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
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篇名: 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
TITLE: Study on mechanism of interfering with LncRNA expressing to reduce paclitaxel resistance in non-small cell lung cancer cells
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(LncRNANNT-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NSCLCTAX耐药细胞系(A549/TAX),检测正常、亲本、耐药细胞中LncRNANNT-AS1的表达情况,并验证miR-582-5p与LncRNANNT-AS1、HMGB2的靶向关系;体外培养A549/TAX细胞,观察单独干扰LncRNANNT-AS1或同时干扰LncRNANNT-AS1、miR-582-5p对细胞中LncRNANNT-AS1、miR-582-5p、HMGB2mRNA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LncRNANNT-AS1对肿瘤生长及肿瘤组织中miR-582-5p、HMGB2mRNA及其蛋白表达的影响。结果与正常细胞比较,LncRNANNT-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LncRNANNT-AS1、HMGB2均存在靶向关系。干扰LncRNANNT-AS1表达后,A549/TAX细胞中LncRNANNT-AS1、HMGB2mRNA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LncRNANNT-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,HMGB2mRNA及其蛋白的表达水平均显著降低(P<0.05)。结论干扰LncRNANNT-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NSCLCTAX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 (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 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 (P<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.
期刊: 2023年第34卷第12期
作者: 靳义;康聪;贺平;王丁丁;杨海龙;陈晓伟
AUTHORS: JIN Yi,KANG Cong,HE Ping,WANG Dingding,YANG Hailong,CHEN Xiaowei
关键字: 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: LncRNA NNT-AS1; mRNA-582-5p; high mobility group box 2; chemotherapy resistance; paclitaxel; non-small
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