{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:03:53Z","timestamp":1790813033509,"version":"4.1.0"},"reference-count":38,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Research and development fund project of Dongguan People's Hospital."}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Technol Cancer Res Treat"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Background: Cancer resistance to chemotherapy is closely associated with changes in transporter systems. In this study, we investigated the possible regulation of 1 copper ion transporter (ATP7A; ATPase copper transporting alpha) by microRNA miR-495 and its implications in cisplatin resistance and angiogenesis in esophageal cancer. Methods: MiR-495 and ATP7A mRNA expression in clinical tissue samples and 2 cancer cell lines (Eca-109 and TE1) were detected by quantitative real-time polymerase chain reaction. The levels of miR-495 and ATP7A expression in Eca-109 and TE1 cells were increased by transfection with miR-495 mimics and ATP7A-overexpression vectors. Cell proliferation, apoptosis, and angiogenesis were assessed by CCK-8, flow cytometry, and tube formation assays, respectively. The levels of TNF-\u03b1 and VEGF in cell culture supernatants were detected by enzyme linked immunosorbent assay, and in situ expression of NLRP3 was measured by immunofluorescence. The binding of miR-495 to ATP7A sequences was verified by dual luciferase reporter assays. Results:ATP7A expression was significantly increased, while miR-495 expression was decreased in the cancer tissues of esophageal cancer patients. MiR-495 mimics decreased the proliferation and promoted the apoptosis of cisplatin-resistant Eca-109 and TE1 cells. Furthermore, tube formation by human umbilical vein endothelial cells, TNF-\u03b1 and VEGF secretion, and the levels of MRP1, ABCG1, ABCA1, and NLRP3 expression in cisplatin-resistant Eca-109 and TE1 cells were all reduced by miR-495 mimics. MiR-495 was shown to directly bind to ATP7A gene sequences to repress ATP7A expression in Eca-109 and TE1 cells. ATP7A overexpression substantially abrogated the changes in proliferation, apoptosis, angiogenesis, and above-mentioned gene expression in cisplatin-resistant Eca-109 and TE1 cells. Conclusions: MiR-495 suppressed cisplatin resistance and angiogenesis in esophageal cancer cells by targeting ATP7A gene expression.<\/jats:p>","DOI":"10.1177\/15330338211039127","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T08:47:05Z","timestamp":1636361225000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":29,"title":["MiR-495 Inhibits Cisplatin Resistance and Angiogenesis in Esophageal Cancer by Targeting ATP7A"],"prefix":"10.1177","volume":"20","author":[{"given":"Zhuanghua","family":"Li","sequence":"first","affiliation":[{"name":"Affiliated Dongguan People\u2019s Hospital, Southern Medical University, Dongguan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaowen","family":"Li","sequence":"additional","affiliation":[{"name":"Shenzhen People\u2019s Hospital, Shenzhen, 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