Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice
Mus spretus mice are highly resistant to several types of cancer compared to Mus musculus mice. To determine whether differences in microRNA (miRNA) expression account for some of the differences in observed skin cancer susceptibility between the strains, we performed miRNA expression profiling of s...
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| Format: | Article |
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PeerJ Inc.
2013-04-01
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| Online Access: | https://peerj.com/articles/68.pdf |
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| author | Jessica L. Fleming Dustin L. Gable Somayeh Samadzadeh-Tarighat Luke Cheng Lianbo Yu Jessica L. Gillespie Amanda Ewart Toland |
| author_facet | Jessica L. Fleming Dustin L. Gable Somayeh Samadzadeh-Tarighat Luke Cheng Lianbo Yu Jessica L. Gillespie Amanda Ewart Toland |
| author_sort | Jessica L. Fleming |
| collection | DOAJ |
| description | Mus spretus mice are highly resistant to several types of cancer compared to Mus musculus mice. To determine whether differences in microRNA (miRNA) expression account for some of the differences in observed skin cancer susceptibility between the strains, we performed miRNA expression profiling of skin RNA for over 300 miRNAs. Five miRNAs, miR-1, miR-124a-3, miR-133a, miR-134, miR-206, were differentially expressed by array and/or qPCR. miR-1 was previously shown to have tumor suppressing abilities in multiple tumor types. We found miR-1 expression to be lower in mouse cutaneous squamous cell carcinomas (cSCCs) compared to normal skin. Based on the literature and our expression data, we performed detailed studies on predicted miR-1 targets and evaluated the effect of miR-1 expression on two murine cSCC cell lines, A5 and B9. Following transfection of miR-1, we found decreased mRNA expression of three validated miR-1 targets, Met, Twf1 and Ets1 and one novel target Bag4. Decreased expression of Ets1 was confirmed by Western analysis and by 3’ reporter luciferase assays containing wildtype and mutated Ets1 3’UTR. We evaluated the effect of miR-1 on multiple tumor phenotypes including apoptosis, proliferation, cell cycle and migration. In A5 cells, expression of miR-1 led to decreased proliferation compared to a control miR. miR-1 expression also led to increased apoptosis at later time points (72 and 96 h) and to a decrease in cells in S-phase. In summary, we identified five miRNAs with differential expression between cancer resistant and cancer susceptible mice and found that miR-1, a candidate tumor suppressor, has targets with defined roles in tumorigenesis. |
| first_indexed | 2024-03-09T07:27:38Z |
| format | Article |
| id | doaj.art-cb22ece126a7415a816c33254e730675 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T07:27:38Z |
| publishDate | 2013-04-01 |
| publisher | PeerJ Inc. |
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| series | PeerJ |
| spelling | doaj.art-cb22ece126a7415a816c33254e7306752023-12-03T06:52:09ZengPeerJ Inc.PeerJ2167-83592013-04-011e6810.7717/peerj.6868Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible miceJessica L. Fleming0Dustin L. Gable1Somayeh Samadzadeh-Tarighat2Luke Cheng3Lianbo Yu4Jessica L. Gillespie5Amanda Ewart Toland6Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USABiomedical Science Program, The Ohio State University, Columbus, OH, USADivision of Hematology/Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USABiomedical Science Program, The Ohio State University, Columbus, OH, USAThe Center for Biostatistics, The Ohio State University, Columbus, OH, USADepartment of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USADepartment of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USAMus spretus mice are highly resistant to several types of cancer compared to Mus musculus mice. To determine whether differences in microRNA (miRNA) expression account for some of the differences in observed skin cancer susceptibility between the strains, we performed miRNA expression profiling of skin RNA for over 300 miRNAs. Five miRNAs, miR-1, miR-124a-3, miR-133a, miR-134, miR-206, were differentially expressed by array and/or qPCR. miR-1 was previously shown to have tumor suppressing abilities in multiple tumor types. We found miR-1 expression to be lower in mouse cutaneous squamous cell carcinomas (cSCCs) compared to normal skin. Based on the literature and our expression data, we performed detailed studies on predicted miR-1 targets and evaluated the effect of miR-1 expression on two murine cSCC cell lines, A5 and B9. Following transfection of miR-1, we found decreased mRNA expression of three validated miR-1 targets, Met, Twf1 and Ets1 and one novel target Bag4. Decreased expression of Ets1 was confirmed by Western analysis and by 3’ reporter luciferase assays containing wildtype and mutated Ets1 3’UTR. We evaluated the effect of miR-1 on multiple tumor phenotypes including apoptosis, proliferation, cell cycle and migration. In A5 cells, expression of miR-1 led to decreased proliferation compared to a control miR. miR-1 expression also led to increased apoptosis at later time points (72 and 96 h) and to a decrease in cells in S-phase. In summary, we identified five miRNAs with differential expression between cancer resistant and cancer susceptible mice and found that miR-1, a candidate tumor suppressor, has targets with defined roles in tumorigenesis.https://peerj.com/articles/68.pdfmicroRNASkin cancermiR-1 |
| spellingShingle | Jessica L. Fleming Dustin L. Gable Somayeh Samadzadeh-Tarighat Luke Cheng Lianbo Yu Jessica L. Gillespie Amanda Ewart Toland Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice PeerJ microRNA Skin cancer miR-1 |
| title | Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice |
| title_full | Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice |
| title_fullStr | Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice |
| title_full_unstemmed | Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice |
| title_short | Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice |
| title_sort | differential expression of mir 1 a putative tumor suppressing microrna in cancer resistant and cancer susceptible mice |
| topic | microRNA Skin cancer miR-1 |
| url | https://peerj.com/articles/68.pdf |
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