Department of Surgery, Yantai Yuhuangding Hospital, Affiliated with Medical College of Qingdao University, Yantai, China.
Cancer Res Treat. 2016 Apr;48(2):698-707. doi: 10.4143/crt.2015.118. Epub 2015 Aug 12.
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.
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.
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.
These findings indicate that BANCR may contribute to the tumorigenesis of PTC through regulation of cyclin D1 and TSHR.
长链非编码 RNA（lncRNA）在肿瘤发生中的重要性最近得到了证实。然而，lncRNA 在甲状腺癌发展中的作用在很大程度上仍然未知。
本研究采用定量逆转录聚合酶链反应，检测了三种 lncRNA 的表达，包括 BRAF 激活的长非编码 RNA（BANCR）、甲状腺乳头状癌易感候选基因 3（PTCSC3）和与丝裂原活化蛋白激酶途径和生长阻滞相关的非编码 RNA（NAMA）。
在甲状腺乳头状癌（PTC）与正常组织相比，BANCR 的表达显著上调，而 PTCSC3 和 NAMA 的表达显著下调。在 PTC 来源的细胞系（IHH-4）中敲低 BANCR 可显著抑制促甲状腺激素受体（TSHR）。BANCR 敲低还通过下调细胞周期蛋白 D1 导致细胞生长抑制和 G0/G1 期细胞周期停滞。此外，BANCR 被 polycomb 增强子同源物 2（EZH2）富集，沉默 BANCR 导致 EZH2 染色质募集减少，从而显著降低 TSHR 的表达。
这些发现表明，BANCR 可能通过调节细胞周期蛋白 D1 和 TSHR 促进 PTC 的肿瘤发生。
