miR-99a regulates ROS-mediated invasion and migration of lung adenocarcinoma cells by targeting NOX4

  • Authors:
    • Mei Sun
    • Shunming Hong
    • Wenhan Li
    • Pengfei Wang
    • Jinqiang You
    • Xuebin Zhang
    • Fan Tang
    • Ping Wang
    • Chunzhi Zhang
  • View Affiliations

  • Published online on: March 11, 2016     https://doi.org/10.3892/or.2016.4672
  • Pages: 2755-2766
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Abstract

miR-99a is frequently downregulated in various types of human malignancies including lung adenocarcinoma. Recent studies have reported that miR-99a regulates cell growth and cell cycle progression by targeting mTOR, AKT1 and FGFR3. However, the underlying mechanisms involved in the modulation of invasion and migration by miR-99a remain elusive. In this study, we analyzed the relationship between the expression of miR-99a and clinical stage or metastasis in 90 matched lung adenocarcinoma and adjacent non-tumor lung tissues. Downregulation of miR-99a was significantly associated with advanced stage and tumor metastasis in lung adenocarcinoma patients, and it was found to be a poor prognostic factor in lung adenocarcinoma. Furthermore, functional experiments found that overexpression of miR-99a inhibited the proliferation, migration and invasion of lung adenocarcinoma A549 and Calu3 cells in vitro. We then identified NOX4 as a target gene of miR-99a and NOX4 mediated the inhibition of invasion and migration of lung adenocarcinoma cells by miR-99a. By targeting NOX4-mediated ROS production, miR-99a regulated the invasion and migration of lung adenocarcinoma cells. Moreover, overexpression of miR-99a significantly inhibited tumor growth in vivo. Immunohistochemical staining analysis of the mouse tumor tissues revealed that NOX4 levels were downregulated in the miR-99a treatment group, confirming the in vitro data of NOX4 as a direct target gene of miR-99a. Taken together, these data indicate for the first time that miR-99a directly regulates the invasion and migration in lung adenocarcinoma by targeting NOX4 and that overexpression of miR-99a may become a therapeutic strategy for lung adenocarcinoma.
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May-2016
Volume 35 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Sun M, Hong S, Li W, Wang P, You J, Zhang X, Tang F, Wang P and Zhang C: miR-99a regulates ROS-mediated invasion and migration of lung adenocarcinoma cells by targeting NOX4. Oncol Rep 35: 2755-2766, 2016.
APA
Sun, M., Hong, S., Li, W., Wang, P., You, J., Zhang, X. ... Zhang, C. (2016). miR-99a regulates ROS-mediated invasion and migration of lung adenocarcinoma cells by targeting NOX4. Oncology Reports, 35, 2755-2766. https://doi.org/10.3892/or.2016.4672
MLA
Sun, M., Hong, S., Li, W., Wang, P., You, J., Zhang, X., Tang, F., Wang, P., Zhang, C."miR-99a regulates ROS-mediated invasion and migration of lung adenocarcinoma cells by targeting NOX4". Oncology Reports 35.5 (2016): 2755-2766.
Chicago
Sun, M., Hong, S., Li, W., Wang, P., You, J., Zhang, X., Tang, F., Wang, P., Zhang, C."miR-99a regulates ROS-mediated invasion and migration of lung adenocarcinoma cells by targeting NOX4". Oncology Reports 35, no. 5 (2016): 2755-2766. https://doi.org/10.3892/or.2016.4672