Department of Breast and Thyroid Surgery, Shanxian Central Hospital, Heze 274300, China.
Department of Breast and Thyroid Surgery, Shanxian Central Hospital, Heze 274300, China.
Life Sci. 2019 Jul 1;228:135-144. doi: 10.1016/j.lfs.2019.04.063. Epub 2019 May 7.
Drug resistance is becoming a major clinical challenge to the success of breast cancer treatment. Compelling evidence has shown the association between the deregulated long non-coding RNAs (lncRNAs) and drug resistance in various malignancies. However, the effects of long intergenic noncoding RNA 00511 (LINC00511), a newly identified oncogenic lncRNA, on the drug resistance of breast cancer cells remain unknown.
RT-qPCR was performed to detect the expressions of LINC00511, miR-29c, and cyclin dependent kinase 6 (CDK6) in breast cancer tissues and cells. Pearson correlation analysis was used to analyze the correlation between miR-29c, CDK6 and LINC00511 expression in breast cancer tissues. The interactions between LINC00511, CDK6 and miR-29c were explored by luciferase reporter assay, RT-qPCR and western blot. MTT assay and flow cytometry analysis were applied to evaluate paclitaxel cytotoxicity.
LINC00511 and CDK6 were upregulated while miR-29c was downregulated in breast cancer tissues and cells. miR-29c was negatively correlated with LINC00511 and CDK6 expression while LINC00511 was positively correlated with CDK6 expression in breast cancer tissues. LINC0051 directly interacted with miR-29c to suppress its expression. LINC00511 knockdown enhanced paclitaxel cytotoxicity in breast cancer cells by upregulating miR-29c. CDK6 was identified as a target of miR-29c. CDK6 knockdown attenuated the effects of miR-29c inhibition on paclitaxel cytotoxicity in breast cancer cells. LINC00511 positively regulated CDK6 expression in breast cancer cells.
LINC00511 knockdown enhanced paclitaxel cytotoxicity in breast cancer cells via regulating miR-29c/CDK6 axis.
耐药性正成为乳腺癌治疗成功的主要临床挑战。大量证据表明，在各种恶性肿瘤中，失调的长非编码 RNA（lncRNA）与耐药性之间存在关联。然而，长基因间非编码 RNA 00511（LINC00511）的作用，一种新鉴定的致癌 lncRNA，对乳腺癌细胞的耐药性的影响尚不清楚。
采用 RT-qPCR 检测乳腺癌组织和细胞中 LINC00511、miR-29c 和细胞周期蛋白依赖性激酶 6（CDK6）的表达。采用 Pearson 相关性分析乳腺癌组织中 miR-29c、CDK6 和 LINC00511 表达的相关性。采用荧光素酶报告基因检测、RT-qPCR 和 Western blot 探讨 LINC00511、CDK6 和 miR-29c 之间的相互作用。采用 MTT 检测和流式细胞术分析评估紫杉醇细胞毒性。
LINC00511 和 CDK6 在乳腺癌组织和细胞中上调，而 miR-29c 下调。miR-29c 与 LINC00511 和 CDK6 表达呈负相关，而 LINC00511 与乳腺癌组织中 CDK6 表达呈正相关。LINC00511 直接与 miR-29c 相互作用，抑制其表达。LINC00511 敲低通过上调 miR-29c 增强乳腺癌细胞中紫杉醇的细胞毒性。CDK6 被鉴定为 miR-29c 的靶标。CDK6 敲低减弱了 miR-29c 抑制对乳腺癌细胞中紫杉醇细胞毒性的影响。LINC00511 在乳腺癌细胞中正向调节 CDK6 表达。
LINC00511 敲低通过调节 miR-29c/CDK6 轴增强乳腺癌细胞中紫杉醇的细胞毒性。
