LncRNA TUG1 contributes to the tumorigenesis of lung adenocarcinoma by regulating miR-138-5p-HIF1A axis

Int J Immunopathol Pharmacol. 2021 Jan-Dec:35:20587384211048265. doi: 10.1177/20587384211048265.

Abstract

Introduction: Increasing evidence indicates that lncRNA TUG1 represents an oncogenic factor in cancer. But, the mechanisms by which lncRNA TUG1 contributes to lung adenocarcinoma (LAC) remain undocumented.

Methods: The relationship between lncRNA TUG1/miR-138-5p expression and clinical outcomes in patients with LAC was indicated by qPCR, FISH, and TCGA cohort. Gain- or loss-of-function experiments and in vivo tumorigenesis were used to assess the role of lncRNA TUG1 in LAC. The interplay between TUG1 and miR-138-5p was validated by luciferase gene report and RIP assays. qPCR and Western blot analyses were used to investigate the effects of TUG1 on miR-138-5p/HIF1A axis in LAC cells.

Results: We found that upregulation of TUG1 or downregulation of miR-138-5p was associated with lymph node or distant metastasis and indicated a poor survival in LAC. Reduced expression of TUG1 restrained the growth of LAC cells, while restored expression of TUG1 had the opposite effects. TUG1 was identified to negatively regulate miR-138-5p expression, and miR-138-5p reversed TUG1-induced cell proliferation by targeting HIF1A. Elevated expression of HIF1A predicted a poor survival in LAC.

Conclusion: Our findings demonstrate that lncRNA TUG1 promotes the growth of LAC by regulating miR-138-5p-HIF1A axis.

Keywords: growth; invasion; lncRNA TUG1; lung adenocarcinoma; miR-138-5p.

MeSH terms

  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / mortality
  • Adenocarcinoma of Lung / pathology
  • Animals
  • Carcinogenesis
  • Cell Line, Tumor
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs*
  • RNA, Long Noncoding*

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN138 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TUG1 long noncoding RNA, human