BRAF-Activated Long Noncoding RNA Modulates Papillary Thyroid Carcinoma Cell Proliferation through Regulating Thyroid Stimulating Hormone Receptor

Cancer Res Treat. 2016 Apr;48(2):698-707. doi: 10.4143/crt.2015.118. Epub 2015 Aug 12.

Abstract

Purpose: The importance of long noncoding RNAs (lncRNAs) in tumorigenesis has recently been demonstrated. However, the role of lncRNAs in development of thyroid cancer remains largely unknown.

Materials and methods: Using quantitative reverse transcription polymerase chain reaction, expression of three lncRNAs, including BRAF-activated long noncoding RNA (BANCR), papillary thyroid cancer susceptibility candidate 3 (PTCSC3), and noncoding RNA associated with mitogen-activated protein kinase pathway and growth arrest (NAMA), was investigated in the current study.

Results: Of the three lncRNAs (BANCR, PTCSC3, and NAMA), expression of BANCR was significantly up-regulated while PTCSC3 and NAMA were significantly down-regulated in papillary thyroid carcinoma (PTC) compared to that in normal tissue. BANCR-knockdown in a PTC-derived cell line (IHH-4) resulted in significant suppression of thyroid stimulating hormone receptor (TSHR). BANCR-knockdown also led to inhibition of cell growth and cell cycle arrest at G0/G1 phase through down-regulation of cyclin D1. In addition, BANCR was enriched by polycomb enhancer of zeste homolog 2 (EZH2), and silencing BANCR led to decreased chromatin recruitment of EZH2, which resulted significantly reduced expression of TSHR.

Conclusion: These findings indicate that BANCR may contribute to the tumorigenesis of PTC through regulation of cyclin D1 and TSHR.

Keywords: BRAF-activated long noncoding RNA; Long noncoding RNA; Thyroid neoplasms.

MeSH terms

  • Carcinoma, Papillary* / genetics
  • Carcinoma, Papillary* / metabolism
  • Carcinoma, Papillary* / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Proto-Oncogene Proteins B-raf*
  • RNA, Long Noncoding
  • Receptors, Thyrotropin / metabolism*
  • Thyroid Neoplasms* / genetics
  • Thyroid Neoplasms* / metabolism
  • Thyroid Neoplasms* / pathology

Substances

  • RNA, Long Noncoding
  • Receptors, Thyrotropin
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf