MiR-504 inhibits cell proliferation and invasion by targeting LOXL2 in non small cell lung cancer

Biomed Pharmacother. 2018 Jan:97:1289-1295. doi: 10.1016/j.biopha.2017.11.005. Epub 2017 Dec 14.

Abstract

Background: MicroRNAs (miRNAs) play crucial roles in tumor initiation and development. The aim of the study was to explore the clinicopathological role and functional effects of miR-504 in non small cell lung cancer (NSCLC).

Methods: Quantitative reverse transcription polymerase chain reaction (QRT-PCR) was applied to detect the expression of miR-504 in 55 cases of NSCLC tissues and matched adjacent normal tissues in NSCLC patients. MTT, colony formation and transwell invasion assays were performed to evaluate the effects of miR-504 on cell proliferation and invasion, respectively. Dual luciferase reporter assay was used to verify that LOXL2 was a direct target of miR-504. QRT-PCR and western blot analysis were performed to analyze mRNA and protein expression.

Results: In the study, we demonstrated that miR-504 was notably downregulated in NSCLC tissues compared with adjacent normal tissues. Lower miR-504 expression positively correlated with lymph node metastasis and advanced TNM stage in patients. Furthermore, upregulation of miR-504 significantly inhibited cell proliferation, cell invasion and EMT process of NSCLC. QRT-PCR, western blot and luciferase reporter assays confirmed that miR-504 could bind to LOXL2 3'UTR region and regulate its expression. Moreover, ectopic expression of LOXL2 could rescue the inhibiting effects on cell proliferation and invasion induced by miR-504 in NSCLC cells.

Conclusions: Our results indicated that miR-504 functioned as a tumor suppressor in NSCLC and may serve as a target of NSCLC treatment.

Keywords: Epithelial-mesenchymal transition; LOXL2; MiR-504; Non small cell lung cancer.

MeSH terms

  • Amino Acid Oxidoreductases / genetics*
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Proliferation / genetics
  • Down-Regulation
  • Female
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation / genetics

Substances

  • MIRN504 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Amino Acid Oxidoreductases
  • LOXL2 protein, human