Long non-coding RNA TNRC6C-AS1 promotes methylation of STK4 to inhibit thyroid carcinoma cell apoptosis and autophagy via Hippo signalling pathway

J Cell Mol Med. 2020 Jan;24(1):304-316. doi: 10.1111/jcmm.14728. Epub 2019 Oct 27.

Abstract

The role of long non-coding RNAs (lncRNAs) in thyroid carcinoma (TC), the most frequent endocrine malignancy, has been extensively examined. This study investigated effect of interaction among lncRNA TNRC6C-AS1, serine/threonine-protein kinase 4 (STK4) and Hippo signalling pathway on TC. Initially, lncRNA TNRC6C-AS1 expression in TC tissues was detected. To explore roles of lncRNA TNRC6C-AS1, STK4 and Hippo signalling pathway in TC progression, their expressions were altered. Interaction between lncRNA TNRC6C-AS1 and STK4, STK4 promoter methylation, or Hippo signalling pathway was verified. After that, a series of experiments were employed to evaluate in vitro ability of apoptosis, proliferation and autophagy of TC cells and in vivo tumorigenicity, and tumour growth of TC cells. lncRNA TNRC6C-AS1 was highly expressed while STK4 was poorly expressed in TC tissues. LncRNA TNRC6C-AS1 promoted the STK4 methylation and down-regulated STK4 expression, which further activated the Hippo signalling pathway. STK4 silencing was observed to promote the proliferation ability of TC cells, inhibit the apoptosis and autophagy abilities, as well as enhance the tumorigenicity and tumour growth. Moreover, the in vitro proliferation ability as well as the in vivo tumorigenicity and tumour growth of TC cells were inhibited after the blockade of Hippo signalling pathway, while the apoptosis and autophagy abilities were promoted. The results demonstrate that the lncRNA TNRC6C-AS1 increases STK4 promoter methylation to down-regulate STK4 expression, thereby promoting the development of TC through activation of Hippo signalling pathway. It highlights that lncRNA TNRC6C-AS1 may be a novel therapeutic target for the treatment of TC.

Keywords: Hippo signalling pathway; STK4; long non-coding RNA TNRC6C-AS1; methylation; thyroid carcinoma.

MeSH terms

  • Apoptosis / genetics*
  • Autophagy / genetics*
  • Base Sequence
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA Methylation / genetics*
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Models, Biological
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology*

Substances

  • RNA, Long Noncoding
  • STK4 protein, human
  • Hippo protein, human
  • Protein-Serine-Threonine Kinases