miR-1908 Overexpression Inhibits Proliferation, Changing Akt Activity and p53 Expression in Hypoxic NSCLC Cells

Oncol Res. 2016;24(1):9-15. doi: 10.3727/096504016X14570992647168.

Abstract

The ribosomal protein (RP)-p53 pathway has been shown to play a key role in apoptosis and senescence of cancer cells. miR-1908 is a newly found miRNA that was reported to have prognostic potential in melanoma. However, its role and mechanism in the progression of non-small cell lung cancer (NSCLC) are largely unknown. In this study, we found that expression of miR-1908 was significantly downregulated in human NSCLC cell lines, including SK-MES-1, A549, and NCI-H460. Then the role of miR-1908 in NSCLC cell proliferation was explored. The miR-1908 mimic was transfected into NSCLC cell lines, and their proliferation was detected. MTT and Cell Titer-Blue H analyses showed that the cell proliferation was notably reduced by the miR-1908 mimic transfection. Moreover, we found the RP-p53 pathway was activated by miR-1908 mimic. Moreover, the miR-1908 inhibitor transfection had a completely opposite effect on the NSCLC cell proliferation than that of miR-1908 mimic. To explore the underlying mechanism of that, TargetScan bioinformatics server and 3'-UTR luciferase reporter assay were applied to identify the targets of miR-1908. Our results showed that AKT1 substrate 1 (AKT1S1), a newly proven suppressor of the RP-p53 pathway, was a target of miR-1908, suggesting a probable mechanism for miR-191 suppressing NSCLC cell proliferation. Our findings provide a novel molecular target for the regulation of NSCLC cell proliferation.

MeSH terms

  • A549 Cells
  • Adaptor Proteins, Signal Transducing / genetics
  • Apoptosis / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Hypoxia / genetics*
  • Lung Neoplasms / genetics*
  • MicroRNAs / genetics*
  • Proto-Oncogene Proteins c-akt / genetics*
  • Transfection / methods
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • AKT1S1 protein, human
  • Adaptor Proteins, Signal Transducing
  • MIRN1908 microRNA, human
  • MicroRNAs
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-akt