IL⁃17诱导的p300调控NSCLC细胞迁移、侵袭和MMP2表达的作用
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国家自然科学基金(81902878)


IL⁃17⁃induced p300 regulates the migration,invasion and MMP2 production of NSCLC cells
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    摘要:

    目的:探讨IL-17刺激非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞上调腺病毒E1A相关300 kDa蛋白(adenoviral E1A binding protein of 300 kDa,p300)调控其细胞迁移、侵袭及生成基质金属蛋白酶2(matrix metalloproteinase 2,MMP2)的作用。方法:用IL-17刺激 NSCLC细胞(H1299)后行划痕和Transwell实验观察细胞迁移和侵袭的变化。然后用Western blot检查p300和MMP2蛋白的表达。同时,将p300过表达质粒(pcDNA3.1/p300)或shp300干扰质粒分别转染H1299细胞(后者再行IL-17刺激),用前述方法测定细胞迁移、侵袭和MMP2的表达。结果:用IL-17刺激H1299细胞后能显著诱导其迁移和侵袭,并上调p300和MMP2的表达。过表达p300可增强细胞的迁移与侵袭,并提高MMP2的生成,但沉默p300基因后由IL-17诱导的细胞迁移和侵袭能力及MMP2的表达均显著降低。结论:IL-17上调的p300能促进H1299细胞的迁移与侵袭以及MMP2基因的表达。

    Abstract:

    Objective:This study aims to investigate the effects of adenovirus E1A associated 300 kDa protein(p300) on the migration,invasion and matrix metalloproteinase-2(MMP2) expression in non-small cell lung cancer(NSCLC) cells stimulated by IL-17. Methods:After NSCLC cells(H1299) incubated with IL-17,scratch and transwell experiments were performed to observe the cell migration and invasion. Then the p300 and MMP2 protein expression was detected using Western blot. Meantime,p300 overexpression plasmids(pcDNA3.1/p300) or short hairpin RNA(shp300) plasmids were transfected into H1299 cells(the latter was stimulated with IL-17),respectively,and the cell migration,invasion and MMP2 synthesis were again examined by the same method described above. Results:The migration and invasion as well as the expression of p300 and MMP2 were obviously elevated in H1299 cells treated by IL-17. And p300 overexpression significantly promoted the cell migration,invasion,and MMP2 expression. While p300 gene knockdown by shp300 led to the decrease of migration,invasion and MMP2 production in H1299 cells induced by IL-17. Conclusion:IL-17-upregulates p300 in H1299 cells which enhances the cell migration,invasion and MMP2 expression.

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李 雅,葛 文,张志伟,蒋馨怡,何庆玲,阮玉婷,吴宁霞,应 帅,王伟民,张 婧,邱 文,王迎伟,赵晨卉. IL⁃17诱导的p300调控NSCLC细胞迁移、侵袭和MMP2表达的作用[J].南京医科大学学报(自然科学版),2022,42(2):160-165

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  • 收稿日期:2021-11-23
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  • 在线发布日期: 2022-03-01
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