Long Noncoding RNA AB074169 Inhibits Cell Proliferation via Modulation of KHSRP-Mediated CDKN1a Expression in Papillary Thyroid Carcinoma

• Published in: Cancer research (Chicago, Ill.) Ill.), 2018-08, Vol.78 (15), p.4163-4174
• Main Authors: Gou, Qiheng, Gao, Linbo, Nie, Xinwen, Pu, Wenchen, Zhu, Jingqiang, Wang, Yichao, Liu, Xuesha, Tan, Shuangyan, Zhou, Jian-Kang, Gong, Yanqiu, He, Juan, Wu, Ke, Xie, Yuxin, Zhao, Wanjun, Dai, Lunzhi, Liu, Lunxu, Xiang, Rong, Wei, Yu-Quan, Zhang, Lin, Peng, Yong
• Format: Article
• Language: English
• Subjects: Animals; Carcinogenesis - genetics; Cell Cycle Checkpoints - genetics; Cell growth; Cell Line, Tumor; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cyclin-dependent kinase 2; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Down-Regulation - genetics; Female; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Genes, Tumor Suppressor - physiology; GTP-binding protein; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Papillary thyroid carcinoma; Promoter Regions, Genetic - genetics; Ribonucleic acid; RNA; RNA Splicing - genetics; RNA, Long Noncoding - genetics; RNA-Binding Proteins - genetics; Splicing; Thyroid; Thyroid cancer; Thyroid Cancer, Papillary - genetics; Thyroid Neoplasms - genetics; Trans-Activators - genetics; Tumor suppressor genes; Tumorigenesis
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-17-3766

Long noncoding RNAs (lncRNA) are emerging as a novel class of regulators in gene expression associated with tumorigenesis. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is poorly understood. Here, we conducted global lncRNA profiling and identified lncRNA AB074169 (lncAB) as significantly downregulated in PTC. Decreased expression of lncAB in PTC was caused by CpG hypermethylation within its gene promoter. Functional studies showed that lncAB overexpression led to cell-cycle arrest and tumor growth inhibition and , whereas lncAB knockdown promoted cell proliferation. Mechanistic analyses revealed that lncAB bound KH-type splicing regulatory protein (KHSRP) and also decreased expression of KHSRP, thus increasing CDKN1a (p21) expression and decreasing CDK2 expression to repress cell proliferation. Taken together, these findings demonstrate that lncAB functions as a tumor suppressor during PTC tumorigenesis. These findings identify a tumor-suppressive long noncoding RNA in papillary thyroid carcinoma. http://cancerres.aacrjournals.org/content/canres/78/15/4163/F1.large.jpg .