敲低DRAM2抑制肺癌细胞系A549的增殖和迁移

doi:10.16352/j.issn.1001-6325.2025.02.0197

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (2): 197-202.doi: 10.16352/j.issn.1001-6325.2025.02.0197

敲低DRAM2抑制肺癌细胞系A549的增殖和迁移

楼海均¹, 童卓云¹, 张振宇¹, 阿合叶尔克·马合沙提¹, 孟·孟根², 乌都木丽^1*

新疆医科大学 1.基础医学院病理教研室;
2.第五临床医学院检验科,新疆乌鲁木齐 830017

收稿日期:2024-07-01 修回日期:2024-10-31 出版日期:2025-02-05 发布日期:2025-01-17
通讯作者: ^*wudumuli@xjmu.edu.cn
基金资助:
新疆维吾尔自治区重点研发计划(2022B03019-1-1);新疆维吾尔自治区自然科学基金青年科学基金项目(2020D01C175)

Knockdown of DRAM2 inhibits the proliferation and migration of lung cancer cell line A549

LOU Haijun¹, TONG Zhuoyun¹, ZHANG Zhenyu¹, Aheyerk·MAHESHATI¹, MENG·Menggen², WUDU Muli^1*

1. Department of Pathology, School of Basic Medicine;
2. Department of Clinical Laboratory, the Fifth Clinical College of Medicine, Xinjiang Medical University, Urumqi 830017, China

Received:2024-07-01 Revised:2024-10-31 Online:2025-02-05 Published:2025-01-17
Contact: ^*wudumuli@xjmu.edu.cn

摘要/Abstract

摘要： 目的探讨DNA损伤调节自噬因子2(DRAM2)如何通过调节p53和自噬对非小细胞肺癌(NSCLC)细胞增殖和迁移的影响。方法利用慢病毒技术敲低A549细胞系DRAM2基因,免疫荧光和Western blot检测自噬标志物。CCK8和Transwell实验检测细胞增殖和迁移,同时探究激活自噬和p53敲低对DRAM2敲低细胞自噬及功能的影响。结果敲低DRAM2抑制A549细胞p62表达上调(P＜0.05)和LC3-Ⅱ降低(P＜0.05)。敲低DRAM2抑制了NSCLC细胞的增殖(P＜0.001)和迁移(P＜0.001)。激活自噬能够部分消除敲低DRAM2对细胞增殖(P＜0.01)和迁移(P＜0.01)的抑制作用。当DRAM2和p53同时敲低时,恢复自噬、细胞增殖(P＜0.05)和迁移能力(P＜0.001)。结论敲低DRAM2抑制肺瘤细胞系A549的增殖和迁移,为未来非小细胞肺癌的治疗策略提供了可能的干预方向。

关键词: 非小细胞肺癌, DNA损伤调节自噬调节因子2(DRAM2), 肿瘤蛋白p53, 自噬

Abstract: Objective To investigate the impact of DNA damage-regulated autophagy factor 2 (DRAM2) on the proliferation and migration of non-small cell lung cancer (NSCLC) cells through tumor protein p53 (p53) and autophagy. Methods DRAM2 gene was knocked down using lentiviral technology to establish NSCLC cell lines, and autophagy markers were detected by immunofluorescence and Western blot. CCK8 and Transwell assays were used to detect cell proliferation and migration. The effects of autophagy activation and p53 knockdown on autophagy and functions of DRAM2-knockdown cells were examined. Results Knockdown of DRAM2 inhibited NSCLC cells, with upregulation of p62 expression (P＜0.05) and decreased level of LC3-Ⅱ (P＜0.05).Knockdown of DRAM2 suppressed the proliferation (P＜0.001) and migration (P＜0.001) of NSCLC cells. Activation of auto- phagy partially reversed the inhibitory effects of DRAM2 knockdown on cell proliferation (P＜0.01) and migration (P＜0.01).When DRAM2 and p53 were knocked down simultaneously, autophagy, cell proliferation (P＜0.05) and migration abilities (P＜0.001) were restored. Conclusions Knockdown of DRAM2 inhibits the proliferation and migration of lung cancer cell line A549, providing a potential intervention direction for the development of therapeutic strategies.

Key words: non-small cell lung cancer, DRAM2, p53, autophagy

中图分类号:

楼海均, 童卓云, 张振宇, 阿合叶尔克·马合沙提, 孟·孟根, 乌都木丽. 敲低DRAM2抑制肺癌细胞系A549的增殖和迁移[J]. 基础医学与临床, 2025, 45(2): 197-202.

LOU Haijun, TONG Zhuoyun, ZHANG Zhenyu, Aheyerk·MAHESHATI, MENG·Menggen, WUDU Muli. Knockdown of DRAM2 inhibits the proliferation and migration of lung cancer cell line A549[J]. Basic & Clinical Medicine, 2025, 45(2): 197-202.

参考文献 15

[1]	Leiter A, Veluswamy RR, Wisnivesky JP. The global burden of lung cancer: current status and future trends[J]. Nat Rev Clin Oncol, 2023, 20: 624-639.
[2]	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71: 209-249.
[3]	Li C, Lei S, Ding L, et al. Global burden and trends of lung cancer incidence and mortality[J]. Chin Med J, 2023, 136: 1583-1590.
[4]	Luo X, Wang J, Wang R, et al. Sll-1a-16 suppresses proliferation and induces autophagy in non-small-cell lung cancer cells via the AKT/mTOR signaling pathway[J]. RSC Med Chem, 2024, 15: 15:3460-3468. doi: 10.1039/d4md00405a
[5]	Wudu M, Ren H, Hui L, et al. DRAM2 acts as an oncogene in non-small cell lung cancer and suppresses the expression of p53[J]. J Exp Clin Cancer Res, 2019, 38: 72. doi:10.1186/s13046-019-1068-4.
[6]	Yamamoto H, Zhang S, Mizushima N. Autophagy genes in biology and disease[J]. Nat Rev Genet Genetics, 2023, 24: 382-400.
[7]	Koutsifeli P, Varma U, Daniels LJ, et al. Glycogen-autophagy: molecular machinery and cellular mechanisms of glycophagy[J]. J Biol Chem, 2022, 298: 102093.doi: 10.1016/j.jbc.2022.102093.
[8]	Li L, Wang X, Jiang M, et al. Advancements in a novel model of autophagy and immune network regulation in radioresistance of cancer stem cells[J]. Biomed Pharmacother, 2024, 179: 117420.doi: 10.1016/j.jbc.2022.102093.
[9]	Xia H, Green DR, Zou W. Autophagy in tumour immunity and therapy[J]. Nat Rev Cancer, 2021, 21: 281-297.
[10]	Rahman MA, Park MN, Rahman MH, et al. P53 modulation of autophagy signaling in cancer therapies: perspectives mechanism and therapeutic targets[J]. Front Cell Dev Biol, 2022, 10: 761080. doi:10.3389/fcell.2022.761080.
[11]	Xu J, Patel NH, Gewirtz DA. Triangular relationship between p53, autophagy, and chemotherapy resistance[J]. Int J Mol Sci, 2020, 21:8991. doi:10.3390/IJMS21238991.
[12]	Nahálková J. On the interface of aging, cancer, and neurodegeneration with sirt6 and l1 retrotransposon protein interaction network[J]. Ageing Res Rev, 2024: 102496. doi:10.1016/j.arr.2024.102496.
[13]	Wen W, Zhang WL, Tan R, et al. Progress in deciphering the role of p53 in diffuse large B-cell lymphoma: mechanisms and therapeutic targets[J]. Am J Cancer Res, 2024, 14: 3280-3293.
[14]	Wang H, Chen Q, Liu Q, et al. Master regulator: p53's pivotal role in steering NK-cell tumor patrol[J]. Front Immunol, 2024, 15: 1428653. doi:10.3389/fimmu.2024.1428653.
[15]	Veneziani I, Infante P, Ferretti E, et al. Nutlin-3a enhances natural killer cell-mediated killing of neuroblastoma by restoring p53-dependent expression of ligands for NKG2D and DNAM-1 receptors[J]. Cancer Immunol Res, 2021, 9: 170-183.

编辑推荐 0

Metrics

阅读次数

全文

HTML			PDF

最新录用	在线预览	正式出版	最新录用	在线预览	正式出版
0	0	0	0	0	20

	来源	本网站

	次数	20
	比例	100%

摘要

最新录用	在线预览	正式出版

0	0	69

	来源	本网站

	次数	69
	比例	100%

敲低DRAM2抑制肺癌细胞系A549的增殖和迁移

Knockdown of DRAM2 inhibits the proliferation and migration of lung cancer cell line A549

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 15

相关文章 15

编辑推荐 0

Metrics

本文评价

[1]	庞昀婷, 任晓爽, 包涵, 孟凡青, 石枫. 左西孟旦减轻模型大鼠离体心脏停灌/再灌注损伤[J]. 基础医学与临床, 2025, 45(1): 65-69.
[2]	祖力皮亚·阿布拉, 赵强, 张泰民, 李甜. 马里苷减轻高糖诱导的大鼠心肌细胞系H9c2损伤[J]. 基础医学与临床, 2024, 44(9): 1269-1273.
[3]	周昌东, 林洋, 孙凯, 田玉新. 敲降lncRNA UCA1降低人膀胱癌细胞系T24对吉西他滨耐药[J]. 基础医学与临床, 2024, 44(8): 1113-1119.
[4]	郑红, 陈晓霞, 韩李周, 陈苗, 皇甫娟. 降低lncRNA-RMRP表达抑制人肺癌细胞系A549的增殖和侵袭[J]. 基础医学与临床, 2024, 44(7): 974-978.
[5]	张祥鑫, 李文. 线粒体自噬在肝脏缺血再灌注损伤中的作用[J]. 基础医学与临床, 2024, 44(6): 877-881.
[6]	张玉苓, 张珂, 许艇, 张庆. 胎儿生长受限孕妇胎盘自噬相关蛋白表达水平及其临床意义[J]. 基础医学与临床, 2024, 44(4): 528-532.
[7]	梁香存, 魏小雨, 梁健, 王庆, 耿广. 安罗替尼通过调控miR-16-5p/PD-1轴抑制人非小细胞肺癌细胞系增殖并促进凋亡[J]. 基础医学与临床, 2024, 44(4): 503-512.
[8]	杨铠菲, 朱静格, 张洋洋, 赵俊果, 高雨悦, 胡焕焕, 姬国杰. 索拉菲尼诱导的细胞凋亡和自噬对HeLa细胞耐药性的影响[J]. 基础医学与临床, 2024, 44(4): 467-473.
[9]	张婧, 杨自更, 蔡文琴, 曹维维, 韦红梅, 薛茜茜, 吴宾. 抑制抗增殖蛋白2增强非小细胞肺癌细胞系A549对厄洛替尼敏感性[J]. 基础医学与临床, 2024, 44(3): 325-332.
[10]	李娟, 李晓峰, 徐生志, 唐凯. 华蟾素胶囊联合多西紫杉醇+顺铂化疗用于非小细胞肺癌患者的疗效[J]. 基础医学与临床, 2024, 44(2): 247-251.
[11]	丁飞, 王洒, 黄常新. 非小细胞肺癌患者血清CA211水平和NK细胞数与预后相关[J]. 基础医学与临床, 2024, 44(2): 180-184.
[12]	张进芳, 钟明艳, 杨泉, 冯贝, 李兴东. 下调ATM/hnRNPK信号降低髓系白血病细胞阿霉素耐药[J]. 基础医学与临床, 2024, 44(12): 1638-1643.
[13]	田宗源, 李展, 刘瑞霞. TERT调控线粒体氧化应激在疾病中的作用[J]. 基础医学与临床, 2024, 44(10): 1436-1441.
[14]	张伟, 张振, 杨连任, 梁伟. 肺癌7项抗体水平与NSCLC患者化疗效果及预后的关系[J]. 基础医学与临床, 2024, 44(10): 1383-1387.
[15]	王春燕, 王萍, 宋龙飞, 刘永全, 满君. LncRNA FEZF1-AS1通过调控EZH2对肺间质细胞增殖、迁移及侵袭的作用[J]. 基础医学与临床, 2024, 44(1): 43-50.