Long non-coding RNA SNHG1 regulates zinc finger E-box binding homeobox 1 expression by interacting with TAp63 and promotes cell metastasis and invasion in Lung squamous cell carcinoma

Biomed Pharmacother. 2017 Jun:90:650-658. doi: 10.1016/j.biopha.2017.03.104. Epub 2017 Apr 14.

Abstract

The long non-coding RNAs (lncRNAs) have been recently shown to participate in the progression of a variety of cancers. However, the biological role of lncRNAs and the underlying mechanisms in Lung squamous cell carcinoma (SCC) or lung adenocarcinoma (AD) remain unclear. Herein, we investigated expression of 5 lncRNAS (SNHG1, NCBP2-AS2, LINC01206, SOX2-OT and LINC01419) in SCC and AD tissues. SNHG1 was one of over-expressed lncRNAs in SCC tissues. Knockdown of SNHG1 significantly inhibited the proliferation, metastasis, invasive ability and induced apoptosis of SCC cells. Moreover, SNHG1 affected the expression of zinc finger E-box binding homeobox 1(ZEB1), which has also been observed to be up-regulated in SCC and to promote cell metastasis and invasion. Rather than direct interaction, SNHG1 regulated ZEB1expression by suppressing the activity of p63 TA isoform (TAp63), which is a repressor of ZEB1 and physically associates with SNHG1. Furthermore, SNHG1 promoted ZEB1 expression and promoted cell proliferation, metastasis, invasive but inhibited apoptosis of SCC cells via the TAp63/ZEB1 pathway. Taken together, our findings suggested that SNHG1 might play an oncogenic role in SCC through ZEB1 signaling pathway by inhibiting TAp63 and might serve as a valuable prognostic biomarker and therapeutic target for SCC patients.

Keywords: Lung cancer; SNHG1; TAp63; ZEB1.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Aged
  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / pathology
  • RNA, Long Noncoding / genetics*
  • Signal Transduction / genetics
  • Transcription Factors / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Up-Regulation / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / genetics*

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • long non-coding RNA SNHG1, human