Open Access

MicroRNA‑101 suppresses progression of lung cancer through the PTEN/AKT signaling pathway by targeting DNA methyltransferase 3A

  • Authors:
    • Lumin Wang
    • Jiayi Yao
    • Hongfei Sun
    • Kang He
    • Dongdong Tong
    • Tusheng Song
    • Chen Huang
  • View Affiliations

  • Published online on: November 23, 2016     https://doi.org/10.3892/ol.2016.5423
  • Pages: 329-338
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It is well established that transcriptional silencing of critical tumor suppressor genes by DNA methylation is a fundamental process in the initiation of lung cancer. However, the involvement of microRNAs (miRNAs) in restoring abnormal DNA methylation patterns in lung cancer is not well understood. Therefore, and since miRNA‑101 is complementary to the 3'‑untranslated region of DNA methyltransferase 3A (DNMT3A), we investigated whether miRNA‑101 could restore normal DNA methylation patterns in lung cancer cell lines. Bioinformatics has indicated that DNMT3A is a major target of miR‑101. In addition, the overexpression of miR‑101 downregulates DNMT3A. Using a methylation‑specific polymerase chain reaction assay, we demonstrated that methylation of the phosphatase and tensin homolog (PTEN) promoter was reduced in A549 cells transfected with miR‑101, but not in the transfected control. Furthermore, overexpression of miR‑101 and silencing of DNMT3A suppressed lung cell proliferation and S/G2 transition, and increased apoptosis through the PTEN/AKT pathway in vitro. Furthermore, we observed the opposite phenomenon in A549 cells transfected with a miR‑101 inhibitor. Subsequent investigation revealed that overexpression of miR‑101 significantly inhibited the tumorigenicity of A549 cells in a nude mouse xenograft model. These results demonstrate that miR‑101 affects lung cancer progression through the PTEN/AKT signaling pathway by targeting DNMT3A in lung cells, suggesting that miR‑101 may be a novel potential therapeutic strategy in lung cancer treatment.
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January-2017
Volume 13 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Wang L, Yao J, Sun H, He K, Tong D, Song T and Huang C: MicroRNA‑101 suppresses progression of lung cancer through the PTEN/AKT signaling pathway by targeting DNA methyltransferase 3A. Oncol Lett 13: 329-338, 2017
APA
Wang, L., Yao, J., Sun, H., He, K., Tong, D., Song, T., & Huang, C. (2017). MicroRNA‑101 suppresses progression of lung cancer through the PTEN/AKT signaling pathway by targeting DNA methyltransferase 3A. Oncology Letters, 13, 329-338. https://doi.org/10.3892/ol.2016.5423
MLA
Wang, L., Yao, J., Sun, H., He, K., Tong, D., Song, T., Huang, C."MicroRNA‑101 suppresses progression of lung cancer through the PTEN/AKT signaling pathway by targeting DNA methyltransferase 3A". Oncology Letters 13.1 (2017): 329-338.
Chicago
Wang, L., Yao, J., Sun, H., He, K., Tong, D., Song, T., Huang, C."MicroRNA‑101 suppresses progression of lung cancer through the PTEN/AKT signaling pathway by targeting DNA methyltransferase 3A". Oncology Letters 13, no. 1 (2017): 329-338. https://doi.org/10.3892/ol.2016.5423