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

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          Abstract

          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 in vitro and in vivo, 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.Significance: These findings identify a tumor-suppressive long noncoding RNA in papillary thyroid carcinoma.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/15/4163/F1.large.jpg Cancer Res; 78(15); 4163-74. ©2018 AACR.

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          Author and article information

          Journal
          Cancer Res.
          Cancer research
          American Association for Cancer Research (AACR)
          1538-7445
          0008-5472
          Aug 01 2018
          : 78
          : 15
          Affiliations
          [1 ] Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Collaborative Innovation Center of Biotherapy, Chengdu, China.
          [2 ] Department of Head and Neck Cancer, West China Hospital, Sichuan University, Chengdu, China.
          [3 ] Laboratory of Molecular and Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
          [4 ] Department of Immunology and Microbiology, Guangxi University of Traditional Chinese Medicine, Nanning, China.
          [5 ] Department of Thyroid Surgery, West China Hospital, Sichuan University, Chengdu, China.
          [6 ] Department of Clinical Medicine, School of Medicine, Nankai University, Tianjin, China.
          [7 ] Laboratory of Molecular and Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China. yongpeng@scu.edu.cn zhanglin@scu.edu.cn.
          [8 ] Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Collaborative Innovation Center of Biotherapy, Chengdu, China. yongpeng@scu.edu.cn zhanglin@scu.edu.cn.
          Article
          0008-5472.CAN-17-3766
          10.1158/0008-5472.CAN-17-3766
          29735546
          a33baa39-8d55-49cd-a3ec-1fdf4037fe84
          History

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