miR-1297 Promotes Cell Proliferation of Non-Small Cell Lung Cancer Cells: Involving in PTEN/Akt/Skp2 Signaling Pathway

DNA Cell Biol. 2017 Nov;36(11):976-982. doi: 10.1089/dna.2017.3886. Epub 2017 Sep 5.

Abstract

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a lipid and protein phosphatase and possesses an antitumor effect in lung cancers. miRNAs are reportedly abnormally expressed in human lung cancers. However, whether miRNA contributes to PTEN expression in non-small cell lung cancers (NSCLCs) has not been clearly clarified. In the present study, we found that miR-1297 probably binds with 3'UTR sequence of PTEN and negatively regulated the levels of PTEN in NSCLC cells. First, the expression levels of PTEN and Skp2 were detected by western blotting in NSCLC specimens and paired normal tissue specimens. The results showed that decreased levels of PTEN were detected in NSCLC tissues, compared with paired control tissues (**p < 0.01). The expression levels of PTEN were conversely correlated with the levels of Skp2 in clinical NSCLC specimens and NSCLC cell line. Transfection with miR-1297 mimic significantly promoted cell viability of A549 cells and NCI-H460 cells by downregulating the level of PTEN and upregulating the expression of Skp2. Interestingly, knockdown of Skp2 did not affect the expression of PTEN in A549 cells. Thus, miR-1297 might work as an oncogene by regulating PTEN/Akt/Skp2 signaling pathway in NSCLC cells. PTEN and Skp2 might be the potential targets in the clinical therapy of lung cancers.

Keywords: NSCLC; PTEN; Skp2; miR-1297.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Case-Control Studies
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • MicroRNAs / genetics*
  • PTEN Phosphohydrolase / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • S-Phase Kinase-Associated Proteins / metabolism*
  • Signal Transduction
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • MIRN1297 microRNA, human
  • MicroRNAs
  • S-Phase Kinase-Associated Proteins
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human