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Knockdown of long non-coding RNA KCNQ1OT1 depressed chemoresistance to paclitaxel in lung adenocarcinoma

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Abstract

Lung cancer, with the highest morbidity and second highest death rates, is one of the most common cancers in both males and females worldwide. Lung adenocarcinoma (LAD) is the main lung cancer class. KCNQ1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1) gene is an lncRNA which had been reported high-expression in colorectal cancer. In this study, the expression of KCNQ1OT1 was confirmed to be highly expressed in LAD tissues and cells contrast to control tissues and cells, and high KCNQ1OT1 expression correlated to malignant behaviors of LAD, including big tumor size, poor differentiation, positive lymphatic metastasis and high TNM stages. The transfection of si-KCNQ1OT1 could effectually knockdown the expression of KCNQ1OT1 in A549 and A549/PA cells. The KCNQ1OT1 knockdown depressed the proliferation and invasion of A549 cells, and advanced cellular apoptosis of A549 cells. The expression of KCNQ1OT1 in LAD patients insensitive to paclitaxel was much higher than that in LAD patients sensitive to paclitaxel; the KCNQ1OT1 expression in A549/PA cells was also much higher than that in control A549 cells. The half maximal inhibitory concentration (IC50) of paclitaxel in A549/PA cells was depressed by KCNQ1OT1 knockdown, chemoresistance of A549/PA cells was inhibited significantly. KCNQ1OT1 knockdown also depressed the expression of multidrug resistance 1 (MDR1) protein in A549/PA cells. In summary, lncRNA KCNQ1OT1 was highly expressed in LAD and functioned as a potential oncogene to inhibit malignancy and chemoresistance of LAD cells, which might be a novel potential therapeutic target for LAD.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Shengjing Hospital, China Medical University, No. 36 Sanhao Street, Heping Area, Shenyang, 110004, Liaoning, China

    Kaiming Ren, Ran Xu, Jingshan Huang, Jungang Zhao & Wenjun Shi

Authors
  1. Kaiming Ren
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  2. Ran Xu
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  3. Jingshan Huang
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  4. Jungang Zhao
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  5. Wenjun Shi
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Correspondence to Wenjun Shi.

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Funding

This study was funded by the Doctoral Research Initiation Foundation of Liaoning Province (201601121).

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All authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with Ethics Committees of Dalian Medical University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Ren, K., Xu, R., Huang, J. et al. Knockdown of long non-coding RNA KCNQ1OT1 depressed chemoresistance to paclitaxel in lung adenocarcinoma. Cancer Chemother Pharmacol 80, 243–250 (2017). https://doi.org/10.1007/s00280-017-3356-z

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  • DOI: https://doi.org/10.1007/s00280-017-3356-z

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