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- Publisher Website: 10.1016/j.canlet.2018.05.037
- Scopus: eid_2-s2.0-85048318401
- PMID: 29859298
- WOS: WOS:000440118300009
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Article: Autotaxin exacerbates tumor progression by enhancing MEK1 and overriding the function of miR-489-3p
Title | Autotaxin exacerbates tumor progression by enhancing MEK1 and overriding the function of miR-489-3p |
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Authors | |
Keywords | Cancer Lysophosphatidic acid MAPK miRNA Serum biomarkers |
Issue Date | 2018 |
Citation | Cancer Letters, 2018, v. 432, p. 84-92 How to Cite? |
Abstract | Upregulated expression of autotaxin, a secreted phospholipase and phosphodiesterase enzyme, appears in malignant disease. The identification of a circulating miRNA signature should distinguish autotaxin-mediated disease and also elucidate unknown molecular mechanisms that rationalize its malignant potential. Using female transgenic ‘AT-ATX’ mice, whereby human wild-type autotaxin is expressed in liver under the control of the alpha-1 antitrypsin promoter, transgenic animals express augmented autotaxin in circulation and a percentage develop tumors. Serum collected at necropsy had circulating miRNAs analyzed for statistical significance. The ensuing autotaxin-mediated miRNome differentiated between groups: healthy FVB/N mice versus AT-ATX mice with and without tumors. Intriguingly, miR-489-3p was sharply increased in AT-ATX tumor-bearing mice. Tissue analysis showed a correlation between miR-489-3p expression in tumors and surrounding milieu with autotaxin concentration in circulation. Sequence alignment suggested miR-489-3p targets MEK1, which was confirmed through in vitro studies. Exogenously added miR-489-3p, which decreases MEK1 in normal cells, dramatically increased MEK1 expression in cells stably expressing autotaxin. Taken together, this suggests that autotaxin overrides the normal regulatory function of miR-489-3p to inhibit MEK1 via coordinately increased miR-489-3p appearing in serum. |
Persistent Identifier | http://hdl.handle.net/10722/342568 |
ISSN | 2023 Impact Factor: 9.1 2023 SCImago Journal Rankings: 2.595 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Kuppa, Sudeepti S. | - |
dc.contributor.author | Jia, Wei | - |
dc.contributor.author | Liu, Shuying | - |
dc.contributor.author | Nguyen, Ha | - |
dc.contributor.author | Smyth, Susan S. | - |
dc.contributor.author | Mills, Gordon B. | - |
dc.contributor.author | Dobbin, Kevin K. | - |
dc.contributor.author | Hardman, William J. | - |
dc.contributor.author | Murph, Mandi M. | - |
dc.date.accessioned | 2024-04-17T07:04:43Z | - |
dc.date.available | 2024-04-17T07:04:43Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Cancer Letters, 2018, v. 432, p. 84-92 | - |
dc.identifier.issn | 0304-3835 | - |
dc.identifier.uri | http://hdl.handle.net/10722/342568 | - |
dc.description.abstract | Upregulated expression of autotaxin, a secreted phospholipase and phosphodiesterase enzyme, appears in malignant disease. The identification of a circulating miRNA signature should distinguish autotaxin-mediated disease and also elucidate unknown molecular mechanisms that rationalize its malignant potential. Using female transgenic ‘AT-ATX’ mice, whereby human wild-type autotaxin is expressed in liver under the control of the alpha-1 antitrypsin promoter, transgenic animals express augmented autotaxin in circulation and a percentage develop tumors. Serum collected at necropsy had circulating miRNAs analyzed for statistical significance. The ensuing autotaxin-mediated miRNome differentiated between groups: healthy FVB/N mice versus AT-ATX mice with and without tumors. Intriguingly, miR-489-3p was sharply increased in AT-ATX tumor-bearing mice. Tissue analysis showed a correlation between miR-489-3p expression in tumors and surrounding milieu with autotaxin concentration in circulation. Sequence alignment suggested miR-489-3p targets MEK1, which was confirmed through in vitro studies. Exogenously added miR-489-3p, which decreases MEK1 in normal cells, dramatically increased MEK1 expression in cells stably expressing autotaxin. Taken together, this suggests that autotaxin overrides the normal regulatory function of miR-489-3p to inhibit MEK1 via coordinately increased miR-489-3p appearing in serum. | - |
dc.language | eng | - |
dc.relation.ispartof | Cancer Letters | - |
dc.subject | Cancer | - |
dc.subject | Lysophosphatidic acid | - |
dc.subject | MAPK | - |
dc.subject | miRNA | - |
dc.subject | Serum biomarkers | - |
dc.title | Autotaxin exacerbates tumor progression by enhancing MEK1 and overriding the function of miR-489-3p | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.canlet.2018.05.037 | - |
dc.identifier.pmid | 29859298 | - |
dc.identifier.scopus | eid_2-s2.0-85048318401 | - |
dc.identifier.volume | 432 | - |
dc.identifier.spage | 84 | - |
dc.identifier.epage | 92 | - |
dc.identifier.eissn | 1872-7980 | - |
dc.identifier.isi | WOS:000440118300009 | - |