Downregulation of LINC00665 suppresses the progression of lung adenocarcinoma via regulating miR-181c-5p/ZIC2 axis

Aging (Albany NY). 2021 Jul 7;13(13):17499-17515. doi: 10.18632/aging.203240. Epub 2021 Jul 7.

Abstract

Long non-coding RNA (lncRNA) LINC00665 was demonstrated to be upregulated in lung adenocarcinoma (LUAD) and target miR-181c-5p. ZIC2, which is upregulated in LUAD, serves as a putative target of miR-181c-5p. In this study, we aimed to reveal whether LINC00665 regulates miR-181c-5p/ZIC2 axis to promote LUAD progression. The results showed that LINC00665, HOXA1, ZIC2, and HOXA11 levels were increased in LUAD tissues, while miR-181c-5p level was decreased when compared to the adjacent normal tissues. High expression levels of LINC00665, ZIC2, HOXA1 and HOXA11, and low expression of miR-181c-5p were closely linked to poor prognosis of LUAD patients. Knockdown of LINC00665 induced obvious inhibitions in cell viability, clone formation, invasion and tumorigenesis in LUAD cells, whereas miR-181c-5p downregulation significantly neutralized these effects. In addition, downregulation of ZIC2 obviously reversed the enhancements of cell viability, clone formation, invasion and tumorigenesis induced by miR-181c-5p knockdown. In summary, the present study reveals that silencing of LINC00665 suppresses LUAD progression through targeting miR-181c-5p/ZIC2 axis.

Keywords: HOXA1; HOXA11; LINC00665; ZIC2; miR-181c-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Animals
  • Cell Line, Tumor
  • Cell Survival
  • Computational Biology
  • Disease Progression
  • Down-Regulation
  • Gene Knockdown Techniques
  • Homeobox A1 Protein
  • Homeodomain Proteins / genetics
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Nuclear Proteins / genetics*
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Transcription Factors / genetics*
  • Tumor Stem Cell Assay
  • Xenograft Model Antitumor Assays

Substances

  • Homeodomain Proteins
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Long Noncoding
  • Transcription Factors
  • Homeobox A1 Protein
  • HOXA11 protein, human
  • MIRN-181 microRNA, human
  • ZIC2 protein, human