artificially regulated with miR-148a-3p mimics and the miR-148a-3p inhibitor. The relative expression levels of miR-148a-3p in the samples of each cell line were determined. Cell Counting Kit-8 (CCK-8) was used to detect cell proliferation, while the effect of the miR-148a-3p mimics and inhibitor on tumor cell migration was detected by wound healing assay. Flow cytometry assay was carried out to explore the effect of miR-148a-3p on cell apoptosis. Dual-luciferase reporter assay was performed in order to verify miR-148a-3p's target gene. The expressions of ROCK-1 and Bcl-2 were analyzed by western blot. RESULTS The relative expression of miR-148a-3p in tumor and adjacent tissues was assessed with qRT-PCR (P < 0.05) and found to be significantly lower in the tumor tissues than the adjacent tissues. The data obtained from the CCK-8 and wound healing assay showed that intracellular transfection of miR-148a-3p mimics could inhibit cell proliferation and migration, while the miR-148a-3p inhibitor promoted them. Overexpression of miR-148a-3p promoted cell apoptosis in the T24 and 5,637 cell lines. The dual-luciferase reporter assay verified that ROCK-1 is a direct target of miR-148a-3p. Western blot showed that miR-148a-3p overexpression downregulated the expression of ROCK-1 and Bcl-2, while miR-148a-3p knockdown upregulated the expression of ROCK-1 and Bcl-2. CONCLUSIONS We confirmed that miR-148a-3p was significantly decreased in bladder cancer cells. miR-148a-3p overexpression inhibited bladder cancer cell proliferation and migration, whereas miR-148a-3p knockdown promoted bladder cancer cell proliferation and migration. Moreover, we found that ROCK-1 was a downstream target of miR-148a-3p. We also found that miR-148a-3p induced cell apoptosis by regulating the expression of Bcl-2. However, the deeper mechanism of this regulatory relationship needs further study.
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Affiliation(s)
- Chao Xu
- Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Guanwen Zhou
- Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Zhuang Sun
- Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Zhaocun Zhang
- Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Haifeng Zhao
- Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xianzhou Jiang
- Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
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12
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Peng X, Chen G, Lv B, Lv J. MicroRNA-148a/152 cluster restrains tumor stem cell phenotype of colon cancer via modulating CCT6A. Anticancer Drugs 2022; 33:e610-e621. [PMID: 34486532 DOI: 10.1097/cad.0000000000001198] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Accumulating evidence has presented that microRNA-148a/152 (miR-148a/152) acts as the tumor inhibitor in various cancers. In this article, we aimed to probe the inhibition of colon cancer stem cells by miR-148a/152 cluster via regulation of CCT6A. miR-148a/152 and CCT6A expression in colon cancer tissues and cells was detected. The relationship between miR-148a/152 expression and the clinicopathological features of patients with colon cancer was analyzed. Colon cancer stem cells (CD44+/CD133+) were selected and high/low expression of miR-148a/152 plasmids were synthesized to intervene CD44+/CD133+ colon cancer stem cells to investigate the function of miR-148a/152 in invasion, migration, proliferation, colony formation and apoptosis of cells. The growth status of nude mice was observed to verify the in-vitro results. The relationship between miR-148a/152 and CCT6A was analyzed. CCT6A upregulated and miR-148a/152 downregulated in colon cancer tissues. MiR-148a/152 expression was correlated with tumor node metastasis stage, lymph node metastasis and differentiation degree. Upregulated miR-148a/152 depressed CCT6A expression and restrained invasion and migration ability, colony formation and proliferation, induced cell apoptosis, depressed OCT4, Nanog and SOX2 mRNA expression of colon cancer stem cells, and descended tumor weight and volume in nude mice. CCT6A was a target gene of miR-148a/152. Overexpression of CCT6A protected colon cancer stem cells. Functional studies showed that upregulation of miR-148a/152 can suppress the migration, invasion and proliferation of CD44+/CD133+ colon cancer stem cells, advance its apoptosis via inhibition of CCT6A expression.
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Affiliation(s)
- Xin Peng
- Department of Anorectal Surgery, Xinxiang Central Hospital General Surgery III, Xinxiang City, Henan, China
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13
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Song G, Ma Y, Ma Y, Liu P, Hou L, Xu Z, Jiang J, Shen Y, Cao Y, Zhao Y. MiR-335-5p Targets SDC1 to Regulate Progression of Breast Cancer. Crit Rev Eukaryot Gene Expr 2022; 32:21-31. [DOI: 10.1615/critreveukaryotgeneexpr.2022041813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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14
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Tang K, Wu Z, Sun M, Huang X, Sun J, Shi J, Wang X, Miao Z, Gao P, Song Y, Wang Z. Elevated MMP10/13 mediated barrier disruption and NF-κB activation aggravate colitis and colon tumorigenesis in both individual or full miR-148/152 family knockout mice. Cancer Lett 2022; 529:53-69. [PMID: 34979166 DOI: 10.1016/j.canlet.2021.12.033] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 12/07/2021] [Accepted: 12/28/2021] [Indexed: 12/13/2022]
Abstract
Dynamic miRNA alteration is known to occur in colitis-associated colon cancer (CAC), while the molecular mechanisms underpinning how miRNAs modulate the development from chronic inflammation to CAC is lacking. For the first time, we constructed knockout (KO) mice for individual miR-148/152 family members and entire miR-148/152 family. Based on these KO mice, we conduct the first comprehensive analysis of miR-148/152 family, demonstrating that deficiency of any member of miR-148/152 family aggravate colitis and CAC. Loss of individual miR-148/152 family members or full-family enhance MMP10 and MMP13 expression, causing disruption of intestinal barrier and cleaving pro-TNF-α into bioactive TNF-α fragments to activate NF-κB signaling, thereby aggravating colitis. Individual and full-family deletion also increase accumulation of IKKα and IKKβ, resulting in further hyperactivation of NF-κB signaling, exacerbating colitis and CAC. Moreover, blocking NF-κB signaling exerts a restorative effect on colitis and CAC models only in KO mice. Taken together, these findings demonstrate deleting the full miR-148/152 family or individual members exhibit similar effects in colitis and CAC. Mechanically, miR-148/152 family members deficiency in mice elevates MMP10 and MMP13 to accelerate colitis and CAC via disrupting intestinal barrier function and activating NF-κB signaling, suggesting a potential therapeutic strategy for colitis and CAC.
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Affiliation(s)
- Kaiwen Tang
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, 155 North Nanjing Street, Heping District, Shenyang, 110001, China
| | - Zhonghua Wu
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, 155 North Nanjing Street, Heping District, Shenyang, 110001, China
| | - Mingwei Sun
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, 155 North Nanjing Street, Heping District, Shenyang, 110001, China
| | - Xuanzhang Huang
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, 155 North Nanjing Street, Heping District, Shenyang, 110001, China
| | - Jingxu Sun
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, 155 North Nanjing Street, Heping District, Shenyang, 110001, China
| | - Jinxin Shi
- Department of Gastrointestinal Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
| | - Xin Wang
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, 155 North Nanjing Street, Heping District, Shenyang, 110001, China
| | - Zhifeng Miao
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, 155 North Nanjing Street, Heping District, Shenyang, 110001, China
| | - Peng Gao
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, 155 North Nanjing Street, Heping District, Shenyang, 110001, China.
| | - Yongxi Song
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, 155 North Nanjing Street, Heping District, Shenyang, 110001, China.
| | - Zhenning Wang
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, 155 North Nanjing Street, Heping District, Shenyang, 110001, China
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15
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Abdelbaky I, Tayara H, Chong KT. Identification of miRNA-Small Molecule Associations by Continuous Feature Representation Using Auto-Encoders. Pharmaceutics 2021; 14:pharmaceutics14010003. [PMID: 35056899 PMCID: PMC8780428 DOI: 10.3390/pharmaceutics14010003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/17/2021] [Accepted: 12/18/2021] [Indexed: 12/17/2022] Open
Abstract
MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in the body and affect various diseases, including cancers. Controlling miRNAs with small molecules is studied herein to provide new drug repurposing perspectives for miRNA-related diseases. Experimental methods are time- and effort-consuming, so computational techniques have been applied, relying mostly on biological feature similarities and a network-based scheme to infer new miRNA–small molecule associations. Collecting such features is time-consuming and may be impractical. Here we suggest an alternative method of similarity calculation, representing miRNAs and small molecules through continuous feature representation. This representation is learned by the proposed deep learning auto-encoder architecture. Our suggested representation was compared to previous works and achieved comparable results using 5-fold cross validation (92% identified within top 25% predictions), and better predictions for most of the case studies (avg. of 31% vs. 25% identified within the top 25% of predictions). The results proved the effectiveness of our proposed method to replace previous time- and effort-consuming methods.
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Affiliation(s)
- Ibrahim Abdelbaky
- Artificial Intelligence Department, Faculty of Computers and Artificial Intelligence, Benha University, Banha 13518, Egypt;
| | - Hilal Tayara
- School of International Engineering and Science, Jeonbuk National University, Jeonju 54896, Korea
- Correspondence: (H.T.); (K.T.C.); Tel.: +82-63-270-2478 (K.T.C.)
| | - Kil To Chong
- Department of Electronics and Information Engineering, Jeonbuk National University, Jeonju 54896, Korea
- Advanced Electronics and Information Research Center, Jeonbuk National University, Jeonju 54896, Korea
- Correspondence: (H.T.); (K.T.C.); Tel.: +82-63-270-2478 (K.T.C.)
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16
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Cheng L, Li Q, Tan B, Ma D, Du G. Diagnostic value of microRNA-148/152 family in non-small-cell lung cancer (NSCLC): A systematic review and meta-analysis. Medicine (Baltimore) 2021; 100:e28061. [PMID: 35049226 PMCID: PMC9191337 DOI: 10.1097/md.0000000000028061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 10/16/2021] [Accepted: 11/11/2021] [Indexed: 11/26/2022] Open
Abstract
BACKGROUNDS Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer with extremely high morbidity and mortality. OBJECTIVE To evaluate the diagnostic value of the blood miR-148/152 family to NSCLC by meta-analysis. METHODS PubMed, Embase (via Ovid), The Cochrane Library, web of science, and Chinese National Knowledge Infrastructure were retrieved using miR-148, miR-152, and NSCLC as search terms for studies about miR-148/152 family in the diagnosis of NSCLC, the quality assessment of diagnostic accuracy studies was adopted to evaluate the quality of literature, STATA 12.0 and Meta-Disc 1.4 were used to conduct meta-analysis and to probe the clinical utility (with plotting the Fagan Nomogram). RESULTS A total 2145 cases in 8 trials published in 4 studies finally enrolled for final analysis. The area under the curve of the summary receiver operating characteristic was 0.87 [0.83-0.89], the pooled sensitivity was 0.79 [0.74, 0.83], the pooled specificity was 0.81 [0.76, 0.85] and the diagnosis odds ratio was 15.53 [10.88-22.17], the integrated positive likelihood ratio was 4.1 [3.30, 5.20] and the integrated negative likelihood ratio was 0.27 [0.22, 0.33]. CONCLUSION Current evidence indicated that miR-148/152 family might be served as novel non-invasive diagnostic biomarkers for NSCLC diagnosis with good sensitivity and specificity. it still needs more research with high quality, large sample sizes, and multiple centers for further verification.
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Affiliation(s)
- Long Cheng
- Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Qinyun Li
- Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Bangxian Tan
- Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Daiyuan Ma
- Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Guobo Du
- Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
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17
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Dougherty U, Mustafi R, Zhu H, Zhu X, Deb D, Meredith SC, Ayaloglu-Butun F, Fletcher M, Sanchez A, Pekow J, Deng Z, Amini N, Konda VJ, Rao VL, Sakuraba A, Kwesi A, Kupfer SS, Fichera A, Joseph L, Hart J, He F, He TC, West-Szymanski D, Li YC, Bissonnette M. Upregulation of polycistronic microRNA-143 and microRNA-145 in colonocytes suppresses colitis and inflammation-associated colon cancer. Epigenetics 2021; 16:1317-1334. [PMID: 33356812 PMCID: PMC8813074 DOI: 10.1080/15592294.2020.1863117] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 11/08/2020] [Accepted: 12/07/2020] [Indexed: 12/25/2022] Open
Abstract
Because ADAM17 promotes colonic tumorigenesis, we investigated potential miRNAs regulating ADAM17; and examined effects of diet and tumorigenesis on these miRNAs. We also examined pre-miRNA processing and tumour suppressor roles of several of these miRNAs in experimental colon cancer. Using TargetScan, miR-145, miR-148a, and miR-152 were predicted to regulate ADAM17. miR-143 was also investigated as miR-143 and miR-145 are co-transcribed and associated with decreased tumour growth. HCT116 colon cancer cells (CCC) were co-transfected with predicted ADAM17-regulating miRNAs and luciferase reporters controlled by ADAM17-3'UTR. Separately, pre-miR-143 processing by colonic cells was measured. miRNAs were quantified by RT-PCR. Tumours were induced with AOM/DSS in WT and transgenic mice (Tg) expressing pre-miR-143/miR-145 under villin promoter. HCT116 transfection with miR-145, -148a or -152, but not scrambled miRNA inhibited ADAM17 expression and luciferase activity. The latter was suppressed by mutations in ADAM17-3'UTR. Lysates from colonocytes, but not CCC, processed pre-miR-143 and mixing experiments suggested CCC lacked a competency factor. Colonic miR-143, miR-145, miR-148a, and miR-152 were downregulated in tumours and more moderately by feeding mice a Western diet. Tg mice were resistant to DSS colitis and had significantly lower cancer incidence and tumour multiplicity. Tg expression blocked up-regulation of putative targets of miR-143 and miR-145, including ADAM17, K-Ras, XPO5, and SET. miR-145, miR-148a, and miR-152 directly suppress colonocyte ADAM17 and are down-regulated in colon cancer. This is the first direct demonstration of tumour suppressor roles for miR-143 and miR-145 in an in vivo model of colonic tumorigenesis.
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Affiliation(s)
| | - Reba Mustafi
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Hongyan Zhu
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Xiaorong Zhu
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Dilip Deb
- Department of Medicine, University of Chicago, Chicago IL, USA
| | | | | | | | - Arantxa Sanchez
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Joel Pekow
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Zifeng Deng
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Nader Amini
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Vani J Konda
- Department of Medicine, Baylor University, Dallas, TX, USA
| | - Vijaya L. Rao
- Department of Medicine, University of Chicago, Chicago IL, USA
| | | | - Akushika Kwesi
- Department of Medicine, University of Chicago, Chicago IL, USA
| | - Sonia S Kupfer
- Department of Medicine, University of Chicago, Chicago IL, USA
| | | | - Loren Joseph
- Departments of Pathology, Beth Israel, Harvard Medical School, Boston, MA, USA
| | - John Hart
- Departments of Pathology, University of Chicago, Chicago IL, USA
| | - Fang He
- Departments of Orthopedics, The University of Chicago, Chicago, IL, USA
| | - Tong-Chuan He
- Departments of Orthopedics, The University of Chicago, Chicago, IL, USA
| | | | - Yan Chun Li
- Department of Medicine, University of Chicago, Chicago IL, USA
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18
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Yang B, Huang S, Chen H, Li R, Hou S, Zhao J, Li Y. DNMT3B regulates proliferation of A549 cells through the microRNA-152-3p/NCAM1 pathway. Oncol Lett 2021; 23:11. [PMID: 34820010 PMCID: PMC8607351 DOI: 10.3892/ol.2021.13129] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 10/04/2021] [Indexed: 11/17/2022] Open
Abstract
The purpose of the present study was to examine the epigenetic mechanism by which microRNA (miR)-152-3p regulates proliferation in non-small cell lung cancer A549 cells via neural cell adhesion molecule 1 (NCAM1). Bisulfite sequencing PCR (BSP), the gold standard for methylation detection, uses bisulfite-treated DNA to determine its pattern of methylation. Treatment of DNA with bisulfite converts cytosine residues to uracil, but leaves 5-methylcytosine residues unaffected. It was conducted and demonstrated a relatively high level of methylation in the miR-152-3p promoter region. Chromatin immunoprecipitation was combined with PCR to detect the binding of DNA methyltransferase 3B (DNMT3B) protein to miR-152-3p, which tends to occur in the core region of the miR-152-3p gene in A549 cells. Luciferase assay identified NCAM1 as the target gene of miR-152-3p. MTT, colony formation and Transwell assays indicated that miR-152-3p could decrease cell proliferation and invasion and in addition to reducing the expression level of NCAM1. Overexpression of NCAM1 could attenuate the effect of miR-152-3p. DNMT3B knockdown decreased the proliferative ability of A549 cells and increased the expression of miR-152-3p, while decreased that of NCAM1. After treatment with miR-152-3p inhibitor, these effects were attenuated and the NCAM1 expression level was upregulated. The results indicated that miR-152-3p may suppress the proliferation of A549 cells by downregulating NCAM1. In addition, DNMT3B negatively regulated the expression of miR-152-3p via modulation of the methylation level in the miR-152-3p core region, thus mediating the proliferation of lung tumor cells.
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Affiliation(s)
- Bo Yang
- Department of Oncology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang Autonomous Region 533000, P.R. China
| | - Shiqing Huang
- Department of Oncology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang Autonomous Region 533000, P.R. China
| | - Hongming Chen
- Department of Cardiothoracic Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang Autonomous Region 533000, P.R. China
| | - Rizhu Li
- Department of Cardiothoracic Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang Autonomous Region 533000, P.R. China
| | - Shihao Hou
- Department of Oncology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang Autonomous Region 533000, P.R. China
| | - Jingjing Zhao
- Department of Oncology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang Autonomous Region 533000, P.R. China
| | - Yepeng Li
- Department of Oncology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang Autonomous Region 533000, P.R. China
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Cheng X, Wei H, Zhang S, Zhang F. Predictive and Prognostic Value of an MicroRNA Signature for Gastric Carcinoma Undergoing Adjuvant Chemotherapy. DNA Cell Biol 2021; 40:1428-1444. [PMID: 34767733 DOI: 10.1089/dna.2021.0377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Gastric carcinoma (GC) is one of the most common cause of tumor-related death. Chemotherapy resistance usually occurs, leading to cancer relapse and poor survival of GC patients. To investigate the role of miRNAs in chemotherapy resistance for GC patients, we conducted an integrated analysis of miRNA expression and survival information using data obtained from The Cancer Genome Atlas project. Genome-wide screening of chemotherapy response-specific miRNAs was performed using Cox proportional hazards regression analyses for patients who received chemotherapy or those who had never received chemotherapy, respectively. A four-miRNA expression signature (involving two protective miRNAs, miR-200b and miR-103a, and two risk ones miR-199 and miR-152) was predicted as a specific indicator for GC chemoresistance (p = 0.00053; hazard ratio = 8.63), outperforming those clinicopathological factors. Functional experiments confirmed the roles of these signature miRNAs in regulation of chemotherapy response. Functional enrichment of these signature miRNAs and risk score revealed positive association with epithelial-mesenchymal transition (EMT), and negative association with cell cycle checkpoint and DNA damage response. Furthermore, the immune infiltration-miRNA functional network analysis revealed transformation from activated effector cells to resting immunosuppressive cells are preferred in GCs with adverse chemotherapy response. In summary, our work identifies a four-miRNA expression signature as a promising chemoresistance biomarker in GC, which provides novel insights into developing new strategies to overcome GC chemoresistance.
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Affiliation(s)
- Xiaowei Cheng
- Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi City, People's Republic of China
| | - Hongkuang Wei
- The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning City, People's Republic of China
| | - Sheng Zhang
- Wuxi Eighth People's Hospital, Wuxi City, People's Republic of China
| | - Fuzheng Zhang
- Department of Radiation Oncology, Affiliated Hospital of Jiangnan University, Wuxi City, People's Republic of China
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Choi Y, Kim B, Ham S, Chung S, Maeng S, Kim HS, Im HI. Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis. PLoS One 2021; 16:e0256390. [PMID: 34437591 PMCID: PMC8389495 DOI: 10.1371/journal.pone.0256390] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 08/05/2021] [Indexed: 12/14/2022] Open
Abstract
Ketamine is a dissociative anesthetic and a non-competitive NMDAR antagonist. At subanesthetic dose, ketamine can relieve pain and work as a fast-acting antidepressant, but the underlying molecular mechanism remains elusive. This study aimed to investigate the mode of action underlying the effects of acute subanesthetic ketamine treatment by bioinformatics analyses of miRNAs in the medial prefrontal cortex of male C57BL/6J mice. Gene Ontology and KEGG pathway analyses of the genes putatively targeted by ketamine-responsive prefrontal miRNAs revealed that acute subanesthetic ketamine modifies ubiquitin-mediated proteolysis. Validation analysis suggested that miR-148a-3p and miR-128-3p are the main players responsible for the subanesthetic ketamine-mediated alteration of ubiquitin-mediated proteolysis through varied regulation of ubiquitin ligases E2 and E3. Collectively, our data imply that the prefrontal miRNA-dependent modulation of ubiquitin-mediated proteolysis is at least partially involved in the mode of action by acute subanesthetic ketamine treatment.
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Affiliation(s)
- Yunjung Choi
- Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul, South Korea
- Department of Pharmacology, College of Medicine, Seoul National University, Seoul, South Korea
| | - Baeksun Kim
- Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul, South Korea
- Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, South Korea
| | - Suji Ham
- Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul, South Korea
- Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, South Korea
| | - Sooyoung Chung
- Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul, South Korea
| | - Sungho Maeng
- College of East-West Medical Science, Kyung Hee University, Yongin, South Korea
| | - Hye-Sun Kim
- Department of Pharmacology, College of Medicine, Seoul National University, Seoul, South Korea
- Department of Pharmacology, Seoul National University Bundang Hospital, Seongnam, Bundang-Gu, South Korea
| | - Heh-In Im
- Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul, South Korea
- Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, South Korea
- Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul, South Korea
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21
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Khajehnoori S, Zarei F, Mazaheri M, Dehghani-Firoozabadi A. Epidrug Modulated Expression of MiR--152 and MiR-148a Reverse Cisplatin Resistance in Ovarian Cancer Cells: An Experimental In-vitro Study. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH : IJPR 2021; 19:509-519. [PMID: 33680048 PMCID: PMC7757992 DOI: 10.22037/ijpr.2020.15450.13217] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Cisplatin is a common agent which is used to treat Epithelial Ovarian Cancer (EOC), but cisplatin resistance is a major obstacle in successful treatment of ovarian cancer. Aberration in epigenetic changes play an important role in disregulation of gene expression. MiR-152 and miR-148a are frequently down-regulated in EOC due to promoter hyper-methylation. DNA methyltransferase1 (DNMT1), the main enzyme in maintenance of the pattern of DNA methylation, is one of the targets of miR-152 and miR-148a. Aberrantly up-regulation of DNMT1 is responsible for silencing of tumor suppressor genes in carcinogenesis. We hypothesized that re-expression of miR-152 and miR-148a and consequently down-regulation of DNMT1 may resensitize cancerous cells to chemotherapeutics agents. The aim of the present study is to investigate the effect of 5-azacytidine (5-Aza) and Trichostatin A on miR-152 and miR-148a expression in A2780CP ovarian cancer cell line. Optimal doses of 5-Azacitidine and TSA were measured by 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A2780CP cell line was treated by each drugs, alone or in combination and the expression of miR-148a, miR-152 and DNMT1 was evaluated by Real-Time Quantitative Reverse Transcription-Polymerase Chain Reaction (RT-qPCR). The results revealed that TSA and 5-Azacytidine are able to revive the expression of miR-148a and miR-152 genes and mediate growth inhibition of epithelial ovarian cancer cells. The present study suggests that re-expression of miR-148a and miR-152 by epigenetic therapy aiming to DNMT1 suppression might resensitize resistant ovarian tumors to conventional chemotherapy.
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Affiliation(s)
- Sahel Khajehnoori
- Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences,Yazd, Iran.,S. K. and F. Z. contributed equally to this work
| | - Fatemeh Zarei
- Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences,Yazd, Iran.,S. K. and F. Z. contributed equally to this work
| | - Mahta Mazaheri
- Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences,Yazd, Iran.,Mother and Newborn Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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22
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Favier A, Rocher G, Larsen AK, Delangle R, Uzan C, Sabbah M, Castela M, Duval A, Mehats C, Canlorbe G. MicroRNA as Epigenetic Modifiers in Endometrial Cancer: A Systematic Review. Cancers (Basel) 2021; 13:cancers13051137. [PMID: 33800944 PMCID: PMC7961497 DOI: 10.3390/cancers13051137] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 02/02/2021] [Accepted: 03/01/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Endometrial cancer (EC) is the 2nd most common gynecologic cancer worldwide. MicroRNAs (miRNAs) are small noncoding RNAs that contribute to epigenetic regulation. The objective of this systematic review is to summarize our current knowledge on the role of miRNAs in the epigenetic deregulation of tumor-related genes in EC. It includes all miRNAs reported to be involved in EC including their roles in DNA methylation and RNA-associated silencing. This systematic review should be useful for development of novel strategies to improve diagnosis and risk assessment as well as for new treatments aimed at miRNAs, their target genes or DNA methylation. Abstract The objective of this systematic review is to summarize our current knowledge on the influence of miRNAs in the epigenetic deregulation of tumor-related genes in endometrial cancer (EC). We conducted a literature search on the role of miRNAs in the epigenetic regulation of EC applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following terms were used: microRNA, miRNA, miR, endometrial cancer, endometrium, epigenetic, epimutation, hypermethylation, lynch, deacetylase, DICER, novel biomarker, histone, chromatin. The miRNAs were classified and are presented according to their function (tumor suppressor or onco-miRNA), their targets (when known), their expression levels in EC tissue vs the normal surrounding tissue, and the degree of DNA methylation in miRNA loci and CpG sites. Data were collected from 201 articles, including 190 original articles, published between November 1, 2008 and September 30, 2020 identifying 313 different miRNAs implicated in epigenetic regulation of EC. Overall, we identified a total of 148 miRNAs with decreased expression in EC, 140 miRNAs with increased expression in EC, and 22 miRNAs with discordant expression levels. The literature implicated different epigenetic phenomena including altered miRNA expression levels (miR-182, -230), changes in the methylation of miRNA loci (miR-34b, -129-2, -130a/b, -152, -200b, -625) and increased/decreased methylation of target genes (miR-30d,-191). This work provides an overview of all miRNAs reported to be involved in epigenetic regulation in EC including DNA methylation and RNA-associated silencing. These findings may contribute to novel strategies in diagnosis, risk assessment, and treatments aimed at miRNAs, their target genes or DNA methylation.
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Affiliation(s)
- Amélia Favier
- Centre de Recherche Saint-Antoine (CRSA), INSERM UMR_S_938, Cancer Biology and Therapeutics, Sorbonne University, 75012 Paris, France; (A.K.L.); (C.U.); (M.S.)
- Department of Gynecological and Breast Surgery and Oncology, Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris (AP-HP), University Hospital, 75013 Paris, France; (G.R.); (R.D.)
- Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, Unité Mixte de Recherche Scientifique 938 and SIRIC CURAMUS, INSERM, Sorbonne Université, 75012 Paris, France;
- Correspondence: (A.F.); (G.C.)
| | - Grégoire Rocher
- Department of Gynecological and Breast Surgery and Oncology, Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris (AP-HP), University Hospital, 75013 Paris, France; (G.R.); (R.D.)
- Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, Unité Mixte de Recherche Scientifique 938 and SIRIC CURAMUS, INSERM, Sorbonne Université, 75012 Paris, France;
| | - Annette K. Larsen
- Centre de Recherche Saint-Antoine (CRSA), INSERM UMR_S_938, Cancer Biology and Therapeutics, Sorbonne University, 75012 Paris, France; (A.K.L.); (C.U.); (M.S.)
| | - Romain Delangle
- Department of Gynecological and Breast Surgery and Oncology, Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris (AP-HP), University Hospital, 75013 Paris, France; (G.R.); (R.D.)
| | - Catherine Uzan
- Centre de Recherche Saint-Antoine (CRSA), INSERM UMR_S_938, Cancer Biology and Therapeutics, Sorbonne University, 75012 Paris, France; (A.K.L.); (C.U.); (M.S.)
- Department of Gynecological and Breast Surgery and Oncology, Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris (AP-HP), University Hospital, 75013 Paris, France; (G.R.); (R.D.)
| | - Michèle Sabbah
- Centre de Recherche Saint-Antoine (CRSA), INSERM UMR_S_938, Cancer Biology and Therapeutics, Sorbonne University, 75012 Paris, France; (A.K.L.); (C.U.); (M.S.)
| | - Mathieu Castela
- Scarcell Therapeutics, 101 rue de Sèvres, 75006 Paris, France;
| | - Alex Duval
- Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, Unité Mixte de Recherche Scientifique 938 and SIRIC CURAMUS, INSERM, Sorbonne Université, 75012 Paris, France;
| | - Céline Mehats
- U1016, CNRS, UMR8104, Institut Cochin, INSERM, Université de Paris, 75014 Paris, France;
| | - Geoffroy Canlorbe
- Centre de Recherche Saint-Antoine (CRSA), INSERM UMR_S_938, Cancer Biology and Therapeutics, Sorbonne University, 75012 Paris, France; (A.K.L.); (C.U.); (M.S.)
- Department of Gynecological and Breast Surgery and Oncology, Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris (AP-HP), University Hospital, 75013 Paris, France; (G.R.); (R.D.)
- Correspondence: (A.F.); (G.C.)
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23
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Tang M, Wang Q, Wang K, Wang F. Mesenchymal stem cells-originated exosomal microRNA-152 impairs proliferation, invasion and migration of thyroid carcinoma cells by interacting with DPP4. J Endocrinol Invest 2020; 43:1787-1796. [PMID: 32876927 DOI: 10.1007/s40618-020-01406-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 08/23/2020] [Indexed: 01/19/2023]
Abstract
BACKGROUND Thyroid carcinoma (THCA) is the most prevalent tumor in the endocrine system with an increasing incidence. Recent studies have underscored the function of microRNAs (miRNAs) in THCA. Nevertheless, knowledge regarding the effects of exosomal miRNAs in THCA is still limited. This report intended to probe the regulatory effects of exosomal miR-152 on THCA and the underlying mechanism. METHODS The expression profile of miR-152 was studied in clinical samples as well as B-CPAP and TPC-1 cells. Transwell, CCK-8, and flow cytometric assays were performed to investigate the roles of miR-152 on invasion, migration, proliferation, and apoptosis in B-CPAP and TPC-1 cells. The putative target of miR-152 was predicted using the bioinformatic analysis, and the targeting relationship was confirmed verified subsequently. Afterward, exosomes were isolated from bone marrow mesenchymal stem cells (BM-MSCs) and co-cultured with B-CPAP and TPC-1 cells to explore the function of exosomal miR-152 on THCA cells. RESULTS miR-152 was reduced in THCA tissues and cells. Restoration of miR-152 inhibited proliferation, invasion and migration of B-CPAP and TPC-1 cells, but promoted cell apoptosis. Dipeptidyl dipeptidase 4 (DPP4), a target of miR-152, was found to promote THCA cell invasion and migration. miR-152 ferried by BM-MSCs-derived exosomes repressed THCA cell invasion and migration, and pcDNA-DPP4 weakened the repression effect. CONCLUSION Exosomal miR-152 inhibited proliferation, migration and invasion of THCA cells by binding with DPP4, which may represent a novel target for the treatment of THCA.
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Affiliation(s)
- M Tang
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Q Wang
- Department of Rehabilitation, The First Affiliated Hospital of Chengdu Medical College, No. 278, Middle Section of Baoguang Avenue, Xindu District, Chengdu, 610500, Sichuan, China
| | - K Wang
- Department of Rehabilitation, The First Affiliated Hospital of Chengdu Medical College, No. 278, Middle Section of Baoguang Avenue, Xindu District, Chengdu, 610500, Sichuan, China.
| | - F Wang
- Department of Rehabilitation, The First Affiliated Hospital of Chengdu Medical College, No. 278, Middle Section of Baoguang Avenue, Xindu District, Chengdu, 610500, Sichuan, China.
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24
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Zhai K, Liu B, Gao L. Long-Noncoding RNA TUG1 Promotes Parkinson's Disease via Modulating MiR-152-3p/PTEN Pathway. Hum Gene Ther 2020; 31:1274-1287. [PMID: 32808542 DOI: 10.1089/hum.2020.106] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Kaihua Zhai
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Boyu Liu
- Department of Endocrine, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Lin Gao
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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25
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Integrative p53, micro-RNA and Cathepsin Protease Co-Regulatory Expression Networks in Cancer. Cancers (Basel) 2020; 12:cancers12113454. [PMID: 33233599 PMCID: PMC7699684 DOI: 10.3390/cancers12113454] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/05/2020] [Accepted: 11/18/2020] [Indexed: 12/12/2022] Open
Abstract
Simple Summary This article describes an emerging area of significant interest in cancer and cell death and the relationships shared by these through the transcriptional regulation of cathepsin protease genes by micro-RNAs that are connected to p53 activation. While it has been demonstrated that the p53 protein can directly regulate some cathepsin genes and the expression of their upstream regulatory micro-RNAs, very little is known about what input the p53 isoform proteins may have in regulating this relationship. Herein, we draw attention to this important regulatory aspect in the context of describing mechanisms that are being established for the micro-RNA regulation of cathepsin protease genes and their collective use in diagnostic or prognostic assays. Abstract As the direct regulatory role of p53 and some of its isoform proteins are becoming established in modulating gene expression in cancer research, another aspect of this mode of gene regulation that has captured significant interest over the years is the mechanistic interplay between p53 and micro-RNA transcriptional regulation. The input of this into modulating gene expression for some of the cathepsin family members has been viewed as carrying noticeable importance based on their biological effects during normal cellular homeostasis and cancer progression. While this area is still in its infancy in relation to general cathepsin gene regulation, we review the current p53-regulated micro-RNAs that are generating significant interest through their regulation of cathepsin proteases, thereby strengthening the link between activated p53 forms and cathepsin gene regulation. Additionally, we extend our understanding of this developing relationship to how such micro-RNAs are being utilized as diagnostic or prognostic tools and highlight their future uses in conjunction with cathepsin gene expression as potential biomarkers within a clinical setting.
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26
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Wang C, Ma X, Zhang J, Jia X, Huang M. DNMT1 maintains the methylation of miR-152-3p to regulate TMSB10 expression, thereby affecting the biological characteristics of colorectal cancer cells. IUBMB Life 2020; 72:2432-2443. [PMID: 32918845 PMCID: PMC7693087 DOI: 10.1002/iub.2366] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 07/20/2020] [Accepted: 07/28/2020] [Indexed: 12/13/2022]
Abstract
Objective DNA methyltransferases (DNMTs) take on a relevant role in epigenetic control of cancer proliferation and cell survival. However, the molecular mechanisms underlying the establishment and maintenance of DNA methylation in human cancer remain to be fully elucidated. This study was to investigate that how DNMT1 affected the biological characteristics of colorectal cancer (CRC) cells via modulating methylation of microRNA (miR)‐152‐3p and thymosin β 10 (TMSB10) expression. Methods DNMT1, miR‐152‐3p, and TMSB10 expression, and the methylation of miR‐152‐3p in CRC tissues and cells were detected. SW‐480 and HCT‐116 CRC cells were transfected with DNMT1 or miR‐152‐3p‐related sequences or plasmids to explore their characters in biological functions of CRC cells. The binding relationship between DNMT1 and miR‐152‐3p and the targeting relationship between miR‐152‐3p and TMSB10 were analyzed. The tumor growth was also detected in vivo. Results Upregulated DNMT1, TMSB10, reduced miR‐152‐3p, and methylated miR‐152‐3p were detected in CRC tissues and cells. Silenced DNMT1 or upregulated miR‐152‐3p reduced TMSB10 expression and suppressed CRC progression and tumor growth. Moreover, elevated DNMT1 could reverse the effect of miR‐152‐3p upregulation on CRC development and tumor growth. DNMT1 maintained methylation of miR‐152‐3p. TMSB10 was the direct target gene of miR‐152‐3p. Conclusion The study highlights that silenced DNMT1 results in non‐methylated miR‐152‐3p to depress TMSB10 expression, thereby inhibiting CRC development, which provides a new approach for CRC therapy.
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Affiliation(s)
- Chenchen Wang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiaoji Ma
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Jieyun Zhang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiaobin Jia
- Department of General Surgery, Shanghai DF Medical Center, Shanghai, China
| | - Mingzhu Huang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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27
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Casey S, Goasdoue K, Miller SM, Brennan GP, Cowin G, O'Mahony AG, Burke C, Hallberg B, Boylan GB, Sullivan AM, Henshall DC, O'Keeffe GW, Mooney C, Bjorkman T, Murray DM. Temporally Altered miRNA Expression in a Piglet Model of Hypoxic Ischemic Brain Injury. Mol Neurobiol 2020; 57:4322-4344. [PMID: 32720074 PMCID: PMC7383124 DOI: 10.1007/s12035-020-02018-w] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 07/08/2020] [Indexed: 12/21/2022]
Abstract
Hypoxic ischemic encephalopathy (HIE) is the most frequent cause of acquired infant brain injury. Early, clinically relevant biomarkers are required to allow timely application of therapeutic interventions. We previously reported early alterations in several microRNAs (miRNA) in umbilical cord blood at birth in infants with HIE. However, the exact timing of these alterations is unknown. Here, we report serial changes in six circulating, cross-species/bridging biomarkers in a clinically relevant porcine model of neonatal HIE with functional analysis. Six miRNAs—miR-374a, miR-181b, miR-181a, miR-151a, miR-148a and miR-128—were significantly and rapidly upregulated 1-h post-HI. Changes in miR-374a, miR-181b and miR-181a appeared specific to moderate-severe HI. Histopathological injury and five miRNAs displayed positive correlations and were predictive of MRS Lac/Cr ratios. Bioinformatic analysis identified that components of the bone morphogenic protein (BMP) family may be targets of miR-181a. Inhibition of miR-181a increased neurite length in both SH-SY5Y cells at 1 DIV (days in vitro) and in primary cultures of rat neuronal midbrain at 3 DIV. In agreement, inhibition of miR-181a increased expression of BMPR2 in differentiating SH-SY5Y cells. These miRNAs may therefore act as early biomarkers of HIE, thereby allowing for rapid diagnosis and timely therapeutic intervention and may regulate expression of signalling pathways vital to neuronal survival.
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Affiliation(s)
- Sophie Casey
- Irish Centre for Fetal and Neonatal Translational Research (INFANT), University College Cork, Cork, Ireland. .,Department of Paediatrics and Child Health, University College Cork, Cork, Ireland. .,Department of Anatomy and Neuroscience, University College Cork, Room 2.33, Western Gateway Building, Cork, Ireland.
| | - Kate Goasdoue
- Perinatal Research Centre, UQ Centre for Clinical Research, University of Queensland, Brisbane, Australia
| | - Stephanie M Miller
- Perinatal Research Centre, UQ Centre for Clinical Research, University of Queensland, Brisbane, Australia
| | - Gary P Brennan
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Gary Cowin
- National Imaging Facility, Centre for Advanced Imaging, University of Queensland, Brisbane, Australia
| | - Adam G O'Mahony
- Department of Anatomy and Neuroscience, University College Cork, Room 2.33, Western Gateway Building, Cork, Ireland
| | - Christopher Burke
- Department of Pathology, Royal Brisbane and Women's Hospital, Brisbane, Australia
| | - Boubou Hallberg
- Neonatology, Karolinska University Hospital, Stockholm, Sweden
| | - Geraldine B Boylan
- Irish Centre for Fetal and Neonatal Translational Research (INFANT), University College Cork, Cork, Ireland
| | - Aideen M Sullivan
- Department of Anatomy and Neuroscience, University College Cork, Room 2.33, Western Gateway Building, Cork, Ireland
| | - David C Henshall
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.,FutureNeuro Research Centre, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Gerard W O'Keeffe
- Irish Centre for Fetal and Neonatal Translational Research (INFANT), University College Cork, Cork, Ireland.,Department of Anatomy and Neuroscience, University College Cork, Room 2.33, Western Gateway Building, Cork, Ireland
| | - Catherine Mooney
- Irish Centre for Fetal and Neonatal Translational Research (INFANT), University College Cork, Cork, Ireland.,FutureNeuro Research Centre, Royal College of Surgeons in Ireland, Dublin, Ireland.,School of Computer Science, University College Dublin, Dublin, Ireland
| | - Tracey Bjorkman
- Perinatal Research Centre, UQ Centre for Clinical Research, University of Queensland, Brisbane, Australia
| | - Deirdre M Murray
- Irish Centre for Fetal and Neonatal Translational Research (INFANT), University College Cork, Cork, Ireland.,Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
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28
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Chen L, Chen Y, Feng YL, Zhu Y, Wang LQ, Hu S, Cheng P. Tumor circulome in the liquid biopsies for digestive tract cancer diagnosis and prognosis. World J Clin Cases 2020; 8:2066-2080. [PMID: 32548136 PMCID: PMC7281040 DOI: 10.12998/wjcc.v8.i11.2066] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 04/10/2020] [Accepted: 04/28/2020] [Indexed: 02/05/2023] Open
Abstract
Digestive tract cancer is one of the main diseases that endanger human health. At present, the early diagnosis of digestive tract tumors mainly depends on serology, imaging, endoscopy, and so on. Although tissue specimens are the gold standard for cancer diagnosis, with the rapid development of precision medicine in cancer, the demand for dynamic monitoring of tumor molecular characteristics has increased. Liquid biopsy involves the collection of body fluids via non-invasive approaches, and analyzes biological markers such as circulating tumor cells, circulating tumor DNA, circulating cell-free DNA, microRNAs, and exosomes. In recent years, liquid biopsy has become more and more important in the diagnosis and prognosis of cancer in clinical practice due to its convenience, non-invasiveness, high specificity and it overcomes temporal-spatial heterogeneity. Therefore, this review summarizes the current evidence on liquid biopsies in digestive tract cancers in relation to diagnosis and prognosis.
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Affiliation(s)
- Long Chen
- Department of Radiotherapy, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
| | - Yu Chen
- Department of Pediatric Surgery, Guangdong Women and Children Hospital, Guangzhou 511400, Guangdong Province, China
| | - Yuan-Ling Feng
- Department of Obstetrics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310052, Zhejiang Province, China
| | - Yan Zhu
- Department of Respiratory, Shulan Hospital, Hangzhou 310004, Zhejiang Province, China
| | - Li-Quan Wang
- Department of Obstetrics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310052, Zhejiang Province, China
| | - Shen Hu
- Department of Obstetrics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310052, Zhejiang Province, China
| | - Pu Cheng
- Department of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310052, Zhejiang Province, China
- Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou 310052, Zhejiang Province, China
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29
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Yin H, He H, Cao X, Shen X, Han S, Cui C, Zhao J, Wei Y, Chen Y, Xia L, Wang Y, Li D, Zhu Q. MiR-148a-3p Regulates Skeletal Muscle Satellite Cell Differentiation and Apoptosis via the PI3K/AKT Signaling Pathway by Targeting Meox2. Front Genet 2020; 11:512. [PMID: 32582277 PMCID: PMC7287179 DOI: 10.3389/fgene.2020.00512] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 04/27/2020] [Indexed: 12/23/2022] Open
Abstract
As bioinformatic approaches have been developed, it has been demonstrated that microRNAs (miRNAs) are involved in the formation of muscles and play important roles in regulation of muscle cell proliferation and differentiation. Previously, it has been demonstrated that miR-148a-3p is one of the most abundant miRNAs in chicken skeletal muscle. Here, we build on that work and demonstrate that miR-148a-3p is important in the control of differentiation of chicken skeletal muscle satellite cells (SMSCs). Elevated expression of miR-148a-3p significantly promoted differentiation and inhibited apoptosis of SMSCs but did not affect proliferation. Furthermore, it was observed that the mesenchyme homeobox 2 (Meox2) is a target gene of miR-148a-3p and that miR-148a-3p can down-regulate expression of Meox2, which promote differentiation of SMSCs and suppress apoptosis. Furthermore, miR-148a-3p overexpression encouraged activation of the PI3K/AKT signaling pathway, which could be recovered by overexpression of Meox2. Overall, these findings suggest that microRNA-148a-3p is a potent promoter of myogenesis via direct targeting of Meox2 and increase of the PI3K/AKT signaling pathway in chicken SMSCs.
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Affiliation(s)
- Huadong Yin
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Haorong He
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Xinao Cao
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Xiaoxu Shen
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Shunshun Han
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Can Cui
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Jing Zhao
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Yuanhang Wei
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Yuqi Chen
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Lu Xia
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Yan Wang
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Diyan Li
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Qing Zhu
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
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30
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MicroRNA-148a regulates low-density lipoprotein metabolism by repressing the (pro)renin receptor. PLoS One 2020; 15:e0225356. [PMID: 32437440 PMCID: PMC7241754 DOI: 10.1371/journal.pone.0225356] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Accepted: 05/06/2020] [Indexed: 01/15/2023] Open
Abstract
High plasma LDL cholesterol (LDL-c) concentration is a major risk factor for atherosclerosis. Hepatic LDL receptor (LDLR) regulates LDL metabolism, and thereby plasma LDL-c concentration. Recently, we have identified the (pro)renin receptor [(P)RR] as a novel regulator of LDL metabolism, which regulates LDLR degradation and hence its protein abundance and activity. In silico analysis suggests that the (P)RR is a target of miR-148a. In this study we determined whether miR-148a could regulate LDL metabolism by regulating (P)RR expression in HepG2 and Huh7 cells. We found that miR-148a suppressed (P)RR expression by binding to the 3’-untranslated regions (3’-UTR) of the (P)RR mRNA. Mutating the binding sites for miR-148a in the 3’-UTR of (P)RR mRNA completely abolished the inhibitory effects of miR-148a on (P)RR expression. In line with our recent findings, reduced (P)RR expression resulted in decreased cellular LDL uptake, likely as a consequence of decreased LDLR protein abundance. Overexpressing the (P)RR prevented miR-148a-induced reduction in LDLR abundance and cellular LDL uptake. Our study supports a new concept that miR-148a is a regulator of (P)RR expression. By reducing (P)RR abundance, miR-148a decreases LDLR protein abundance and consequently cellular LDL uptake.
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Yin Z, Wang W, Qu G, Wang L, Wang X, Pan Q. MiRNA-96-5p impacts the progression of breast cancer through targeting FOXO3. Thorac Cancer 2020; 11:956-963. [PMID: 32100957 PMCID: PMC7113053 DOI: 10.1111/1759-7714.13348] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 01/21/2020] [Accepted: 01/21/2020] [Indexed: 12/22/2022] Open
Abstract
Background Breast cancer is the most common malignant tumor in women worldwide, with a high mortality rate. MicroRNAs are small non‐coding RNAs that negatively regulate the expression of target genes by interacting with the target gene 3'‐UTR, and participate in cell differentiation, proliferation, apoptosis and metabolism. The function of miRNA‐96‐5p in the progression of breast cancer has not been reported. Methods We used the StarBase database to investigate the expression of miRNA‐96‐5p in breast cancer and adjacent normal tissues. FOXO3 3'‐UTR construct and luciferase reporter assays was performed for the target gene. Expression levels of miRNAs including its target were analyzed by qRT‐PCR and western blot. Cell proliferation was detected by CCK8 and colony formation, EdU assay. Results Luciferase reporter assays showed miRNA‐96‐5p directly targeted FOXO3. Abrogation of miRNA‐96‐5p by transfection with its inhibitors in breast cancer cells significantly suppressed miRNA‐96‐5p expression and breast cancer cells proliferation. Western blot revealed that overexpression of miRNA‐96‐5p substantially reduced FOXO3 protein expression. We used the GEPIA, UALCAN and KM‐plotter databases to investigate the expression of FOXO3 in human breast cancer and adjacent normal tissues, and its correlation with survival. In addition, we found that FOXO3 spoiled miR‐96‐5p induced breast cancer cell proliferation block effecting. Conclusions miRNA‐96‐5p may exert a tumor promotion role through negatively regulating tumor suppressor gene FOXO3 and promoting cell proliferation.
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Affiliation(s)
- Ziyi Yin
- Department of Breast Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Wenyan Wang
- Department of Breast Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Gengbao Qu
- Department of Breast Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Lin Wang
- Department of Breast Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Xiang Wang
- Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou, China
| | - Qin Pan
- Department of Oncology, Liyang People's Hospital, Liyang, China
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Maimaitiming A, Wusiman A, Aimudula A, Kuerban X, Su P. MicroRNA-152 Inhibits Cell Proliferation, Migration, and Invasion in Breast Cancer. Oncol Res 2020; 28:13-19. [PMID: 30982494 PMCID: PMC7851537 DOI: 10.3727/096504019x15519249902838] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
The aim of the present study was to investigate the roles of microRNA-152 (miR-152) in the initiation and progression of breast cancer. The expression level of miR-152 was detected in human breast cancer tissue and a panel of human breast cancer cell lines using qRT-PCR. Results found that miR-152 expression was significantly downregulated in breast cancer tissue samples compared to adjacent noncancerous tissues as well as in breast cancer cell lines. Overexpression of miR-152 significantly suppressed breast cancer cell proliferation, migration, and invasion. Luciferase reporter assay results found that ROCK1 is a direct and functional target gene of miR-152 in breast cancer. In addition, downexpression of ROCK1 could inhibit breast cancer cell proliferation, migration, and invasion. These findings indicate that miR-152 inhibited breast cancer growth and metastasis through negative regulation of ROCK1 expression. These data suggest that miR-152/ROCK1 pathway may be a useful therapeutic target for breast cancer treatment.
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Affiliation(s)
- Adilijiang Maimaitiming
- *Department of Breast and Thyroid Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, P.R. China
| | - Ailijiang Wusiman
- †Department of Surgery, Hospital of Xinjiang Traditional Uyghur, Urumqi, P.R. China
| | - Abulajiang Aimudula
- †Department of Surgery, Hospital of Xinjiang Traditional Uyghur, Urumqi, P.R. China
| | - Xuekelaiti Kuerban
- *Department of Breast and Thyroid Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, P.R. China
| | - Pengcheng Su
- *Department of Breast and Thyroid Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, P.R. China
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Ke M, Zhang Z, Cong L, Zhao S, Li Y, Wang X, Lv Y, Zhu Y, Dong J. MicroRNA-148b-colony-stimulating factor-1 signaling-induced tumor-associated macrophage infiltration promotes hepatocellular carcinoma metastasis. Biomed Pharmacother 2019; 120:109523. [PMID: 31655310 DOI: 10.1016/j.biopha.2019.109523] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 09/24/2019] [Accepted: 10/01/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND MicroRNAs (miRNAs) are small non-coding molecules that exhibit important regulatory roles in various biological or cellular functions, including tumor metastasis. However, the detailed mechanisms of the expression and functions of miRNAs in hepatocellular carcinoma (HCC) have not yet been completely investigated. METHODS In this study, the levels of miR-148b in HCC cells and patient specimens were determined using qPCR assays. MiR-148b-overexpressing HCC cells were used to investigate the effect of miR-148b in vitro and in vivo. The relationship between the expression of miR-148b and colony stimulating factor-1 (CSF1) in HCC patients and the infiltration of macrophages into the tumor microenvironment were assessed by immunohistochemical staining. RESULTS MiR-148b expression was decreased in metastatic HCC cells. A positive association between downregulated miR-148b expression and several clinical parameters, including recurrence, metastasis, and poor prognosis, was observed in patients with HCC. The results of bio-functional experiments indicated that the biological characteristics of HCC cells were not affected by miR-148b deficiency in vitro. However, miR-148b deficiency significantly enhanced the progression and metastasis of HCC in nude mice. By analyzing the gene expression profiles, we demonstrated that CSF1 was regulated by miR-148b and that miR-148b deficiency promoted HCC growth and metastasis through CSF1/CSF1 receptor (CSF1R)-mediated tumor-associated macrophage (TAM) infiltration. These results were supported by the negative relationship between miR-148b and CSF1 expression and TAM infiltration in HCC patients. Moreover, HCC patients with low miR-148b levels and high TAM infiltration were associated with poorer prognosis. CONCLUSION MiR-148b-CSF1 signaling-induced TAM infiltration promotes HCC metastasis. Therefore, miR-148b plays a suppressor role in HCC and might be a potential prognostic factor and therapeutic candidate for HCC.
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Affiliation(s)
- Mengyun Ke
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China; Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China
| | - Zhenhai Zhang
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Longlong Cong
- Department of Vascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China
| | - Shidi Zhao
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China; Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China
| | - Yan Li
- Department of Vascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China
| | - Xiaofei Wang
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Yi Lv
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China; Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China
| | - Ying Zhu
- Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Fudan University, 12 Urumqi Road (M), Shanghai 200040, China.
| | - Jian Dong
- Department of Vascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China; National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China; Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China.
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Feng F, Liu H, Chen A, Xia Q, Zhao Y, Jin X, Huang J. miR-148-3p and miR-152-3p synergistically regulate prostate cancer progression via repressing KLF4. J Cell Biochem 2019; 120:17228-17239. [PMID: 31104329 DOI: 10.1002/jcb.28984] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Revised: 03/23/2019] [Accepted: 04/12/2019] [Indexed: 12/27/2022]
Abstract
BACKGROUND miR-148-3p and miR-152-3p as the tumor suppressors have been reported in various cancer types. Our study is aimed to discuss the synergistic effect of miR-148-3p and miR-152-3p in prostate cancer (PCa). METHODS Bioinformatics algorithm and luciferase reporter assays were used to verify whether miR-148-3p and 152-3p could bind with the 3'-untranslated region (3'-UTR) of Kruppel-like factor 4 (KLF4). PCa cell growth in vivo was analyzed using the mouse xenograft tumor model. RESULTS miR-148-3p and miR-152-3p were reduced in PCa tumor tissues. Moreover, the protein expression of KLF4 was increased in PCa tissues. The 3'-UTR of KLF4 contained the conserved binding sites with miR-148-3p and miR-152-3p. The mimics or inhibitors of miR-148-3p and/or miR-152-3p could downregulated or upregulated KLF4 expression, respectively. miR-148-3p and miR-152-3p-induced PCa cell growth inhibition were observed both in vivo and in vitro. KLF4 overexpression had the ability to neutralize the antitumor effect of miR-148-3p/152-3p in vivo and in vitro. CONCLUSION miR-148-3p/152-3p family could serve as tumor suppressors in PCa via repressing KLF4.
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Affiliation(s)
- Feng Feng
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
- School of Medicine, Shandong University, Jinan, China
| | - Hui Liu
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Aiping Chen
- Liaocheng People's Hospital, Liao Cheng, China
| | - Qinghua Xia
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Yong Zhao
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Xunbo Jin
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Jianjun Huang
- Laboratory of Tumor and Molecular Biology, Academy of Military Medical Sciences, Beijing, China
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Fan Y, Gan M, Tan Y, Chen L, Shen L, Niu L, Liu Y, Tang G, Jiang Y, Li X, Zhang S, Bai L, Zhu L. Mir-152 Regulates 3T3-L1 Preadipocyte Proliferation and Differentiation. Molecules 2019; 24:molecules24183379. [PMID: 31533306 PMCID: PMC6766927 DOI: 10.3390/molecules24183379] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 09/12/2019] [Accepted: 09/16/2019] [Indexed: 01/14/2023] Open
Abstract
Adipogenesis is a complex biological process and the main cause of obesity. Recently, microRNAs (miRNAs), a class of small endogenous non-coding RNAs, have been proven to play an important role in adipogenesis by the post-transcriptional regulation of target genes. In this current study, we observed an increment of miR-152 expression during the process of 3T3-L1 cell audiogenic differentiation. A functional analysis indicated that the overexpression of miR-152 inhibited pre-adipocyte proliferation and suppressed the expression of some cell cycle-related genes. Moreover, the overexpression of miR-152 promoted lipid accumulation in 3T3-L1 preadipocytes accompanied by increase of the expression of some pro-audiogenic genes. Additionally, a dual-luciferase reporter assay demonstrated lipoprotein lipase (LPL) was a direct target gene of miR-152 during preadipocyte differentiation. Further analysis showed that miR-152 was positively correlated with adipogenesis and intramuscular fat formation in vivo. Taken together, our findings suggest that miR-152 could suppress 3T3-L1 preadipocyte proliferation, whereas it could promote 3T3-L1 preadipocyte differentiation by negatively regulating LPL. The findings indicate that miR-152 might have a therapeutic significance for obesity and obesity-related metabolic syndrome.
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Affiliation(s)
- Yuan Fan
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
| | - Mailin Gan
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
| | - Ya Tan
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
- Institute of Animal Husbandry and Veterinary, Guizhou Academy of Agricultural Science, Guiyang 550005, Guizhou, China.
| | - Lei Chen
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
| | - Linyuan Shen
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
| | - Lili Niu
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
| | - Yihui Liu
- Sichuan Province General Station of Animal Husbandry, Chengdu 611130, Sichuan, China.
| | - Guoqing Tang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
| | - Yanzhi Jiang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
| | - Xuewei Li
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
| | - Shunhua Zhang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
| | - Lin Bai
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
| | - Li Zhu
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
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Mironova N, Vlassov V. Surveillance of Tumour Development: The Relationship Between Tumour-Associated RNAs and Ribonucleases. Front Pharmacol 2019; 10:1019. [PMID: 31572192 PMCID: PMC6753386 DOI: 10.3389/fphar.2019.01019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Accepted: 08/09/2019] [Indexed: 12/14/2022] Open
Abstract
Tumour progression is accompanied by rapid cell proliferation, loss of differentiation, the reprogramming of energy metabolism, loss of adhesion, escape of immune surveillance, induction of angiogenesis, and metastasis. Both coding and regulatory RNAs expressed by tumour cells and circulating in the blood are involved in all stages of tumour progression. Among the important tumour-associated RNAs are intracellular coding RNAs that determine the routes of metabolic pathways, cell cycle control, angiogenesis, adhesion, apoptosis and pathways responsible for transformation, and intracellular and extracellular non-coding RNAs involved in regulation of the expression of their proto-oncogenic and oncosuppressing mRNAs. Considering the diversity/variability of biological functions of RNAs, it becomes evident that extracellular RNAs represent important regulators of cell-to-cell communication and intracellular cascades that maintain cell proliferation and differentiation. In connection with the elucidation of such an important role for RNA, a surge in interest in RNA-degrading enzymes has increased. Natural ribonucleases (RNases) participate in various cellular processes including miRNA biogenesis, RNA decay and degradation that has determined their principal role in the sustention of RNA homeostasis in cells. Findings were obtained on the contribution of some endogenous ribonucleases in the maintenance of normal cell RNA homeostasis, which thus prevents cell transformation. These findings directed attention to exogenous ribonucleases as tools to compensate for the malfunction of endogenous ones. Recently a number of proteins with ribonuclease activity were discovered whose intracellular function remains unknown. Thus, the comprehensive investigation of physiological roles of RNases is still required. In this review we focused on the control mechanisms of cell transformation by endogenous ribonucleases, and the possibility of replacing malfunctioning enzymes with exogenous ones.
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Affiliation(s)
- Nadezhda Mironova
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia
| | - Valentin Vlassov
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia
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Curcuminoid Analogs Differentially Modulate Nuclear Factor Kappa-Light-Chain-Enhancer, P65 Serine276, Mitogen- and Stress-activated Protein Kinase 1 And MicroRNA 148a Status. PROGRESS IN PREVENTIVE MEDICINE 2019. [DOI: 10.1097/pp9.0000000000000024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Zhu D, Yuan D, Guo R, Zhang L, Guo T, Zhao Y, Wang J, Chen X, Qian H, Ge H. Overexpression of miR-148a inhibits viability and invasion of ovarian cancer OVCAR3 cells by targeting FOXO3. Oncol Lett 2019; 18:402-410. [PMID: 31289511 PMCID: PMC6539956 DOI: 10.3892/ol.2019.10321] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Accepted: 03/29/2019] [Indexed: 12/31/2022] Open
Abstract
Decreased expression of microRNA (miR)-148a is associated with poor prognosis in ovarian cancer. The aim of the present study was to investigate the impact of miR-148a on tumor cell viability and invasion via targeting forkhead box protein O3 (FOXO3). Expression of miR-148a was detected in paired tumor and adjacent normal tissues. OVCAR3 cells were transfected with miR-148a mimic and inhibitor. Cell viability, apoptosis and invasion were determined. A luciferase reporter assay was used to study the association between miR-148a and FOXO3. In addition, the influence of miR-148a on tumor cell growth was investigated by performing xenograft assays in nude mice. RT-qPCR showed that miR-148a was downregulated in ovarian cancer tissues. Overexpression of miR-148a in OVCAR3 cells inhibited cell viability, suppressed invasion and promoted cellular apoptosis. The dual-luciferase assay indicated that miR-148a directly regulated the expression of FOXO3, a transcription factor of caspase-3. Western blotting confirmed that the expression of caspase-3 was regulated by the modulation of miR-148a expression. In vivo assays revealed that miR-148a overexpression inhibited the growth of OVCAR3 ×enograft tumors in nude mice. miR-148a is a tumor suppressor in ovarian cancer OVCAR3 cells and in nude mice. The suppressive effect is due to inhibiting cell viability and invasion as well as promoting apoptosis. These results may provide theoretical basis for targeting miR-148a in the treatment of ovarian cancer.
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Affiliation(s)
- Dandan Zhu
- Department of Obstetrics and Gynecology, Taizhou People's Hospital, Fifth Affiliated Hospital to Nantong University, Taizhou, Jiangsu 225300, P.R. China
| | - Donglan Yuan
- Department of Obstetrics and Gynecology, Taizhou People's Hospital, Fifth Affiliated Hospital to Nantong University, Taizhou, Jiangsu 225300, P.R. China
| | - Runfa Guo
- Department of Obstetrics and Gynecology, Taizhou People's Hospital, Fifth Affiliated Hospital to Nantong University, Taizhou, Jiangsu 225300, P.R. China
| | - Lixin Zhang
- Department of Obstetrics and Gynecology, Taizhou People's Hospital, Fifth Affiliated Hospital to Nantong University, Taizhou, Jiangsu 225300, P.R. China
| | - Ting Guo
- Central Laboratory, Taizhou People's Hospital, Fifth Affiliated Hospital to Nantong University, Taizhou, Jiangsu 225300, P.R. China
| | - Yinling Zhao
- Department of Obstetrics and Gynecology, Taizhou People's Hospital, Fifth Affiliated Hospital to Nantong University, Taizhou, Jiangsu 225300, P.R. China
| | - Jia Wang
- Department of Obstetrics and Gynecology, Taizhou People's Hospital, Fifth Affiliated Hospital to Nantong University, Taizhou, Jiangsu 225300, P.R. China
| | - Xinping Chen
- Department of Obstetrics and Gynecology, Taizhou People's Hospital, Fifth Affiliated Hospital to Nantong University, Taizhou, Jiangsu 225300, P.R. China
| | - Hua Qian
- Department of Obstetrics and Gynecology, Taizhou People's Hospital, Fifth Affiliated Hospital to Nantong University, Taizhou, Jiangsu 225300, P.R. China
| | - Hongshan Ge
- Department of Obstetrics and Gynecology, Taizhou People's Hospital, Fifth Affiliated Hospital to Nantong University, Taizhou, Jiangsu 225300, P.R. China
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Qin L, Huang J, Wang G, Huang J, Wu X, Li J, Yi W, Qin F, Huang D. Integrated analysis of clinical significance and functional involvement of microRNAs in hepatocellular carcinoma. J Cell Physiol 2019; 234:23581-23595. [PMID: 31210353 DOI: 10.1002/jcp.28927] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 05/21/2019] [Accepted: 05/22/2019] [Indexed: 12/14/2022]
Affiliation(s)
- Li Qin
- Department of Radiation Oncology Liuzhou Worker Hospital Liuzhou Guangxi Province People's Republic of China
| | - Jian Huang
- Department of Radiation Oncology Liuzhou Worker Hospital Liuzhou Guangxi Province People's Republic of China
| | - Guodong Wang
- Department of Radiation Oncology Liuzhou Worker Hospital Liuzhou Guangxi Province People's Republic of China
| | - Jinxin Huang
- Department of Radiation Oncology Liuzhou Worker Hospital Liuzhou Guangxi Province People's Republic of China
| | - Xintian Wu
- Department of Radiation Oncology Liuzhou Worker Hospital Liuzhou Guangxi Province People's Republic of China
| | - Jinzhuan Li
- Department of Radiation Oncology Liuzhou Worker Hospital Liuzhou Guangxi Province People's Republic of China
| | - Weili Yi
- Department of Radiation Oncology Liuzhou Worker Hospital Liuzhou Guangxi Province People's Republic of China
| | - Fuhui Qin
- Department of Radiation Oncology Liuzhou Worker Hospital Liuzhou Guangxi Province People's Republic of China
| | - Dongning Huang
- Department of Radiation Oncology Liuzhou Worker Hospital Liuzhou Guangxi Province People's Republic of China
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Obesity, Insulin Resistance, and Colorectal Cancer: Could miRNA Dysregulation Play A Role? Int J Mol Sci 2019; 20:ijms20122922. [PMID: 31207998 PMCID: PMC6628223 DOI: 10.3390/ijms20122922] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 06/10/2019] [Accepted: 06/13/2019] [Indexed: 12/11/2022] Open
Abstract
Obesity is associated with insulin resistance and low-grade inflammation. Insulin resistance is a risk factor for cancer. A recent chapter in epigenetics is represented by microRNAs (miRNAs), which post-transcriptionally regulate gene expression. Dysregulated miRNA profiles have been associated with diseases including obesity and cancer. Herein we report dysregulated miRNAs in obesity both in animal models and in humans, and we also document dysregulated miRNAs in colorectal cancer (CRC), as example of an obesity-related cancer. Some of the described miRNAs are found to be similarly dysregulated both in obesity, insulin resistance (IR), and CRC. Thus, we present miRNAs as a potential molecular link between obesity and CRC onset and development, giving a new perspective on the role of miRNAs in obesity-associated cancers.
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Ardila HJ, Sanabria-Salas MC, Meneses X, Rios R, Huertas-Salgado A, Serrano ML. Circulating miR-141-3p, miR-143-3p and miR-200c-3p are differentially expressed in colorectal cancer and advanced adenomas. Mol Clin Oncol 2019; 11:201-207. [PMID: 31316774 DOI: 10.3892/mco.2019.1876] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 04/22/2019] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer (CRC) is one of the prominent causes of cancer related deaths because, in part, there is not an early, non-invasive, effective detection strategy. Circulating microRNAs (miRNAs) have been proposed as potential non-invasive biomarkers for CRC. In this study, we evaluated the miRNA profile in sixteen CRC tissues by Next-Generation-Sequencing and compared the circulating expression levels of 22 miRNAs among 45 CRC, 14 hyperplastic polyps, 11 advanced adenoma patients and 45 control subjects, by reverse transcription-quantitative PCR, to search for miRNAs which could be potential biomarkers. In total, nine of them represented 70% of total read counts (miR-10a-5p, miR-192-5p, miR-10b-5p, miR-22-3p, miR-26a-5p, miR-148a-3p, miR-181a-5p, miR-92a-3p and miR-143-5p). In silico analysis found eight candidates to mature miRNAs. With respect to circulating miRNA, we found higher serum expression levels of miR-143-3p, miR-141-3p and miR-200c-3p in the CRC and adenoma groups compared with controls (P<0.002), and we also found significant higher levels of miR-141-3p and miR-200c-3p in serum of adenoma patients compared with the CRC group. In conclusion, the measurement of miRNAs in the blood could complement current screening methods for CRC and might provide new insights into mechanisms of tumorigenesis. miR-143-3p, miR-141-3p and miR-200c-3p could be interesting miRNAs to study as potential biomarkers for CRC.
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Affiliation(s)
- Héctor Javier Ardila
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Bogotá, Colombia.,Instituto de Genética, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia
| | | | - Ximena Meneses
- Unidad de Análisis, Instituto Nacional de Cancerología, Bogotá, Colombia
| | - Rafael Rios
- Unidad de Genética y Resistencia Antimicrobiana, Centro Internacional de Genómica Microbiana, Universidad el Bosque, Bogotá, Colombia
| | | | - Martha Lucía Serrano
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Bogotá, Colombia.,Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia, Bogotá, Colombia
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Up-regulation of miRNA-148a inhibits proliferation, invasion, and migration while promoting apoptosis of cervical cancer cells by down-regulating RRS1. Biosci Rep 2019; 39:BSR20181815. [PMID: 30910849 PMCID: PMC6505193 DOI: 10.1042/bsr20181815] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 03/03/2019] [Accepted: 03/04/2019] [Indexed: 02/07/2023] Open
Abstract
The purpose of the present study is to figure out the role of miRNA-148a (miR-148a) in growth, apoptosis, invasion, and migration of cervical cancer cells by binding to regulator of ribosome synthesis 1 (RRS1). Cervical cancer and adjacent normal tissues, as well as cervical cancer cell line Caski, HeLa, C-33A, and normal cervical epithelial cell line H8 were obtained to detect the expression of miR-148a and RRS1. Relationship between miR-148a and RRS1 expression with clinicopathological characteristics was assessed. The selected Caski and HeLa cells were then transfected with miR-148a mimics, miR-148a inhibitors or RRS1 siRNA to investigate the role of miR-148a and RRS1 on proliferation, apoptosis, colony formation, invasion, and migration abilities of cervical cancer cells. Bioinformatics information and dual luciferase reporter gene assay was for used to detect the targetting relationship between miR-148a and RRS1. Down-regulated miR-148a and up-regulated RRS1 were found in cervical cancer tissues and cells. Down-regulated miR-148a and up-regulated RRS1 are closely related with prognostic factors of cervical cancer. RRS1 was determined as a target gene of miR-148a and miR-148a inhibited RRS1 expression in cervical cancer cells. Up-regulation of miR-148a inhibited cell proliferation, migration, and invasion while promoting apoptosis in Caski and HeLa cells. Our study suggests that miR-148a down-regulates RRS1 expression, thereby inhibiting the proliferation, migration, and invasion while promoting cell apoptosis of cervical cancer cells.
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Moya L, Meijer J, Schubert S, Matin F, Batra J. Assessment of miR-98-5p, miR-152-3p, miR-326 and miR-4289 Expression as Biomarker for Prostate Cancer Diagnosis. Int J Mol Sci 2019; 20:E1154. [PMID: 30845775 PMCID: PMC6429489 DOI: 10.3390/ijms20051154] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Accepted: 02/26/2019] [Indexed: 12/15/2022] Open
Abstract
Prostate cancer (PCa) is one of the most commonly diagnosed cancers worldwide, accounting for almost 1 in 5 new cancer diagnoses in the US alone. The current non-invasive biomarker prostate specific antigen (PSA) has lately been presented with many limitations, such as low specificity and often associated with over-diagnosis. The dysregulation of miRNAs in cancer has been widely reported and it has often been shown to be specific, sensitive and stable, suggesting miRNAs could be a potential specific biomarker for the disease. Previously, we identified four miRNAs that are significantly upregulated in plasma from PCa patients when compared to healthy controls: miR-98-5p, miR-152-3p, miR-326 and miR-4289. This panel showed high specificity and sensitivity in detecting PCa (area under the curve (AUC) = 0.88). To investigate the specificity of these miRNAs as biomarkers for PCa, we undertook an in depth analysis on these miRNAs in cancer from the existing literature and data. Additionally, we explored their prognostic value found in the literature when available. Most studies showed these miRNAs are downregulated in cancer and this is often associated with cancer progression and poorer overall survival rate. These results suggest our four miRNA signatures could potentially become a specific PCa diagnostic tool of which prognostic potential should also be explored.
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Affiliation(s)
- Leire Moya
- Australian Prostate Cancer Research Centre-Queensland, Translational Research Institute, 37 Kent St, Brisbane, Queensland 4102, Australia.
- Cancer Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Brisbane, Queensland 4059, Australia.
| | - Jonelle Meijer
- Australian Prostate Cancer Research Centre-Queensland, Translational Research Institute, 37 Kent St, Brisbane, Queensland 4102, Australia.
- Cancer Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Brisbane, Queensland 4059, Australia.
| | - Sarah Schubert
- Australian Prostate Cancer Research Centre-Queensland, Translational Research Institute, 37 Kent St, Brisbane, Queensland 4102, Australia.
- Cancer Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Brisbane, Queensland 4059, Australia.
| | - Farhana Matin
- Australian Prostate Cancer Research Centre-Queensland, Translational Research Institute, 37 Kent St, Brisbane, Queensland 4102, Australia.
- Cancer Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Brisbane, Queensland 4059, Australia.
| | - Jyotsna Batra
- Australian Prostate Cancer Research Centre-Queensland, Translational Research Institute, 37 Kent St, Brisbane, Queensland 4102, Australia.
- Cancer Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Brisbane, Queensland 4059, Australia.
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Liu J, Ding D, Jiang Z, Du T, Liu J, Kong Z. Long non-coding RNA CCAT1/miR-148a/PKCζ prevents cell migration of prostate cancer by altering macrophage polarization. Prostate 2019; 79:105-112. [PMID: 30221381 DOI: 10.1002/pros.23716] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Accepted: 08/21/2018] [Indexed: 12/31/2022]
Abstract
BACKGROUND Macrophage polarization plays an important role in tumor microenvironment, which regulated the prognosis of prostate cancer. However, the potential role of it is still need further identification. METHODS The M1 Macrophages were inducted using 100 ng/mL LPS and 100 ng/mL IFN-γ, the M1 Macrophages were inducted using 20 ng/mL IL-4. TAMs were obtained by culturing monocytes for 7 days in RPMI 1640 10% FBS with 50% of conditioned medium from PC-3 cells real-time PCR was performed to determine the expression of miR-148a, CCAT1, and PKCζ. Western blot was used to measure the level of PKCζ. The cytokine IL-10 was determined using ELISA. Transwell chamber was carried out to determine cell migration. Luciferase reporter assay was used to determine the relationship between miR-148a and PKCζ. RESULTS The expression of miR-148a was highest in TAMs, while CCAT1 and PKCζ were highest in M1 Macrophages. Overexpressed miR-148a promoted the level of IL-10 and cell migration. Down-regulated CCAT1 promoted the level of IL-10 and cell migration, while this effects were abolished by co-transfection of si-CCAT1 and miR-148a inhibitor. PKCζ is the target gene of miR-148a. The effects of overexpressed miR-148a on the level of IL-10, genes expression, and cell migration were abolished by miR-148a mimic and pcDNA-PKCζ. In vivo experiments verified the effects of CCAT1 and miR-148a on tumor growth. CONCLUSION CCAT1 knockdown promoted M2 macrophages polarization by up-regulating miR-148a, while miR-148a up-regulation promoted M2 macrophages polarization by down-regulating the expression of PKCζ.
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Affiliation(s)
- Jie Liu
- Department of Urology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, P. R. China
| | - Degang Ding
- Department of Urology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, P. R. China
| | - Zhaoqiang Jiang
- Department of Urology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, P. R. China
| | - Tao Du
- Department of Urology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, P. R. China
| | - Jianjun Liu
- Department of Urology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, P. R. China
| | - Zhaohui Kong
- Department of Urology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, P. R. China
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Co-expression profiling of plasma miRNAs and long noncoding RNAs in gastric cancer patients. Gene 2018; 687:135-142. [PMID: 30447342 DOI: 10.1016/j.gene.2018.11.034] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 10/29/2018] [Accepted: 11/13/2018] [Indexed: 12/14/2022]
Abstract
PURPOSE The recent researches indicate that differential non-coding RNAs expression signatures could be associated with the pathogenesis of gastric cancer (GC). However, there are few studies focused on lncRNA-miRNAs co-expression profiling in GC patients. Therefore, in the present study the expression of H19 and MEG3 and their related miRNAs including miR-148a-3p, miR-181a-5p, miR-675-5p and miR-141-3p were determined in the plasma samples of GC patients and controls. MATERIALS AND METHODS This case-control study included 62 GC patients and 40 age- sex matched controls. The non-coding RNA levels were assessed by real-time PCR. Further, using in silico analysis, we identified shared targets of studied miRNAs and performed GC-associated pathway enrichment analysis. RESULTS Our results showed that the H19 level was significantly (P = 0.008) elevated and MEG3 expression was significantly (P = 0.002) down-regulated in GC patients compared to healthy participants. Furthermore, it was revealed that the miR-675-5p level was increased, while miR-141-3p plasma levels were significantly reduced in GC patients (P < 0.05). We did not observe a significant difference for miR-148a-3p (P = 0.682) and miR-181a-5p (P = 0.098) expression between groups. In addition, the expression levels of H19, MEG3 and miR-148a-3p were associated with some clinicopathological features of patients (P < 0.05). ROC analysis revealed that a combination of H19, MEG3 and miR-675-5p levels able to discriminate controls and GC subjects with 88.87% sensitivity and 85% specificity (AUC, 0.927; 0.85-0.96 CI, P < 0.0001). CONCLUSION The results of current study demonstrated that combination of H19, MEG3 and miR-675-5p expression levels could provide a potential diagnostic panel for GC.
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Chen X, Fan Z, McGee W, Chen M, Kong R, Wen P, Xiao T, Chen X, Liu J, Zhu L, Chen R, Wu JY. TDP-43 regulates cancer-associated microRNAs. Protein Cell 2018; 9:848-866. [PMID: 28952053 PMCID: PMC6160384 DOI: 10.1007/s13238-017-0480-9] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Accepted: 08/31/2017] [Indexed: 12/14/2022] Open
Abstract
Aberrant regulation of miRNA genes contributes to pathogenesis of a wide range of human diseases, including cancer. The TAR DNA binding protein 43 (TDP-43), a RNA/DNA binding protein associated with neurodegeneration, is involved in miRNA biogenesis. Here, we systematically examined miRNAs regulated by TDP-43 using RNA-Seq coupled with an siRNA-mediated knockdown approach. TDP-43 knockdown affected the expression of a number of miRNAs. In addition, TDP-43 down-regulation led to alterations in the patterns of different isoforms of miRNAs (isomiRs) and miRNA arm selection, suggesting a previously unknown role of TDP-43 in miRNA processing. A number of TDP-43 associated miRNAs, and their candidate target genes, are associated with human cancers. Our data reveal highly complex roles of TDP-43 in regulating different miRNAs and their target genes. Our results suggest that TDP-43 may promote migration of lung cancer cells by regulating miR-423-3p. In contrast, TDP-43 increases miR-500a-3p expression and binds to the mature miR-500a-3p sequence. Reduced expression of miR-500a-3p is associated with poor survival of lung cancer patients, suggesting that TDP-43 may have a suppressive role in cancer by regulating miR-500a-3p. Cancer-associated genes LIF and PAPPA are possible targets of miR-500a-3p. Our work suggests that TDP-43-regulated miRNAs may play multifaceted roles in the pathogenesis of cancer.
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Affiliation(s)
- Xiaowei Chen
- CAS Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- Guangdong Geneway Decoding Bio-Tech Co. Ltd, Foshan, 528316, China
| | - Zhen Fan
- CAS Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Warren McGee
- Department of Neurology, Center for Genetic Medicine, Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
| | - Mengmeng Chen
- State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- Department of Neurology, Center for Genetic Medicine, Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
| | - Ruirui Kong
- State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Pushuai Wen
- State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Tengfei Xiao
- CAS Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Xiaomin Chen
- CAS Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Jianghong Liu
- State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Li Zhu
- State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Runsheng Chen
- CAS Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
- Research Network of Computational Biology, RNCB, Beijing, 100101, China.
- Guangdong Geneway Decoding Bio-Tech Co. Ltd, Foshan, 528316, China.
| | - Jane Y Wu
- State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
- Department of Neurology, Center for Genetic Medicine, Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
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Fadaka AO, Ojo BA, Adewale OB, Esho T, Pretorius A. Effect of dietary components on miRNA and colorectal carcinogenesis. Cancer Cell Int 2018; 18:130. [PMID: 30202241 PMCID: PMC6127951 DOI: 10.1186/s12935-018-0631-y] [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: 06/22/2018] [Accepted: 08/31/2018] [Indexed: 12/14/2022] Open
Abstract
Background Colorectal cancer (CRC) is one of the most common cancers diagnosed and among the commonest causes of cancer-related mortality globally. Despite the various available treatment options, millions of people still suffer from this illness and most of these treatment options have several limitations. Therefore, a less expensive, non-invasive or a treatment that requires the use of dietary products remains a focal point in this review. Main body Aberrant microRNA expression has been revealed to have a functional role in the initiation and progression of CRC. These has shown significant promise in the diagnosis and prognosis of CRC, owing to their unique expression profile associated with cancer types and malignancies. Moreover, microRNA therapeutics show a great promise in preclinical studies, and these encourage further development of their clinical use in CRC patients. Additionally, emerging studies show the chemo-preventive potential of dietary components in microRNA modulation using several CRC models. This review examines the dietary interplay between microRNAs and CRC incidence. Improving the understanding of the interactions between microRNAs and dietary components in the carcinogenesis of CRC will assist the study of CRC progression and finally, in developing personalized approaches for cancer prevention and therapy. Conclusion Although miRNA research is still at its infancy, it could serve as a promising predictive biomarkers and therapeutic targets for CRC. Given the ever-expanding number of miRNAs, understanding their functional aspects represents a promising option for further research.
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Affiliation(s)
- Adewale Oluwaseun Fadaka
- 1Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape, Cape Town, South Africa.,3Department of Biochemistry, Afe Babalola University, P.M.B. 5454, Ado-Ekiti, Ekiti State Nigeria
| | - Babajide A Ojo
- 2Department of Nutritional Science, Oklahoma State University, 301, Human Sciences, Stillwater, OK 74075 USA
| | - Olusola Bolaji Adewale
- 3Department of Biochemistry, Afe Babalola University, P.M.B. 5454, Ado-Ekiti, Ekiti State Nigeria
| | - Temitope Esho
- 4Institute of Biochemistry II, Medical Faculty, University of Cologne, Joseph-Stelzmann Str. 52, 50931 Cologne, Germany
| | - Ashley Pretorius
- Biotechnology Innovation Division, Aminotek PTY LTD, Suite 2C, Oude Westhof Village Square Bellville, 7530 South Africa
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Ghazanchaei A, Mansoori B, Mohammadi A, Biglari A, Baradaran B. Restoration of miR-152 expression suppresses cell proliferation, survival, and migration through inhibition of AKT-ERK pathway in colorectal cancer. J Cell Physiol 2018; 234:769-776. [PMID: 30076720 DOI: 10.1002/jcp.26891] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2018] [Accepted: 06/12/2018] [Indexed: 01/09/2023]
Abstract
BACKGROUND MiR-152 has been reported as a tumor suppressor microRNA that is downregulated in a number of cancers, including colorectal cancer (CRC). A recent study suggested that miR-152 could be one of the key regulators of CRC. The aim of this study is to investigate the role of miR-152 in CRC and its mechanisms. METHODS The pCMV-GPF-miR-152 vector was transfected into SW-480 and HCT-116 CRC cells via JetPEI transfection reagent. The stable miR-152-expressed cells were selected for the further experiment. To evaluate the effect of miR-152 on cell proliferation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed. Also, the effect of miR-152 on the survival of CRC cells was analyzed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The inhibitory effect of miR-152 on migration was assessed by wound healing scratch assay. Then, the proteins expression levels of protein kinase B (AKT), phosphorylated AKT (p-AKT), extracellular signal-regulated kinase (ERK), and phosphorylated ERK (p-ERK) were measured by the western blot analysis method. RESULTS The result of MTT assay represented miR-152 could inhibit cell proliferation. The TUNEL assay showed miR-152 could induce apoptosis in CRC cells. The wound healing scratch assay showed that miR-152 replacement repressed cell migration in CRC cell lines compared to control groups. The result of protein expression by western blot analysis demonstrated that miR-152 could reduce AKT-p-AKT, and ERK-p-ERK ratio compared to control cells. CONCLUSION Our results show that miR-152 has new anticancer and antimetastatic effect in CRC tissue. The current study showed that miR-152 could be a novel therapeutic small molecule to suppress CRC cell proliferation, survival, and migration by suppressing AKT-ERK signaling pathways.
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Affiliation(s)
- Ardavan Ghazanchaei
- Department of Molecular Medicine and Genetics, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Behzad Mansoori
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Mohammadi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Biglari
- Department of Molecular Medicine and Genetics, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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You W, Zhang X, Ji M, Yu Y, Chen C, Xiong Y, Liu Y, Sun Y, Tan C, Zhang H, Li J, Chen W, Li R. MiR-152-5p as a microRNA passenger strand special functions in human gastric cancer cells. Int J Biol Sci 2018; 14:644-653. [PMID: 29904279 PMCID: PMC6001653 DOI: 10.7150/ijbs.25272] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 03/08/2018] [Indexed: 12/23/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignancies with high mortality rate. MiR-152 may exert the function of tumor suppressor by regulating its target gene, including PIK3CA. Nevertheless, all of the described functions are referred explicitly to miR-152-3p, while miR-152-5p as a passenger strand is poorly realized and entirely ignored. We previously selected miR-152-5p as a candidate using cell migration inhibition screening for GC cells and predicted that miR-152-5p might also target PIK3CA. In this study, we found an abnormal proportion of miR-152-3p / miR-152-5p in GC (gastric cancer) tissues and cells and demonstrated that miR-152-5p had poorer stability in GC cells, revealing the possibility that miR-152-5p is abnormally "suppressed" in gastric cancer. We also investigated and confirmed the role of miR-152-5p in GC by a series of experiments, and found that miR-152-5p modulated cell viability, migration, invasion, and cell-cycle progression of human GC cells, and also inhibited tumor growth and metastasis in vivo partially by targeting PIK3CA. More interestingly, it was proved that miR-152-3p and miR-152-5p had synergistic effects on the inhibition of PIK3CA in GC cells. The results of this study suggest that miR-152-5p may act as a tumor suppressor in SGC-7901 gastric cancer cells via targeting PIK3CA. Further, the study provides a novel insight into the roles of miRNA* during carcinogenesis.
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Affiliation(s)
- Wendao You
- Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Xing Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Mengyue Ji
- Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Yang Yu
- Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Chen Chen
- Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Yujia Xiong
- Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Yiting Liu
- Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Yibin Sun
- Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Chenhuan Tan
- Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | | | - Jie Li
- Genex Health Co., Ltd, Beijing, China
| | - Weichang Chen
- Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Rui Li
- Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
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Sengupta D, Deb M, Patra SK. Antagonistic activities of miR-148a and DNMT1: Ectopic expression of miR-148a impairs DNMT1 mRNA and dwindle cell proliferation and survival. Gene 2018; 660:68-79. [PMID: 29596883 DOI: 10.1016/j.gene.2018.03.075] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 02/21/2018] [Accepted: 03/22/2018] [Indexed: 12/20/2022]
Abstract
Functional analyses of noncoding RNAs have associated many micro RNAs (miRNA, miR) with various physiological processes, including proliferation, differentiation, development, cell metabolism, and apoptosis. Aberrant expression of miRNA and imbalance in their functions may lead to cellular aberration and different disease development, including cancer. In silico analysis of miRNA target prediction suggested that miR-148a possess a binding site in the 3' UTR of DNMT1 mRNA which can cause silencing of DNMT1 gene. Accordingly, we performed in vitro cell culture experiments to confirm the effect miR-148a on DNMT1 gene expression in prostate cancer cell lines. We demonstrated that there is a physical association between DNMT1 mRNA and miR-148a. We found that (i) ectopic expression of miR-148a induces programmed cell death and represses cell proliferation by targeting DNMT1; (ii) miR-148a gene is regulated by DNA methylation and DNMT1 in prostate cancer. We conclude that miR-148a is silenced by DNA methylation and ectopic expression of miR-148a suppresses DNMT1 expression and induced apoptotic genes expression in hormone-refractory prostate cancer cells.
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Affiliation(s)
- Dipta Sengupta
- Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008, India
| | - Moonmoon Deb
- Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008, India
| | - Samir Kumar Patra
- Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008, India.
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