Medical Center, Tsinghua University, Haidian, Beijing 100084, P.R. China.
Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, P.R. China.
Oncol Rep. 2017 Aug;38(2):1140-1148. doi: 10.3892/or.2017.5739. Epub 2017 Jun 22.
Pituitary null cell adenoma is a challenging clinical condition, and its pathogenesis remains to be elucidated. We performed this study to determine the roles of C5orf66-AS1, NORAD, and TINCR in the pathogenesis and invasion of pituitary null cell adenomas. Expression of the three long non-coding RNAs in pituitary null cell adenoma tissues of 11 patients and normal pituitary tissues from four donors was examined by performing quantitative reverse transcription-polymerase chain reaction. We found that C5orf66-AS1 expression was lower in pituitary null cell adenoma tissues than in normal pituitary tissues. Moreover, C5orf66-AS1 expression level was significantly lower in invasive pituitary null cell adenomas than in non-invasive ones. After transfection of C5orf66-AS1 into pituitary adenoma cells, assessment of cell viability and invasion suggested that overexpressed C5orf66-AS1 inhibited cell viability and cell invasion. In silico algorithms predicted several cis- and trans-acting target genes of C5orf66-AS1, including PITX1 and SCGB3A1. In addition, expression of some of the predicted target genes was determined using microarray data of another cohort with pituitary null cell adenomas. It showed that some of these target genes were differentially expressed between pituitary null cell adenoma tissues and normal pituitary tissues as well as between invasive and non-invasive tumors. Co-expression analysis in RNA sequencing data showed that PAQR7 was the most correlated gene of C5orf66-AS1 and that several predicted trans-acting target genes, including SCGB3A1, were highly correlated with C5orf66-AS1. NORAD and TINCR expression was not statistically significant in the complete cohort; however, a negative correlation was observed between NORAD expression and maximum tumor diameter in some subgroups. These results indicate that C5orf66-AS1 suppresses the development and invasion of pituitary null cell adenomas. However, our results do not provide enough statistical evidence to support the roles of NORAD and TINCR in the development and invasion of pituitary null cell adenomas.
垂体嫌色细胞瘤是一种具有挑战性的临床病症，其发病机制尚待阐明。我们进行这项研究旨在确定 C5orf66-AS1、NORAD 和 TINCR 在垂体嫌色细胞瘤的发病机制和侵袭中的作用。通过定量逆转录聚合酶链反应检测 11 例患者的垂体嫌色细胞瘤组织和 4 名供体的正常垂体组织中这三种长非编码 RNA 的表达。我们发现 C5orf66-AS1 在垂体嫌色细胞瘤组织中的表达低于正常垂体组织。此外，侵袭性垂体嫌色细胞瘤中 C5orf66-AS1 的表达水平明显低于非侵袭性肿瘤。转染 C5orf66-AS1 进入垂体瘤细胞后，评估细胞活力和侵袭性表明，过表达 C5orf66-AS1 抑制细胞活力和细胞侵袭。通过计算算法预测了 C5orf66-AS1 的几个顺式和反式作用靶基因，包括 PITX1 和 SCGB3A1。此外，使用另一组垂体嫌色细胞瘤的微阵列数据确定了一些预测靶基因的表达。结果表明，这些靶基因中的一些在垂体嫌色细胞瘤组织与正常垂体组织之间以及在侵袭性和非侵袭性肿瘤之间存在差异表达。RNA 测序数据的共表达分析表明，PAQR7 是 C5orf66-AS1 最相关的基因，几个预测的反式作用靶基因，包括 SCGB3A1，与 C5orf66-AS1 高度相关。NORAD 和 TINCR 在整个队列中的表达没有统计学意义；然而，在一些亚组中，NORAD 表达与最大肿瘤直径之间观察到负相关。这些结果表明 C5orf66-AS1 抑制了垂体嫌色细胞瘤的发生和侵袭。然而，我们的结果没有提供足够的统计证据支持 NORAD 和 TINCR 在垂体嫌色细胞瘤的发生和侵袭中的作用。
