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- Publisher Website: 10.1371/journal.pone.0139489
- Scopus: eid_2-s2.0-84947976484
- PMID: 26418018
- WOS: WOS:000362171400093
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Article: Lysophosphatidic acid mediates activating transcription factor 3 expression which is a target for post-transcriptional silencing by miR-30c-2-3p
Title | Lysophosphatidic acid mediates activating transcription factor 3 expression which is a target for post-transcriptional silencing by miR-30c-2-3p |
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Authors | |
Issue Date | 2015 |
Citation | PLoS ONE, 2015, v. 10, n. 9, article no. e0139489 How to Cite? |
Abstract | Although microRNAs (miRNAs) are small, non-protein-coding entities, they have important roles in post-transcriptional regulation of most of the human genome. These small entities generate fine-tuning adjustments in the expression of mRNA, which can mildly or massively affect the abundance of proteins. Previously, we found that the expression of miR-30c-2-3p is induced by lysophosphatidic acid and has an important role in the regulation of cell proliferation in ovarian cancer cells. The goal here is to confirm that ATF3 mRNA is a target of miR-30c-2-3p silencing, thereby further establishing the functional role of miR-30c-2-3p. Using a combination of bioinformatics, qRT-PCR, immunoblotting and luciferase assays, we uncovered a regulatory pathway between miR-30c-2-3p and the expression of the transcription factor, ATF3. Lysophosphatidic acids triggers the expression of both miR-30c-2-3p and ATF3, which peak at 1 h and are absent 8 h post stimulation in SKOV-3 and OVCAR-3 serous ovarian cancer cells. The 3′-untranslated region (3′-UTR) of ATF3 was a predicted, putative target for miR-30c-2-3p, which we confirmed as a bona-fide interaction using a luciferase reporter assay. Specific mutations introduced into the predicted site of interaction between miR-30c-2-3p and the 3′-UTR of ATF3 alleviated the suppression of the luciferase signal. Furthermore, the presence of anti-miR-30c-2-3p enhanced ATF3 mRNA and protein after lysophosphatidic acid stimulation. Thus, the data suggest that after the expression of ATF3 and miR-30c-2-3p are elicited by lysophosphatidic acid, subsequently miR-30c-2-3p negatively regulates the expression of ATF3 through post-transcriptional silencing, which prevents further ATF3-related outcomes as a consequence of lysophosphatidic acid signaling. |
Persistent Identifier | http://hdl.handle.net/10722/342502 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Nguyen, Ha T. | - |
dc.contributor.author | Jia, Wei | - |
dc.contributor.author | Beedle, Aaron M. | - |
dc.contributor.author | Kennedy, Eileen J. | - |
dc.contributor.author | Murph, Mandi M. | - |
dc.date.accessioned | 2024-04-17T07:04:16Z | - |
dc.date.available | 2024-04-17T07:04:16Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | PLoS ONE, 2015, v. 10, n. 9, article no. e0139489 | - |
dc.identifier.uri | http://hdl.handle.net/10722/342502 | - |
dc.description.abstract | Although microRNAs (miRNAs) are small, non-protein-coding entities, they have important roles in post-transcriptional regulation of most of the human genome. These small entities generate fine-tuning adjustments in the expression of mRNA, which can mildly or massively affect the abundance of proteins. Previously, we found that the expression of miR-30c-2-3p is induced by lysophosphatidic acid and has an important role in the regulation of cell proliferation in ovarian cancer cells. The goal here is to confirm that ATF3 mRNA is a target of miR-30c-2-3p silencing, thereby further establishing the functional role of miR-30c-2-3p. Using a combination of bioinformatics, qRT-PCR, immunoblotting and luciferase assays, we uncovered a regulatory pathway between miR-30c-2-3p and the expression of the transcription factor, ATF3. Lysophosphatidic acids triggers the expression of both miR-30c-2-3p and ATF3, which peak at 1 h and are absent 8 h post stimulation in SKOV-3 and OVCAR-3 serous ovarian cancer cells. The 3′-untranslated region (3′-UTR) of ATF3 was a predicted, putative target for miR-30c-2-3p, which we confirmed as a bona-fide interaction using a luciferase reporter assay. Specific mutations introduced into the predicted site of interaction between miR-30c-2-3p and the 3′-UTR of ATF3 alleviated the suppression of the luciferase signal. Furthermore, the presence of anti-miR-30c-2-3p enhanced ATF3 mRNA and protein after lysophosphatidic acid stimulation. Thus, the data suggest that after the expression of ATF3 and miR-30c-2-3p are elicited by lysophosphatidic acid, subsequently miR-30c-2-3p negatively regulates the expression of ATF3 through post-transcriptional silencing, which prevents further ATF3-related outcomes as a consequence of lysophosphatidic acid signaling. | - |
dc.language | eng | - |
dc.relation.ispartof | PLoS ONE | - |
dc.title | Lysophosphatidic acid mediates activating transcription factor 3 expression which is a target for post-transcriptional silencing by miR-30c-2-3p | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1371/journal.pone.0139489 | - |
dc.identifier.pmid | 26418018 | - |
dc.identifier.scopus | eid_2-s2.0-84947976484 | - |
dc.identifier.volume | 10 | - |
dc.identifier.issue | 9 | - |
dc.identifier.spage | article no. e0139489 | - |
dc.identifier.epage | article no. e0139489 | - |
dc.identifier.eissn | 1932-6203 | - |
dc.identifier.isi | WOS:000362171400093 | - |