Overexpression of miR-4286 is an unfavorable prognostic marker in individuals with non-small cell lung cancer

J Cell Biochem. 2019 Oct;120(10):17573-17583. doi: 10.1002/jcb.29024. Epub 2019 May 20.

Abstract

Non-small cell lung cancer (NSCLC) is still an unresolved source of tumor-related death internationally. Current studies have discovered that microRNAs (miRNAs) are associated with diverse cancers development, including NSCLC. Our paper focused on the functional character of miR-4286 in NSCLC. miR-4286 level in 68 cases of NSCLC tissues, matched neighboring nontumor tissues and different cancer cell lines were inspected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The connection concerning miR-4286 expression and clinicopathological features of patients with NSCLC were further determined. After knockdown or overexpression of miR-4286, cell viability, cell cycle, and/or apoptotic cells were examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assay, respectively. Moreover, the cell cycle- and apoptosis-related proteins were estimated by qRT-PCR and Western blot. In comparison with the matched nontumor tissues, miR-4286 was significantly enhanced in lung malignancy tissues and different cell lines. miR-4286 expression was related with the tumor-node-metastasis stage, lymphatic metastasis, and distant metastasis. Cell viability was ominously weakened by suppression of miR-4286 in A549 cells, whereas was statistically upregulated by overexpression of miR-4286 in NCI-H1299 cells. Additionally, we detected that suppression of miR-4286 tempted cell cycle arrest in G1 stage and fortified apoptosis in A549 cells. Runx3 was recognized as one target gene of miR-4286, and the impacts of suppression of miR-4286 on cell viability and apoptosis were through regulation of Runt-related transcription factor 3. Our study suggests that miR-4286 overexpression represents a tumor promoter role in NSCLC cells.

Keywords: Runx3; cell apoptosis; cell viability; miR-4286; non-small cell lung cancer.

MeSH terms

  • A549 Cells
  • Adult
  • Aged
  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / epidemiology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Core Binding Factor Alpha 3 Subunit / genetics*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Prognosis*

Substances

  • Biomarkers, Tumor
  • Core Binding Factor Alpha 3 Subunit
  • MIRN-4286 microRNA, human
  • MicroRNAs
  • Runx3 protein, human