Increased MALAT1 expression contributes to cisplatin resistance in non‑small cell lung cancer

Cui,Yong; Li,Guanlong; Zhang,Xin; Dai,Fangfang; Zhang,Rongxiang

doi:10.3892/ol.2018.9293

Increased MALAT1 expression contributes to cisplatin resistance in non‑small cell lung cancer

Authors:
- Yong Cui
- Guanlong Li
- Xin Zhang
- Fangfang Dai
- Rongxiang Zhang
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Affiliations: The Third Department of Oncology, Shouguang People's Hospital, Shouguang, Shandong 262700, P.R. China
Published online on: August 10, 2018 https://doi.org/10.3892/ol.2018.9293
Pages: 4821-4828
Copyright: © Cui et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cisplatin‑based chemotherapy is commonly used for the clinical treatment of patients with non‑small cell lung cancer (NSCLC). However, the anti‑tumor efficacy of cisplatin is limited by poor clinical response and the development of chemoresistance. At present, the underlying mechanism for cisplatin resistance remains unclear. In the present study, it was identified that metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1), a long non‑coding RNA that has been demonstrated to function as an oncogene, was increased in tumor tissues from patients with cisplatin‑resistant NSCLC. In addition, the MALAT1 level was increased in A549rCDDP cells compared with the parental A549 cells. Silencing of MALAT1 sensitized A549rCDDP cells to cisplatin treatment, while overexpression of MALAT1 in A549 cells decreased their sensitivity towards cisplatin. Through analysis of the gene expression in patient samples, a decrease in miR‑145 and an increase in Kruppel‑like factor 4 (KLF4) in tumor tissues compared with adjacent normal tissues was observed. A negative association between MALAT1 and miR‑145 was also identified in A549 cells and A549rCDDP cells. Furthermore, reverse transcription quantitative polymerase chain reaction and western blotting identified that KLF4 was positively and negatively regulated by MALAT1 and miR‑145, respectively. The direct regulatory association between MALAT1 and miR‑145 and the target gene KLF4 was additionally confirmed using a luciferase reporter assay. Knockdown of MALAT1 reversed cisplatin resistance in A549rCDDP cells. Taken together, these data indicated that MALAT1 decreased the sensitivity of NSCLC to cisplatin via the regulation of miR‑145 and KLF4.

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