ΜicroRNA‑889 plays a suppressive role in cell proliferation and invasion by directly targeting TAB1 in non‑small cell lung cancer

Mol Med Rep. 2019 Jul;20(1):261-269. doi: 10.3892/mmr.2019.10245. Epub 2019 May 15.

Abstract

MicroRNAs (miRNAs) are frequently reported to be aberrantly expressed in non‑small cell lung cancer (NSCLC) and are closely associated with aggressive tumor phenotypes. Hence, identification of cancer‑related miRNAs in NSCLC may be helpful for improving the cure rate of NSCLC treatments. miR‑889 has been demonstrated to be a novel cancer‑associated miRNA that is aberrantly expressed and plays an important role in esophageal squamous cell carcinoma and hepatocellular carcinoma. However, the exact functions and precise molecular mechanisms through which miR‑889 affects NSCLC progression are still unknown. In the present study, we report for the first time that miR‑889 expression is low in NSCLC tissues and cell lines. Clinically, low miR‑889 expression was found to be correlated with the TNM stage and distant metastasis in NSCLC patients. Functionally, miR‑889 overexpression suppressed the proliferation and invasiveness of NSCLC cells in vitro and decreased NSCLC xenograft tumor growth in mice. Furthermore, TGF‑β‑activated kinase 1‑binding protein 1 (TAB1) was confirmed as a direct target gene of miR‑889 in NSCLC cells. TAB1 was revealed to be overexpressed in NSCLC tissue samples and was inversely correlated with miR‑889 levels. Moreover, a TAB1 knockdown had effects similar to that of miR‑889 overexpression, whereas restoration of TAB1 expression counteracted the actions of miR‑889 in NSCLC cells. Overall, the present results indicated that miR‑889 inhibits the aggressive behaviors of NSCLC by directly targeting TAB1 mRNA, thus highlighting the importance of the miR‑889/TAB1 pathway in the malignant progression of NSCLC.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Heterografts
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • RNA Interference

Substances

  • Adaptor Proteins, Signal Transducing
  • MicroRNAs
  • TAB1 protein, human