MicroRNA-1204 promotes cell proliferation by regulating PITX1 in non-small-cell lung cancer

Cell Biol Int. 2019 Mar;43(3):253-264. doi: 10.1002/cbin.11083. Epub 2019 Jan 28.

Abstract

MicroRNA-1204 (miR-1204), a member of the PVT1 region, may improve B cell differentiation and metastasis in breast cancer. However, the role of miR-1204 in non-small-cell lung cancer (NSCLC) and its mechanism remain unclear. The GEO public database was first employed to find differentially expressed genes. The expression level of miR-1204 in patient tissues and NSCLC cell lines was determined using qRT-PCR. Cell proliferation assays were performed to investigate the impact of miR-1204 on cell growth. Bioinformatics analysis and dual-luciferase reporter assays were conducted to find potential target genes. Finally, we performed in vivo experiments to identify the effect of miR-1204 on tumor formation in nude mice. It was first found that miR-1204 was overexpressed in NSCLC tissues and cells. miR-1204 increased the proliferation of NSCLC cells and reduced cell cycle arrest in vitro. PITX1 (paired like homeodomain 1) was found as a potential target gene. In addition, PITX1 was also found to be low in expression in NSCLC tissues and cells. To show that PITX1 reversed the function of miR-1204 in promoting proliferation, confirmatory experiments were performed. Moreover, high miR-1204 and low PITX1 expression was highly correlated with tumor size, lymph node metastasis, and the TNM stage in patients diagnosed with NSCLC. Our results suggested that upregulated miR-1204 in NSCLC is associated with NSCLC progression and promotes NSCLC cell proliferation by downregulating PITX1. miR-1204 may act as a poor prognostic factor and a potential therapeutic target for NSCLC.

Keywords: PITX1; microRNA-1204; non-small-cell lung cancer; proliferation.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Paired Box Transcription Factors / genetics*
  • Paired Box Transcription Factors / metabolism
  • Up-Regulation / genetics
  • Xenograft Model Antitumor Assays

Substances

  • 3' Untranslated Regions
  • MIRN-1204 microRNA, human
  • MicroRNAs
  • Paired Box Transcription Factors
  • homeobox protein PITX1