LINC00511 knockdown enhances paclitaxel cytotoxicity in breast cancer via regulating miR-29c/CDK6 axis

• Published in: Life sciences (1973) Vol. 228; pp. 135 - 144
• Main Authors: Zhang, Hualong, Zhao, Bin, Wang, Xiuxia, Zhang, Fan, Yu, Wenlong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.07.2019; Elsevier BV
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; CDK6; Cell Line, Tumor; Correlation analysis; Cyclin-Dependent Kinase 6 - genetics; Cytotoxicity; Deregulation; Drug resistance; Female; Flow cytometry; Gene Expression Regulation, Neoplastic - drug effects; Gene Knockdown Techniques; Humans; Kinases; LINC00511; MicroRNAs - genetics; Middle Aged; miR-29c; Paclitaxel; Paclitaxel - pharmacology; Paclitaxel cytotoxicity; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; Target recognition; Tissues; Toxicity; miR-29c; Paclitaxel cytotoxicity; Breast cancer; CDK6; LINC00511
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2019.04.063

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.