miR-455-3p serves as prognostic factor and regulates the proliferation and migration of non-small cell lung cancer through targeting HOXB5

Biochem Biophys Res Commun. 2018 Jan 1;495(1):1074-1080. doi: 10.1016/j.bbrc.2017.11.123. Epub 2017 Nov 21.

Abstract

MicroRNAs (miRs) have been reported to play significantly roles in the initiation and progression of human cancers. miR-455-3p has been recently found could function as tumor suppressor in various human cancers. However, its expression and biological role in non-small cell lung cancer (NSCLC) remains elusive. In this study, we found miR-455-3p was markedly downregulated in NSCLC tissues and cell lines. Chi-square test to analyze the correlations between miR-455-3p expression and clinicopathological features revealed that miR-455-3p expression was correlated with poorly differentiated cancer and advanced tumor stage (P < 0.05). Kaplan-Meier curve revealed that low expression of miR-455-3p was correlated with shorter 5-year survival time (P = 0.029). Univariate and multivariate analyses identified low miR-455-3p expression was an unfavorable prognostic factor for overall survival. Gain-of-function and loss-of-function studies revealed that miR-455-3p inhibits cell proliferation and migration in vitro. Computer algorithm and dual-luciferase reporter assay revealed that miR-455-3p directly targets and suppresses HOXB5 in NSCLC. Further studies demonstrated that knockdown of HOXB5 attenuated the effect of miR-455-3p downregulation on cell proliferation and migration. Taken together, our results for the first time suggested that miR-455-3p was downregulated in NSCLC and was correlated with the poor prognosis of NSCLC patients. Also, miR-455-3p functions as tumor suppressor by directly targeting HOXB5 in NSCLC progression and may be used as a potential target for NSCLC treatment.

Keywords: HOXB5; Migration; Non-small cell lung cancer; Proliferation; miR-455-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Movement
  • Cell Proliferation
  • China / epidemiology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / metabolism*
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Prevalence
  • Prognosis
  • Protein Binding
  • Risk Factors
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • HOXB5 protein, human
  • Homeodomain Proteins
  • MIRN455 microRNA, human
  • MicroRNAs