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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
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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 |
| 阅读数： | 121 次 |
| 本月下载数： | 1 次 |
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