Upregulation of Long Noncoding RNA (lncRNA) X-Inactive Specific Transcript (XIST) is Associated with Cisplatin Resistance in Non-Small Cell Lung Cancer (NSCLC) by Downregulating MicroRNA-144-3p
| Autor: | Dong Wang, Dong-Yue Zhang, Wei Liu, Lin-Juan Tian, Yun-Ping Wu, Yong-Gang Wei, Zhi-He Zhou, Shou-Bin Xue |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
ATP Binding Cassette Transporter
Subfamily B Lung Neoplasms endocrine system diseases non-small cell lung cancer (NSCLC) Mice Nude Antineoplastic Agents Apoptosis 030204 cardiovascular system & hematology 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Carcinoma Non-Small-Cell Lung Cell Line Tumor microRNA medicine Animals Humans Molecular Biology Cell Proliferation A549 cell Cisplatin Mice Inbred BALB C Chemistry General Medicine medicine.disease Xenograft Model Antitumor Assays Long non-coding RNA respiratory tract diseases Reverse transcription polymerase chain reaction MicroRNAs A549 Cells Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research XIST Female RNA Long Noncoding medicine.drug Signal Transduction |
| Zdroj: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
| ISSN: | 1643-3750 1234-1010 |
| Popis: | BACKGROUND Patients with advanced non-small cell lung cancer (NSCLC) treated with cisplatin, also termed cis-diamminedichloroplatinum (CDDP) or diamminedichloroplatinum (DDP), may develop chemoresistance. This study aimed to investigate the role of long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) and multidrug resistance-1 (MDR1) in tumor tissue samples and the chemoresistant human NSCLC cell lines, H460/DDP and A549/DDP, and in a murine A549/DDP tumor xenograft. MATERIAL AND METHODS Tissue samples were from patients with NSCLC who responded cisplatin (DDP-sensitive) (n=24), patients with NSCLC unresponsive to cisplatin (DDP-resistant) (n=30), and normal lung tissue (n=25). In H460/DDP and A549/DDP cells, expression of XIST, microRNA (miR)-144-3p, MDR1, and multidrug resistance-associated protein 1 (MRP1) were detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The MTT assay measured cell survival and proliferation, a transwell assay evaluated cell migration, and flow cytometry measured apoptosis. Luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays examined the relationship between XIST and miR-144-3p. Tumor xenografts from A549/DDP cells were studied in BALB/c nude mice. RESULTS In tissue from patients with DDP-resistant NSCLC and the mouse A549/DDP tumor xenograft, lncRNA-XIST expression was upregulated and miR-144-3p expression was inhibited. In A549/DDP and H460/DDP cells, down-regulation of lncRNA-XIST and upregulation of miR-144-3p reduced cell survival, proliferation, migration, induced apoptosis and suppressed MDR1 and MRP1 expression. CONCLUSIONS Upregulation of lncRNA-XIST was associated with cisplatin resistance in NSCLC by downregulating miRNA-144-3p in H460/DDP and A549/DDP cells, a murine A549/DDP tumor xenograft, and human tumor tissues from patients with cisplatin-resistant NSCLC. |
| Databáze: | OpenAIRE |
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