Long noncoding RNA PVT1 modulates thyroid cancer cell proliferation by recruiting EZH2 and regulating thyroid-stimulating hormone receptor (TSHR)

Tumour Biol. 2016 Mar;37(3):3105-13. doi: 10.1007/s13277-015-4149-9. Epub 2015 Oct 1.

Abstract

The purposes of this study were to investigate the potential roles of long noncoding RNA (lncRNA) PVT1 in thyroid cancer cell proliferation and to explore their possible mechanisms. A total of 84 patients who were diagnosed as having thyroid cancer (papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and anaplastic thyroid carcinoma (ATC)) in Renji Hospital were enrolled in this study. Expressions of lncRNA PVT1 in thyroid cancer tissues and cell lines (IHH-4, FTC-133, and 8505C) were analyzed using RT-polymerase chain reaction (PCR) and western blotting analysis. The effects of lncRNA PVT1 expression on thyroid cancer cell proliferation and cell cycle were analyzed using flow cytometry. Furthermore, the effects of lncRNA expression on thyroid-stimulating hormone receptor (TSHR) expression and polycomb enhancer of zeste homolog 2 (EZH2) were also analyzed using RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay, respectively. Compared to the controls, lncRNA PVT1 was significantly up-regulated in thyroid tissues, as well as in three kinds of tumor cell lines (P < 0.05). Silenced PVT1 significantly inhibited thyroid cell line IHH-4, FTC-133, and 8505C cell proliferation and arrested cell cycle at G0/G1 stage and significantly decreased cyclin D1 and TSHR expressions (P < 0.05). Moreover, lncRNA PVT1 could be enriched by EZH2, and silencing PVT1 resulted in the decreased recruitment of EZH2. This study suggested that lncRNA PVT1 may contribute to tumorigenesis of thyroid cancer through recruiting EZH2 and regulating TSHR expression.

Keywords: Cell proliferation; Polycomb enhancer of zeste homolog 2 (EZH2); Thyroid cancer; Thyroid-stimulating hormone receptor (TSHR); lncRNA PVT1.

MeSH terms

  • Adult
  • Aged
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Enhancer of Zeste Homolog 2 Protein / physiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • RNA, Long Noncoding / analysis
  • RNA, Long Noncoding / physiology*
  • Receptors, Thyrotropin / physiology*
  • Thyroid Neoplasms / etiology
  • Thyroid Neoplasms / pathology*

Substances

  • PVT1 long-non-coding RNA, human
  • RNA, Long Noncoding
  • Receptors, Thyrotropin
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein