Positive feedback loop of lncRNA LINC01296/miR-598/Twist1 promotes non-small cell lung cancer tumorigenesis

J Cell Physiol. 2019 Apr;234(4):4563-4571. doi: 10.1002/jcp.27235. Epub 2018 Sep 21.

Abstract

Emerging evidence has illustrated the vital roles of long noncoding RNAs (lncRNAs) in human cancers. However, the role of lncRNAs in non-small cell lung cancer (NSCLC) is still elusive and poorly understood. In the current study, our team conducted extensive experiments to identify the role of long intergenic nonprotein coding (LINC01296) on NSCLC tumorigenesis. The results illustrated that the elevated LINC01296 expression in NSCLC tissue specimens and cell lines were closely correlated with the poor prognosis of patients with NSCLC. Functional studies revealed that LINC01296 knockdown silenced by small interfering RNAs inhibited proliferation, accelerated apoptosis in vitro, and impaired tumor growth in vivo. Mechanical studies showed that INC01296 harbored miR-598, acting as a microRNA "sponge." Besides, miR-598 targeted the 3'-UTR of Twist1. Interestingly, transcription factor Twist1 could bind with the promoter of INC01296 and activate its transcriptional level. In summary, we conclude that INC01296/miR-598/Twist1 constitutes a positive feedback loop to promote the tumorigenesis of NSCLC, providing a novel insight and a valuable therapeutic strategy.

Keywords: long intergenic nonprotein coding RNA 01296 (LINC01296); Twist1; feedback loop; miR-598; non-small cell lung cancer (NSCLC).

MeSH terms

  • 3' Untranslated Regions
  • A549 Cells
  • Animals
  • Apoptosis
  • Binding Sites
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Proliferation
  • Feedback, Physiological
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Tumor Burden
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism*

Substances

  • 3' Untranslated Regions
  • LINC01296 long non-coding RNA, human
  • MIRN-598 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Long Noncoding
  • TWIST1 protein, human
  • Twist-Related Protein 1