miR-143 and miR-145 disrupt the cervical epithelial barrier through dysregulation of cell adhesion, apoptosis and proliferation
Abstract Molecular mechanisms regulating preterm birth (PTB)-associated cervical remodeling remain unclear. Prior work demonstrated an altered miRNA profile, with significant increases in miR-143 and miR-145, in cervical cells of women destined to have a PTB. The study objective was to determine the...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-03217-7 |
| _version_ | 1818835131326005248 |
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| author | Lauren Anton Ann DeVine Luz-Jeannette Sierra Amy G. Brown Michal A. Elovitz |
| author_facet | Lauren Anton Ann DeVine Luz-Jeannette Sierra Amy G. Brown Michal A. Elovitz |
| author_sort | Lauren Anton |
| collection | DOAJ |
| description | Abstract Molecular mechanisms regulating preterm birth (PTB)-associated cervical remodeling remain unclear. Prior work demonstrated an altered miRNA profile, with significant increases in miR-143 and miR-145, in cervical cells of women destined to have a PTB. The study objective was to determine the effect of miR-143 and miR-145 on the cervical epithelial barrier and to elucidate the mechanisms by which these miRNAs modify cervical epithelial cell function. Ectocervical and endocervical cells transfected with miR-negative control, miR-143 or miR-145 were used in cell permeability and flow cytometry assays for apoptosis and proliferation. miR-143 and miR-145 target genes associated with cell adhesion, apoptosis and proliferation were measured. Epithelial cell permeability was increased in miR-143 and miR-145 transfected cervical epithelial cells. Cell adhesion genes, JAM-A and FSCN1, were downregulated with overexpression of miR-143 and miR-145. miR-143 and miR-145 transfection decreased cervical cell number by increasing apoptosis and decreasing cell proliferation through initiation of cell cycle arrest. Apoptosis genes, BCL2 and BIRC5, and proliferation genes, CDK1 and CCND2, were repressed by miR-143 and miR-145. These findings suggest that miR-143 and miR-145 play a significant role in cervical epithelial barrier breakdown through diverse mechanisms and could contribute to premature cervical remodeling associated with PTB. |
| first_indexed | 2024-12-19T02:45:50Z |
| format | Article |
| id | doaj.art-410b76c60e4346da82360675beedfa9b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T02:45:50Z |
| publishDate | 2017-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-410b76c60e4346da82360675beedfa9b2022-12-21T20:38:52ZengNature PortfolioScientific Reports2045-23222017-06-017111510.1038/s41598-017-03217-7miR-143 and miR-145 disrupt the cervical epithelial barrier through dysregulation of cell adhesion, apoptosis and proliferationLauren Anton0Ann DeVine1Luz-Jeannette Sierra2Amy G. Brown3Michal A. Elovitz4Maternal and Child Health Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine at the University of PennsylvaniaMaternal and Child Health Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine at the University of PennsylvaniaMaternal and Child Health Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine at the University of PennsylvaniaMaternal and Child Health Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine at the University of PennsylvaniaMaternal and Child Health Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine at the University of PennsylvaniaAbstract Molecular mechanisms regulating preterm birth (PTB)-associated cervical remodeling remain unclear. Prior work demonstrated an altered miRNA profile, with significant increases in miR-143 and miR-145, in cervical cells of women destined to have a PTB. The study objective was to determine the effect of miR-143 and miR-145 on the cervical epithelial barrier and to elucidate the mechanisms by which these miRNAs modify cervical epithelial cell function. Ectocervical and endocervical cells transfected with miR-negative control, miR-143 or miR-145 were used in cell permeability and flow cytometry assays for apoptosis and proliferation. miR-143 and miR-145 target genes associated with cell adhesion, apoptosis and proliferation were measured. Epithelial cell permeability was increased in miR-143 and miR-145 transfected cervical epithelial cells. Cell adhesion genes, JAM-A and FSCN1, were downregulated with overexpression of miR-143 and miR-145. miR-143 and miR-145 transfection decreased cervical cell number by increasing apoptosis and decreasing cell proliferation through initiation of cell cycle arrest. Apoptosis genes, BCL2 and BIRC5, and proliferation genes, CDK1 and CCND2, were repressed by miR-143 and miR-145. These findings suggest that miR-143 and miR-145 play a significant role in cervical epithelial barrier breakdown through diverse mechanisms and could contribute to premature cervical remodeling associated with PTB.https://doi.org/10.1038/s41598-017-03217-7 |
| spellingShingle | Lauren Anton Ann DeVine Luz-Jeannette Sierra Amy G. Brown Michal A. Elovitz miR-143 and miR-145 disrupt the cervical epithelial barrier through dysregulation of cell adhesion, apoptosis and proliferation Scientific Reports |
| title | miR-143 and miR-145 disrupt the cervical epithelial barrier through dysregulation of cell adhesion, apoptosis and proliferation |
| title_full | miR-143 and miR-145 disrupt the cervical epithelial barrier through dysregulation of cell adhesion, apoptosis and proliferation |
| title_fullStr | miR-143 and miR-145 disrupt the cervical epithelial barrier through dysregulation of cell adhesion, apoptosis and proliferation |
| title_full_unstemmed | miR-143 and miR-145 disrupt the cervical epithelial barrier through dysregulation of cell adhesion, apoptosis and proliferation |
| title_short | miR-143 and miR-145 disrupt the cervical epithelial barrier through dysregulation of cell adhesion, apoptosis and proliferation |
| title_sort | mir 143 and mir 145 disrupt the cervical epithelial barrier through dysregulation of cell adhesion apoptosis and proliferation |
| url | https://doi.org/10.1038/s41598-017-03217-7 |
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