MicroRNA-1179 suppresses cell growth and invasion by targeting sperm-associated antigen 5-mediated Akt signaling in human non-small cell lung cancer

Biochem Biophys Res Commun. 2018 Sep 26;504(1):164-170. doi: 10.1016/j.bbrc.2018.08.149. Epub 2018 Sep 1.

Abstract

Accumulating evidence has identified microRNA-1179 (miR-1179) as a novel cancer-related miRNA that is dysregulated in multiple cancers and plays an important role in regulating cancer development and progression. However, little is known about the role of miR-1179 in non-small cell lung cancer (NSCLC). Thus, in the present study, we aimed to investigate the potential biological function and regulatory mechanism of miR-1179 in NSCLC. The results showed that decreased expression of miR-1179 expression was frequently detected in primary NSCLC tissues and cell lines. Overexpression of miR-1179 suppressed the growth and invasion of NSCLC cells in vitro while its inhibition promoted the opposite effect. Sperm-associated antigen 5 (SPAG5) was an identified as a target gene of miR-1179. Moreover, SPAG5 expression was increased in NSCLC cells and showed an inverse correlation with miR-1179 in NSCLC specimens. SPAG5 knockdown inhibited the growth and invasion of NSCLC cells, results that simulated a similar effect to miR-1179 overexpression. Mechanistic investigations showed that miR-1179 overexpression or SPAG5 knockdown significantly downregulated the activation of Akt signaling. Additionally, SPAG5 overexpression partially reversed the antitumor effect of miR-1179. Overall, our results demonstrated that miR-1179 inhibited the growth and invasion of NSCLC cells by targeting SPAG5 and inhibiting Akt, findings that highlight the importance of the miR-1179/SPAG5/Akt axis in the progression of NSCCL.

Keywords: Akt; Non-small cell lung cancer; SPAG5; miR-1179.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction*

Substances

  • Cell Cycle Proteins
  • MIRN1179 microRNA, human
  • MicroRNAs
  • SPAG5 protein, human
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt