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Downregulation of microRNA-21 expression restrains non-small cell lung cancer cell proliferation and migration through upregulation of programmed cell death 4

Cancer Gene Therapy volume 22, pages 23–29 (2015)Cite this article

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Abstract

Preliminary studies showed that miR-21 is overexpressed in some human cancers. However, the role of miR-21 in cancer is still unclear and even controversial. Our purpose was to investigate the biological effects of miR-21 on A549 non-small cell lung cancer (NSCLC) cells and the underlying mechanisms of those effects. The expression of miR-21 was quantified in serum samples from patients with NSCLC. A549 cells were transfected with miR-NC-sponge or miR-21-sponge only, or with miR-21-sponge plus PDCD4 small-interfering RNA (siRNA). The expression of miR-21 and PDCD4 mRNA in transfected cells was quantified by real-time polymerase chain reaction and the expression of PDCD4 protein by Western blot. Cell proliferation, apoptosis, migration, and invasion assays were performed to determine the biological effects of miR-21 expression and PDCD4 inhibition. miR-21 was overexpressed in serum from patients with NSCLC. Reduced miR-21 expression was observed following transfection with miR-21-sponge in A549 NSCLC cells. Co-transfection of miR-21-sponge with PDCD4 siRNA upregulated miR-21 expression in these cells. PDCD4 mRNA and protein levels were increased 2.14-fold and 2.16-fold, respectively, following inhibition of miR-21 expression. Inhibition of miR-21 expression following transfection of miR-21-sponge reduced cell proliferation, migration, and invasion of A549 cells. Depletion of PDCD4 by siRNA transfection reversed the reduction of cell proliferation, migration, and invasion induced by inhibition of miR-21 in A549 cells. It indicates that miR-21 is highly expressed in patients with NSCLC and inhibition of miR-21 expression reduces proliferation, migration, and invasion of A549 cells by upregulating PDCD4 expression. Modulation of miR-21 or PDCD4 expression may provide a potentially novel therapeutic approach for NSCLC.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (81170257) and Zhejiang Provincial Natural Science Foundation (Y2110513).

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Authors and Affiliations

  1. Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China

    Y Yang, H Meng, Q Peng, X Yang, R Gan, L Zhao & J Lu

  2. Department of Laboratory Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

    Z Chen

  3. Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China

    J Lu

  4. Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou, Zhejiang, China

    J Lu

  5. Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA

    Q H Meng

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  1. Y Yang
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Correspondence to J Lu or Q H Meng.

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Yang, Y., Meng, H., Peng, Q. et al. Downregulation of microRNA-21 expression restrains non-small cell lung cancer cell proliferation and migration through upregulation of programmed cell death 4. Cancer Gene Ther 22, 23–29 (2015). https://doi.org/10.1038/cgt.2014.66

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  • DOI: https://doi.org/10.1038/cgt.2014.66

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