miR-298通过抑制TAZ改善耐药肺癌细胞株的耐药性

miR-298 Improving Drug Resistance of Drug-Resistant Lung Cancer Cell Lines by In-hibiting TAZ

目的:寻找在肺癌耐药性生成中起到调节作用的miRNA,研究miR-298在肺癌耐药细胞株中的表达规律及作用,探讨miR-298通过靶向TAZ调节耐药肺癌细胞株的作用,为肺癌寻找新的治疗靶点。方法:利用生物信息学技术分析顺铂耐药与敏感的肺癌病人中差异表达的miRNA,通过建立顺铂耐药的肺癌细胞株模型,验证miR-298表达下调。利用miR-298 mimics转染,验证miR-298对耐药肺癌细胞株的作用,通过转染WB,RT-PCR、双荧光素酶报告实验验证miR-298对TAZ的靶向调控作用,通过转染TAZ-siRNA检测TAZ在肺癌耐药株中的作用。结果:我们通过生物信息学技术发现miR-298在顺铂耐药的肺癌病人标本中低表达,在顺铂耐药肺癌细胞呈低表达,通过miR-298 mimics转染可以增高miR-298的表达量,可以在一定程度上改善顺铂的耐药性,同时抑制细胞的克隆形成。TAZ在肺癌耐药细胞中表达增高,miR-298可以靶向下调TAZ的表达,而敲低顺铂耐药细胞株中的TAZ,可以改善顺铂耐药,抑制细胞克隆形成。结论:miR-298在肺癌耐药中发挥重要的调节作用,通过上调miR-298可以改善肺癌的耐药性,miR-298可能是通过靶向抑制TAZ发挥作用的。

Objective: To find miRNAs that play a regulatory role in the generation of lung cancer drug re-sistance, to study the expression and role of miR-298 in lung cancer drug-resistant cell lines, and to explore the role of miR-298 in regulating drug-resistant lung cancer cell lines by targeting TAZ, To find new therapeutic targets for lung cancer. Methods: Using bioinformatics technology to analyze the differentially expressed miRNAs in cisplatin-resistant and sensitive lung cancer patients, and establish a cisplatin-resistant lung cancer cell line model to verify the down-regulation of miR-298. Transfection with miR-298 mimics was used to verify the effect of miR-298 on drug-resistant lung cancer cell lines. The targeted regulation of miR-298 on TAZ was verified by transfection of WB, RT-PCR, and dual luciferase report experiments. TAZ-siRNA was used to detect the role of TAZ in drug-resistant lung cancer strains. Results: Through bioinformatics technology, we found that miR-298 is low in cisplatin-resistant lung cancer patient specimens and low in cisplatin-resistant lung cancer cells. Transfection with miR-298 mimics can increase the expression of miR-298 the amount can improve the drug resistance of cisplatin to a certain extent, while inhibiting the for-mation of cell clones. TAZ expression is increased in lung cancer drug-resistant cells, miR-298 can target down-regulation of TAZ expression, and knocking down TAZ in cisplatin-resistant cell lines can improve cisplatin resistance and inhibit cell clone formation. Conclusion: miR-298 plays an im-portant regulatory role in lung cancer drug resistance. Up-regulating miR-298 can improve lung cancer drug resistance, and miR-298 may play a role through targeted inhibition of TAZ.