干扰LncRNA表达减轻非小细胞肺癌细胞对紫杉醇耐药的机制研究

靳义; 康聪; 贺平; 王丁丁; 杨海龙; 陈晓伟

doi:10.6039/j.issn.1001-0408.2023.12.10

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干扰LncRNA表达减轻非小细胞肺癌细胞对紫杉醇耐药的机制研究

药学研究 | 更新时间：2023-06-26

- 干扰LncRNA表达减轻非小细胞肺癌细胞对紫杉醇耐药的机制研究
- Study on mechanism of interfering with LncRNA expressing to reduce paclitaxel resistance in non-small cell lung cancer cells
- 中国药房 2023年34卷第12期页码：1460-1467
- 作者机构：
  
  衡水市人民医院胸外科，河北衡水　053000
- 作者简介：
  
  主治医师，硕士。研究方向：进展期非小细胞肺癌化疗获益相关标志物。电话：0318-2181128。E-mail：122161932@qq.com
  副主任医师。研究方向：进展期非小细胞肺癌化疗获益相关标志物。电话：0318-2181128。E-mail：wcliangzi@163.com
- 基金信息：
  
  衡水市市级科技计划项目(2020014054Z)
- DOI：10.6039/j.issn.1001-0408.2023.12.10
  中图分类号： R965
- 纸质出版日期：2023-06-30，
  
  收稿日期：2022-11-12，
  
  修回日期：2023-04-03，
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靳义,康聪,贺平等.干扰LncRNA表达减轻非小细胞肺癌细胞对紫杉醇耐药的机制研究 ^Δ[J].中国药房,2023,34(12):1460-1467.

JIN Yi,KANG Cong,HE Ping,et al.Study on mechanism of interfering with LncRNA expressing to reduce paclitaxel resistance in non-small cell lung cancer cells[J].ZHONGGUO YAOFANG,2023,34(12):1460-1467.
靳义,康聪,贺平等.干扰LncRNA表达减轻非小细胞肺癌细胞对紫杉醇耐药的机制研究 ^Δ[J].中国药房,2023,34(12):1460-1467. DOI： 10.6039/j.issn.1001-0408.2023.12.10.

JIN Yi,KANG Cong,HE Ping,et al.Study on mechanism of interfering with LncRNA expressing to reduce paclitaxel resistance in non-small cell lung cancer cells[J].ZHONGGUO YAOFANG,2023,34(12):1460-1467. DOI： 10.6039/j.issn.1001-0408.2023.12.10.

摘要

目的

研究干扰长链非编码RNA烟酰胺核苷酸转氢酶反义RNA1（LncRNA NNT-AS1）表达减轻非小细胞肺癌（NSCLC）细胞对紫杉醇（TAX）耐药的机制。

方法

构建NSCLC TAX耐药细胞系（A549/TAX），检测正常、亲本、耐药细胞中LncRNA NNT-AS1的表达情况，并验证miR-582-5p与LncRNA NNT-AS1、HMGB2的靶向关系；体外培养A549/TAX细胞，观察单独干扰LncRNA NNT-AS1或同时干扰LncRNA NNT-AS1、miR-582-5p对细胞中LncRNA NNT-AS1、miR-582-5p、HMGB2 mRNA及其蛋白表达以及细胞活力、克隆形成、凋亡的影响；通过裸鼠成瘤实验观察干扰LncRNA NNT-AS1对肿瘤生长及肿瘤组织中miR-582-5p、HMGB2 mRNA及其蛋白表达的影响。

结果

与正常细胞比较，LncRNA NNT-AS1在亲本、耐药细胞中均呈高表达（

＜0.05），且有递增趋势。经验证，miR-582-5p与LncRNA NNT-AS1、HMGB2均存在靶向关系。干扰LncRNA NNT-AS1表达后，A549/TAX细胞中LncRNA NNT-AS1、HMGB2 mRNA及其蛋白的表达水平以及细胞活力、克隆形成数均显著降低，而miR-582-5p的表达水平、细胞凋亡率均显著升高（

＜0.05）；同时干扰miR-582-5p表达可使上述改变得以逆转（

＜0.05）。干扰肿瘤细胞中LncRNA NNT-AS1的表达后，荷瘤裸鼠的肿瘤体积和肿瘤质量均显著降低，miR-582-5p的表达水平显著升高，HMGB2 mRNA及其蛋白的表达水平均显著降低（

＜0.05）。

结论

干扰LncRNA NNT-AS1的表达可靶向上调miR-582-5p的表达并下调HMGB2的表达，进而减轻NSCLC TAX化疗耐药。

Abstract

OBJECTIVE

To study the mechanism of interfering with long non-coding RNA nicotinamide nucleotide transhydrogenase-antisense RNA1 （LncRNA NNT-AS1） expressing to reduce paclitaxel （TAX） resistance in non-small cell lung cancer （NSCLC） cells.

METHODS

NSCLC TAX-resistant cell line （A549/TAX） was constructed， and the expressions of LncRNA NNT-AS1 in normal， parental， and drug-resistant cells were observed. The targeting relationship of microRNA-582-5p （miR-582-5p） with LncRNA NNT-AS1 and high mobility group box2 （HMGB2） was verified. A549/TAX cells were cultured

in vitro

to observe the effects of interfering with LncRNA NNT-AS1 alone or interfering with LncRNA NNT-AS1 and miR-582-5p on the expressions of LncRNA NNT-AS1 and miR-582-5p， the mRNA and protein expressions of HMGB2， cell viability， clone formation and apoptosis. The effects of interfering with LncRNA NNT-AS1 on tumor growth and the expression of miR-582-5p and the mRNA and protein expressions of HMGB2 in tumor tissue were observed in nude mice.

RESULTS

Compared with normal cells， LncRNA NNT-AS1 was highly expressed in parental and drug-resistant cells （

＜0.05）， showing an increasing trend. It was validated that miR-582-5p had a targeting relationship with LncRNA NNT-AS1 and HMGB2. After interfering with the expression of LncRNA NNT-AS1， the expression of LncRNA NNT-AS1 and the mRNA and protein expressions of HMGB2， cell viability and the number of cloned cells in A549/TAX cell， decreased significantly， while the expression of miR-582-5p and the apoptotic rate increased significantly （

＜0.05）； simultaneously interfering with the expression of miR-582-5p could reverse above changes （

＜0.05）. Interfering with the expression of LncRNA NNT-AS1 in tumor cell could significantly reduce tumor volume and tumor weight of nude mice bearing tumors； at the same time， the expression of miR-582-5p was up-regulated significantly and the mRNA and protein expressions of HMGB2 were down-regulated significantly （

＜0.05）.

CONCLUSIONS

Interfering with the expression of LncRNA NNT-AS1 may alleviate TAX chemotherapy resistance in NSCLC through targeted up-regulation of miR-582-5p and down-regulation of HMGB2.

关键词

长链非编码RNA烟酰胺核苷酸转氢酶反义RNA1微RNA-582-5p高迁移率族蛋白2化疗耐药紫杉醇非小细胞肺癌

Keywords

mRNA-582-5phigh mobility group box 2chemotherapy resistancepaclitaxelnon-small cell lung cancer

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