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KLF5 influences cell biological function and chemotherapy sensitivity through the JNK signaling pathway in anaplastic thyroid carcinoma

机译:KLF5通过JNK信号传导途径对细胞生物功能和化疗敏感性感受到激动的甲状腺癌

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We aimed to investigate the effects of Kruppel-like factor 5 (KLF5) on cell biological function and chemotherapy sensitivity of anaplastic thyroid carcinoma (ATC) and explore the underlying mechanism. In this study, we found that KLF5 was expressed higher in ATC cells than that in normal thyroid cells. Knockdown of KLF5 inhibited proliferation, induced apoptosis and restrained invasion and migration abilities of ATC cells. KLF5 overexpression promoted proliferation and inhibited apoptosis of ATC cells in response to doxorubicin (Dox), whereas KLF5 knockdown increased the sensitivity of ATC cells to Dox. Multidrug resistance gene 1/permeability glycoprotein and ATP-binding cassette super-family G member 2 were heightened in ATC cells with KLF5 overexpression, but the opposite results were found in sh-KLF5-treated cells. Phosphorylation (p)-c-Jun N-terminal kinase (JNK) was upregulated in KLF5 overexpression cells, whereas it was downregulated in the KLF5 knockdown treatment group. Furthermore, KLF5 knockdown inhibited ATC growth and enhanced the Dox sensitivity of ATC by inactivating the JNK signaling pathway. Taken together, our findings concluded that KLF5 knockdown can remarkably inhibit the proliferation, invasion, and migration and induce apoptosis of ATC cells, and increase the chemotherapy sensitivity of ATC, all of which probably through inhibiting the JNK signaling pathway.
机译:我们旨在研究Kruppel样因子5(KLF5)对间变性甲状腺癌(ATC)细胞生物学功能和化疗敏感性的影响,并探讨其潜在机制。在这项研究中,我们发现KLF5在ATC细胞中的表达高于正常甲状腺细胞。敲除KLF5可抑制ATC细胞的增殖,诱导凋亡,抑制其侵袭和迁移能力。KLF5的过度表达促进了ATC细胞对阿霉素(Dox)的增殖并抑制其凋亡,而KLF5的敲除增加了ATC细胞对Dox的敏感性。多药耐药基因1/通透性糖蛋白和ATP结合盒超家族G成员2在KLF5过度表达的ATC细胞中升高,但在sh-KLF5处理的细胞中发现相反的结果。磷酸化(p)-c-Jun N-末端激酶(JNK)在KLF5过表达细胞中上调,而在KLF5敲除治疗组中下调。此外,KLF5基因敲除通过使JNK信号通路失活而抑制ATC生长并增强ATC对Dox的敏感性。综上所述,我们的研究结果表明,KLF5基因敲除可显著抑制ATC细胞的增殖、侵袭和迁移,诱导其凋亡,并提高ATC的化疗敏感性,所有这些可能都是通过抑制JNK信号通路实现的。

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