Chen Cunrong, Zhou Lili, Wang Hui, Chen Junnian, Li Wen, Liu Wei, Shen Mingjie, Liu Hongzhou, Fu Xiaomin
Department of ICU, Fujian Medical University Union HospitalFuzhou, Fujian, China.
Department of Gynecology and Obstetrics of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai, China.
Am J Cancer Res. 2018 Jan 1;8(1):192-206. eCollection 2018.
Several somatic copy number variations (CNVs) have been identified in papillary thyroid cancer (PTC). However, the functional roles of CNVs and the genes responsible for the roles of CNVs are largely unknown. In this study, we identified a novel long noncoding RNA (lncRNA) CNALPTC1 (copy number amplified long noncoding RNA in papillary thyroid cancer 1). The genomic copy number of is amplified and CNALPTC1 expression level is up-regulated in PTC. Increased expression of CNALPTC1 is associated with aggressive clinicopathological characteristics. Gain-of-function and loss-of-function assays revealed that CNALPTC1 promotes proliferation and migration of PTC cells, and inhibits apoptosis of PTC cells. Mechanistically, we found that CNALPTC1 physically associates to miR-30 family and down-regulates miR-30 expression. Furthermore, CNALPTC1 up-regulates the expression of miR-30 targets, such as BCL9, SNAI1, and VIM. The mutation of miR-30 binding site on CNALPTC1 or overexpression of miR-30 abrogates the oncogenic roles of CNALPTC1 in PTC. Collectively, our results suggested that the copy number amplified lncRNA CNALPTC1 promotes PTC progression via sponging miR-30 family. Our data also implied that CNALPTC1 may be a novel therapeutic target for PTC.
在甲状腺乳头状癌（PTC）中已鉴定出几种体细胞拷贝数变异（CNV）。然而，CNV的功能作用以及负责CNV作用的基因在很大程度上尚不清楚。在本研究中，我们鉴定了一种新型长链非编码RNA（lncRNA）CNALPTC1（甲状腺乳头状癌1中拷贝数扩增的长链非编码RNA）。其基因组拷贝数在PTC中扩增，且CNALPTC1表达水平上调。CNALPTC1表达增加与侵袭性临床病理特征相关。功能获得和功能丧失试验表明，CNALPTC1促进PTC细胞的增殖和迁移，并抑制PTC细胞的凋亡。机制上，我们发现CNALPTC1与miR-30家族物理结合并下调miR-30表达。此外，CNALPTC1上调miR-30靶标的表达，如BCL9、SNAI1和VIM。CNALPTC1上miR-30结合位点的突变或miR-30的过表达消除了CNALPTC1在PTC中的致癌作用。总体而言，我们的结果表明，拷贝数扩增的lncRNA CNALPTC1通过海绵化miR-30家族促进PTC进展。我们的数据还暗示CNALPTC1可能是PTC的一个新的治疗靶点。
