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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
Δ
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靳 义 ，康 聪，贺 平，王丁丁，杨海龙，陈晓伟（衡水市人民医院胸外科，河北 衡水 053000）
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中图分类号 R965 文献标志码 A 文章编号 1001-0408（2023）12-1460-08
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（P＜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（P＜0.05）；同时干扰miR-582-5p表达可使上述改变得以逆转（P＜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（P＜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。
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
Study on mechanism of interfering with LncRNA expressing to reduce paclitaxel resistance in non-small
cell lung cancer cells
JIN Yi，KANG Cong，HE Ping，WANG Dingding，YANG Hailong，CHEN Xiaowei（Dept. of Thoracic Surgery，
Hengshui People’s Hospital， Hebei Hengshui 053000， China）
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 （P＜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 （P＜0.05）； simultaneously interfering with the expression of miR-582-5p could reverse above changes （P＜
0.05）. Interfering with the expression of LncRNA NNT-AS1 in
Δ 基金项目 衡水市市级科技计划项目（No.2020014054Z） tumor cell could significantly reduce tumor volume and tumor
＊第一作者 主治医师，硕士。研究方向：进展期非小细胞肺癌化 weight of nude mice bearing tumors； at the same time， the
疗获益相关标志物。电话：0318-2181128。E-mail：122161932@qq.com
expression of miR-582-5p was up-regulated significantly and
# 通信作者 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 the mRNA and protein expressions of HMGB2 were down-
· 1460 · China Pharmacy 2023 Vol. 34 No. 12 中国药房 2023年第34卷第12期
