MiR-218-5p/EGFR Signaling in Arsenic-Induced Carcinogenesis.
MiR-218-5p/EGFR Signaling in Arsenic-Induced Carcinogenesis.
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EGFR上调在肺癌中起重要作用，是肺癌治疗的公认靶点。然而，由于慢性砷暴露，EGFR上调的作用和机制仍有待阐明。在这里，我们证明了miR-218- 5 p在砷诱导的转化（As-T）细胞中显著下调。它作为一种肿瘤抑制因子，通过直接靶向EGFR抑制细胞增殖、迁移、集落形成和管形成，并抑制肿瘤生长和血管生成。我们的研究结果表明，218- 5 p/EGFR信号通路可能是一个潜在的治疗慢性砷暴露诱发的肺癌的治疗靶点。背景：砷是一种众所周知的致癌物质，可诱发肺癌、皮肤癌、膀胱癌和肝癌。表皮生长因子受体（EGFR）的异常表达在肺癌中很常见，它参与了癌症的发生、发展、转移和治疗抵抗。然而，砷诱导EGFR上调的潜在机制仍不清楚。方法：采用RT-PCR和免疫印迹法检测miR-218- 5 p和EGFR的表达水平。荧光素酶法检测miR-218- 5 p介导的EGFR转录活性。使用细胞增殖、集落形成、伤口愈合、迁移测定、管形成测定和肿瘤生长测定来研究miR-218- 5 p/EGFR信号传导的功能。结果：EGFR和miR-218- 5 p在砷诱导的转化（As-T）细胞中分别显著上调和下调。MiR-218- 5 p作为肿瘤抑制因子抑制细胞增殖、迁移、集落形成、管形成、肿瘤生长和血管生成。此外，miR-218- 5 p通过结合EGFR的3′-非翻译区（UTR）直接靶向EGFR。最后，miR-218- 5 p通过抑制其直接靶点EGFR发挥其抗肿瘤作用。结论：我们的研究强调了miR-218- 5 p/EGFR信号通路在砷诱导的致癌和血管生成中的重要作用，这可能有助于未来慢性砷暴露诱导的肺癌的治疗。
EGFR upregulation plays an important role in lung cancer as a well-established target for lung cancer therapy. However, the role and mechanism of EGFR upregulation due to chronic arsenic exposure remain to be elucidated. Here, we demonstrated that miR-218-5p was dramatically downregulated in arsenic-induced transformed (As-T) cells. It served as a tumor suppressor to suppress cell proliferation, migration, colony formation, and tube formation, and inhibit tumor growth and angiogenesis by directly targeting EGFR. Our results suggest that the 218-5p/EGFR signaling pathway may be a potential therapeutic target for the treatment of lung cancer induced by chronic arsenic exposure. Background: Arsenic is a well-known carcinogen inducing lung, skin, bladder, and liver cancer. Abnormal epidermal growth factor receptor (EGFR) expression is common in lung cancer; it is involved in cancer initiation, development, metastasis, and treatment resistance. However, the underlying mechanism for arsenic-inducing EGFR upregulation remains unclear. Methods: RT-PCR and immunoblotting assays were used to detect the levels of miR-218-5p and EGFR expression. The Luciferase assay was used to test the transcriptional activity of EGFR mediated by miR-218-5p. Cell proliferation, colony formation, wound healing, migration assays, tube formation assays, and tumor growth assays were used to study the function of miR-218-5p/EGFR signaling. Results: EGFR and miR-218-5p were dramatically upregulated and downregulated in arsenic-induced transformed (As-T) cells, respectively. MiR-218-5p acted as a tumor suppressor to inhibit cell proliferation, migration, colony formation, tube formation, tumor growth, and angiogenesis. Furthermore, miR-218-5p directly targeted EGFR by binding to its 3′-untranslated region (UTR). Finally, miR-218-5p exerted its antitumor effect by inhibiting its direct target, EGFR. Conclusion: Our study highlights the vital role of the miR-218-5p/EGFR signaling pathway in arsenic-induced carcinogenesis and angiogenesis, which may be helpful for the treatment of lung cancer induced by chronic arsenic exposure in the future.
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MicroRNA 在 EGFR 靶向肺癌治疗中的新作用
影响因子：
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作者：
Han F;He J;Li F;Yang J;Wei J;Cho WC;Liu X
通讯作者：
Liu X
影响因子：
6.1
作者：
Banerjee M;Ferragut Cardoso A;Al-Eryani L;Pan J;Kalbfleisch TS;Srivastava S;Rai SN;States JC
通讯作者：
States JC
DOI：
10.1093/toxsci/kfp015
发表时间：
2009-06
期刊：
Toxicological sciences : an official journal of the Society of Toxicology
影响因子：
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作者：
Andrew AS;Mason RA;Memoli V;Duell EJ
通讯作者：
Duell EJ
DOI：
10.1016/j.bbrc.2011.09.102
发表时间：
2011-10-28
影响因子：
3.1
作者：
Carpenter, Richard L.;Jiang, Yue;Jiang, Bing-Hua
通讯作者：
Jiang, Bing-Hua
影响因子：
4.9
作者：
通讯作者：
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