{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:31:10Z","timestamp":1791599470411,"version":"4.3.4"},"reference-count":0,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T00:00:00Z","timestamp":1570665600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-sa\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Pharm Pharm Sci"],"abstract":"<jats:p>PURPOSE. Several anticancer drugs including bleomycin (BLM) and methotrexate (MTX) cause serious lung diseases such as pulmonary fibrosis. Although evidences showing the association of epithelial-mesenchymal transition (EMT) with pulmonary fibrosis are increasing, the mechanism underlying anticancer drug-induced EMT has been poorly understood. On the other hand, miR-34a, a non-coding small RNA, has been highlighted as a key factor to regulate EMT in lung. In this study, we elucidated the role of miR-34a in anticancer drug-induced EMT using A549\/ABCA3 cells as a novel type II alveolar epithelium model. METHODS. Expression levels of \u03b1-smooth muscle actin (\u03b1-SMA) mRNA, miR-34a, and p53 were evaluated by real-time PCR and western blot analysis, respectively. RESULTS. BLM and MTX induced EMT-like morphological changes and increase in mRNA expression level of \u03b1-SMA, an EMT marker. Also, both drugs increased the expression level of miR-34a. Furthermore, mRNA expression level of \u03b1-SMA was enhanced by introduction of miR-34a mimic into A549\/ABCA3 cells. To examine the mechanism underlying drug-induced enhancement of miR-34a expression, we focused on p53\/miR-34a axis. Both drugs upregulated protein expression of p53, an inducer of miR-34a, as well as phosphorylation of Ser15 in p53. CONCLUSIONS. These findings indicated that p53\/miR-34a axis may contribute to anticancer drug-induced EMT in type II alveolar epithelial cells.<\/jats:p>","DOI":"10.18433\/jpps30660","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T04:51:27Z","timestamp":1570769487000},"page":"516-524","source":"Crossref","is-referenced-by-count":17,"title":["Anticancer Drug-Induced Epithelial-Mesenchymal Transition via p53\/miR-34a axis in A549\/ABCA3 Cells"],"prefix":"10.3389","volume":"22","author":[{"given":"Ayano","family":"Yamamoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2162-6769","authenticated-orcid":false,"given":"Masashi","family":"Kawami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Konaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinnosuke","family":"Takenaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Yumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2865-3129","authenticated-orcid":false,"given":"Mikihisa","family":"Takano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,10,10]]},"container-title":["Journal of Pharmacy &amp; Pharmaceutical Sciences"],"original-title":[],"link":[{"URL":"https:\/\/journals.library.ualberta.ca\/jpps\/index.php\/JPPS\/article\/download\/30660\/21535","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.library.ualberta.ca\/jpps\/index.php\/JPPS\/article\/download\/30660\/21535","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T13:35:51Z","timestamp":1673616951000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.library.ualberta.ca\/jpps\/index.php\/JPPS\/article\/view\/30660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,10]]},"references-count":0,"URL":"https:\/\/doi.org\/10.18433\/jpps30660","relation":{},"ISSN":["1482-1826","1482-1826"],"issn-type":[{"value":"1482-1826","type":"electronic"},{"value":"1482-1826","type":"print"}],"subject":[],"published":{"date-parts":[[2019,10,10]]}}}