MYC通过下调AKR1C1表达抑制肺癌细胞系迁移

doi:10.16352/j.issn.1001-6325.2024.12.1621

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (12): 1621-1627.doi: 10.16352/j.issn.1001-6325.2024.12.1621

• 研究论文 • 下一篇

MYC通过下调AKR1C1表达抑制肺癌细胞系迁移

贾坤, 周妍妍^*

首都医科大学附属北京友谊医院临床检验中心, 北京 100050

收稿日期:2024-08-02 修回日期:2024-09-27 出版日期:2024-12-05 发布日期:2024-11-26
通讯作者: ^*myspur@sina.com
基金资助:
首都卫生发展科研专项重点攻关项目(首发2021-1G-3014)

MYC inhibits migration of lung cancer cell lines by down-regulating AKR1C1 expression

JIA Kun, ZHOU Yanyan^*

Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing 100050,China

Received:2024-08-02 Revised:2024-09-27 Online:2024-12-05 Published:2024-11-26
Contact: ^*myspur@sina.com

摘要/Abstract

摘要： 目的探讨MYC在肺癌细胞迁移中的作用及机制。方法在肺癌细胞系A549中转染MYC siRNA敲降MYC,以及在A549细胞中转染pRK5-MYC质粒过表达MYC,利用伤口愈合试验检测细胞的迁移;利用荧光定量PCR检测候选基因醛酮还原酶(AKR1C1和AKR1C3)mRNA和蛋白水平;利用双荧光素酶报告试验和染色质免疫沉淀试验(ChIP)验证MYC对靶基因的转录调控。A549细胞同时转染MYC和AKR1C1 siRNA或者同时转染pRK5-MYC和pRK5-AKR1C1质粒,利用伤口愈合试验检测细胞的迁移,利用Transwell试验检测细胞的侵袭。结果 A549细胞中敲降MYC促进细胞迁移,过表达MYC抑制细胞迁移。MYC表达降低后AKR1C1的mRNA水平和蛋白质水平均显著升高(P＜0.01)。ChIP试验发现,MYC与AKR1C1基因的反应应答元件(RE)结合。与对照质粒相比,MYC诱导含有RE的质粒表达荧光素酶。AKR1C1表达降低可以抑制肺癌细胞侵袭和迁移(P＜0.05);AKR1C1表达降低也可以减弱MYC缺失引起的细胞侵袭和迁移(P＜0.05)。结论 MYC通过下调AKR1C1的表达抑制体外肺癌细胞系迁移。

关键词: 肺癌细胞, 细胞迁移, MYC, 醛酮还原酶(AKR1C1)

Abstract: Objective To explore the role of MYC in lung cancer cell migration and reveal the mechanism affecting migration. Methods siRNA MYC or pRK5-MYC plasmid was transfected into lung cancer cells A549. Cell migration was examined by wound healing assay. The mRNA expression of candidate genes AKR1C1 and AKR1C3 was detected by fluorescence quantitative PCR. Dual luciferase reporting assay and chromatin immunoprecipitation assay (ChIP) verified the transcriptional regulation of target genes by MYC. A549 cells were transfected with MYC and AKR1C1 siRNA or pRK5-MYC and pRK5-AKR1C1 at the same time. Wound healing assay and Transwell were used to examine cell migration and cell invasion respectively. Results Knockdown MYC in A549 cells promoted cell migration, and over-expression of MYC inhibited cell migration. The level of protein and mRNA of AKR1C1 was significantly increased(P＜0.01) after knockdown MYC. The ChIP assay showed that MYC binded to the response element (RE) of AKR1C1. Compared with control plasmids, MYC induced the expression of luciferase in RE-containing plasmids. Decreased expression of AKR1C1 inhibited the invasion and migration of lung cancer cells(P＜0.05). AKR1C1 reduced cell invasion and migration caused by MYC loss(P＜0.05). Conclusions MYC might inhibit cancer cell migration by inhibiting AKR1C1 expression.

Key words: lung cancer, cell migration, MYC, AKR1C1

中图分类号:

贾坤, 周妍妍. MYC通过下调AKR1C1表达抑制肺癌细胞系迁移[J]. 基础医学与临床, 2024, 44(12): 1621-1627.

JIA Kun, ZHOU Yanyan. MYC inhibits migration of lung cancer cell lines by down-regulating AKR1C1 expression[J]. Basic & Clinical Medicine, 2024, 44(12): 1621-1627.

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MYC通过下调AKR1C1表达抑制肺癌细胞系迁移

MYC inhibits migration of lung cancer cell lines by down-regulating AKR1C1 expression

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