长链非编码RNAMALAT1靶向miR-485-3p调控乳腺癌细胞对紫杉醇的耐药性  

Long-chain non-coding RNA MALAT1 regulates paclitaxel resistance of breast cancer cells by targeting miR-485-3p

作　　者：艾尼·沙塔尔[1] 闫焕英[2] 丁伟[1] 阿迪力江 苏鹏程[1] Aini Shatar;YAN Huanying;DING Wei;Adilijiang;SU Pengcheng(Department of Breast and Thyroid,Northen Branch of Xinjiang Uygur Autonomous Region People's Hospital,Urumqi 830000,China;Department of Nursing,Northen Branch of Xinjiang Uygur Autonomous Region People's Hospital,Urumqi 830000,China)

机构地区：[1]新疆维吾尔自治区人民医院乳腺、甲状腺科,新疆乌鲁木齐830000 [2]新疆维吾尔自治区人民医院北院护理部,新疆乌鲁木齐830000

出　　处：《南方医科大学学报》2020年第5期698-702,共5页Journal of Southern Medical University

摘　　要：目的研究长链非编码RNAMALAT1对乳腺癌细胞紫杉醇耐药性的影响机制。方法运用紫杉醇浓度梯度诱导法检测紫杉醇耐药乳腺癌细胞SK-BR-3;将si-NC组(转染si-NC)、si-MALAT1组(转染si-MALAT1)、pc DNA组(转染pc DNA)、pc DNAMALAT1组(转染pc DNA-MALAT1)、miR-NC组(转染miR-NC)、miR-485-3p组(转染miR-485-3p mimics)、si-MALAT1+antimiR-NC组(共转染si-MALAT1和anti-miR-NC)、si-MALAT1+anti-miR-485-3p组(共转染si-MALAT1和anti-miR-485-3p),均用脂质体法转染SK-BR-3/PR细胞;MTT法检测细胞IC50;Western blot检测细胞中P-gp、Bax、Bcl-2的蛋白表达;双荧光素酶报告基因检测实验检测细胞中MALAT1与miR-485-3p的结合力。结果与紫杉醇敏感SK-BR-3细胞相比,SK-BR-3/PR细胞的IC50、MALAT1均上调,miR-485-3p下调,差异具有统计学意义(P<0.05)。沉默MALAT1或过表达miR-485-3p均可下调SK-BR-3/PR细胞的IC50,下调P-gp和Bcl-2表达,上调Bax表达,差异具有统计学意义(P<0.05)。miR-485-3p是MALAT1的靶标。抑制miR-485-3p可逆转沉默MALAT1对SK-BR-3/PR细胞的IC50、P-gp、Bcl-2和Bax表达的影响,差异具有统计学意义(P<0.05)。结论长链非编码RNAMALAT1可调控乳腺癌细胞对紫杉醇的耐药性,其机制可能与靶向miR-485-3p下调P-gp、Bcl-2,上调Bax有关。Objective To investigate the role of long-chain non-coding RNA MALAT1 in modulating paclitaxel resistance in breast cancer cells.Methods Breast cancer SK-BR-3 cells were treated with gradient concentrations of paclitaxel to induce paclitaxel resistance of the cells.The resistant cells were transfected with si-NC,si-MALAT1,pcDNA,pcDNA-MALAT1,miRNC,miR-485-3p mimics,si-MALAT1+anti-miR-NC,or si-MALAT1+anti-miR-485-3p via liposomes.Following the transfections,the cells were examined for changes in IC50 of paclitaxel using MTT assay;the protein expression of P-gp,Bcl-2 and Bax were detected with Western blotting,and a dual luciferase reporter assay was used to detect the binding of MALAT1 to miR-485-3p.Results Compared with paclitaxel-sensitive SK-BR-3 cells,paclitaxel-resistant SK-BR-3 cells showed significantly increased the IC50 of paclitaxel with up-regulated MALAT1 expression and down-regulated miR-485-3p expression(P<0.05).Silencing MALAT1 or overexpressing miR-485-3p obviously lowered the IC50 of paclitaxel and the expression of P-gp and Bcl-2 and increased the expression of Bax in SK-BR-3/PR cells(P<0.05).miR-485-3p was identified as the target of MALAT1,and inhibiting miR-485-3p significantly reverse the effect of MALAT1 silencing on IC50 of paclitaxel and the expressions of P-gp,Bcl-2 and Bax in SK-BR-3/PR cells(P<0.05).Conclusion MALAT1 can modulate paclitaxel resistance in breast cancer cells possibly by targeting miR-485-3p to down-regulate P-gp and Bcl-2 and up-regulate Bax.

关 键 词：MALAT1 miR-485-3p 紫杉醇耐药 乳腺癌 

分 类 号：R737.9[医药卫生—肿瘤]