LncRNA TDRG1 promotes the metastasis of NSCLC cell through regulating miR-873-5p/ZEB1 axis

J Cell Biochem. 2021 Sep;122(9):969-982. doi: 10.1002/jcb.29559. Epub 2019 Nov 19.

Abstract

Long noncoding RNAs (lncRNAs) are dysregulated in various malignancies and involved in the growth and aggressive phenotypes of cancer cells. Previous studies indicate that lncRNA testis development related 1 (TDRG1) plays critical roles in the development of several malignancies. Nevertheless, the molecular mechanism underlying TDRG1 contributes to non-small cell lung cancer (NSCLC) remains elusive. Here, we demonstrate that TDRG1 is significantly overregulated in NSCLC tissues and cell lines. Knockdown of TDRG1 inhibits the proliferation and metastatic-related traits of NSCLC cell in vitro whereas overexpression of TDRG1 causes opposite results. In addition, TDRG1 silencing inhibits the growth and metastatic ability of NSCLC cell in vivo as demonstrated by xenograft tumor model and lung metastasis model. The binding capacity of TDRG1 with miR-873-5p is demonstrated by bioinformatics prediction tool and luciferase reporter gene assay. Additional, the rescue experiments indicate that TDRG1 interacts with miR-873-5p and its expression is positively associated with the target of miR-873-5p, zinc finger e-box binding homeobox 1 (ZEB1). Altogether, lncRNA TDRG1 facilitates the progression of NSCLC via interacting with miR-873-5p and positively regulates the expression of ZEB1.

Keywords: NSCLC; TDRG1; ZEB1; metastasis; miR-873-5p.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / genetics
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / metabolism
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

  • MicroRNAs
  • MIRN873 microRNA, human
  • RNA, Long Noncoding
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • TDRG1 long non-coding RNA, human