title: Relationship of Focally Amplified Long Noncoding on Chromosome 1 (FAL1) lncRNA with E2F Transcription Factors in Thyroid Cancer.
abstract: Recent functional genomic studies revealed that the oncogenic activity of focally amplified lncRNA on chromosome 1 (FAL1, ENSG00000228126) contributes to tumor growth by p21 repression in human cancers. However, the expression of FAL1 was not investigated in papillary thyroid cancer (PTC). We aimed to determine if FAL1 was up-regulated in PTC compared to paired contralateral normal thyroid tissues, and to investigate the potential targets of this lncRNA and its clinicopathological significance in PTC. We analyzed FAL1 and p21 expression levels in 100 PTC samples and matched normal thyroid tissue by qRT-PCR. Using lncRNA microarray data from the Gene Expression Omnibus (accession no. GSE61763), we explored potential targets of FAL1 by Gene Set Enrichment Analysis, followed by verification by qRT-PCR in our PTC samples. A cross-sectional observational study was conducted to investigate the relationship between patients' clinicopathological features and FAL1 expression. FAL1 expression was significantly higher in PTC than in paired normal thyroid tissues (paired t test, P < 0.001). p21 mRNA expression was also increased, not decreased, in PTC, and had no correlation with FAL1 expression (r = 0.0897, P = 0.4002). Gene Set Enrichment Analysis, using publicly available microarray data, indicated that a gene set related to the cell cycle, including E2F transcription factors 1 and 2, and cyclin D1, was coordinately enriched among samples with high FAL1 expression. A volcano plot showed that E2F1, E2F2, and VEGFA mRNAs were increased in the high FAL1 samples. In clinicopathological analyses, multifocality was more frequently observed in PTC patients with high FAL1 (P = 0.018). Multivariate analysis showed that high FAL1 expression increased the risk of multifocality (after adjustment for clinical variables, OR = 4.019, CI = 1.041-11.020, P = 0.043). FAL1 may have a role in cell-cycle progression and may be associated with aggressive tumor behavior in PTC.
authors.affiliation: From the Departments of Internal Medicine (SJ, DK, WKL, DYS, EJL, YSJ) and Surgery (JL, M-YS, JJJ, K-HN, WYC), Open NBI Convergence Technology Research Laboratory, Severance Hospital, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea; and Department of Gynecological Oncology, Bundang CHA Medical Center, CHA University, Gyeonggi-do, South Korea (SGJ).
authors.forename: Seonhyang
authors.initials: S
authors.lastname: Jeong
authors.forename: Jandee
authors.initials: J
authors.lastname: Lee
authors.forename: Daham
authors.initials: D
authors.lastname: Kim
authors.forename: Mi-Youn
authors.initials: MY
authors.lastname: Seol
authors.forename: Woo Kyung
authors.initials: WK
authors.lastname: Lee
authors.forename: Jong Ju
authors.initials: JJ
authors.lastname: Jeong
authors.forename: Kee-Hyun
authors.initials: KH
authors.lastname: Nam
authors.forename: Sang Geun
authors.initials: SG
authors.lastname: Jung
authors.forename: Dong Yeob
authors.initials: DY
authors.lastname: Shin
authors.forename: Eun Jig
authors.initials: EJ
authors.lastname: Lee
authors.forename: Woong Youn
authors.initials: WY
authors.lastname: Chung
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Jo
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D003430:Cross-Sectional Studies; D019938:Cyclin D1 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000235:genetics*; D050703:E2F2 Transcription Factor / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C000608017:focally amplified long noncoding RNA on chromosome 1, human; D019938:Cyclin D1
references.citation: Nat Rev Drug Discov. 2013 Jun;12(6):433-46
references.pmid: 23722346
references.citation: J Clin Endocrinol Metab. 2015 Jan;100(1):E164-72
references.pmid: 25303483
references.citation: Cancer Cell. 2014 Sep 8;26(3):344-357
references.pmid: 25203321
references.citation: J Clin Endocrinol Metab. 2015 Apr;100(4):E632-7
references.pmid: 25584719
references.citation: Oncol Lett. 2014 Nov;8(5):1947-1952
references.pmid: 25289082
references.citation: Cancer Discov. 2013 May;3(5):520-33
references.pmid: 23365119
references.citation: Int J Cancer. 2007 Aug 15;121(4):767-75
references.pmid: 17415708
references.citation: N Engl J Med. 2015 Feb 12;372(7):621-30
references.pmid: 25671254
references.citation: JAMA. 2013 Apr 10;309(14):1493-501
references.pmid: 23571588
references.citation: Int J Cancer. 1995 Nov 27;63(5):611-5
references.pmid: 7591274
references.citation: Cancer Res. 1995 Jul 1;55(13):2910-9
references.pmid: 7796420
references.citation: Nat Rev Endocrinol. 2015 Mar;11(3):151-60
references.pmid: 25560704
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2803-8
references.pmid: 17296934
references.citation: Nat Rev Genet. 2014 Jan;15(1):7-21
references.pmid: 24296535
references.citation: Genome Biol. 2015 Jan 30;16:24
references.pmid: 25723451
references.citation: J Clin Endocrinol Metab. 2006 Sep;91(9):3667-70
references.pmid: 16772349
references.citation: JAMA. 2006 May 10;295(18):2164-7
references.pmid: 16684987
references.citation: J Clin Endocrinol Metab. 1990 Aug;71(2):414-24
references.pmid: 2380337
references.citation: Nature. 2010 Dec 16;468(7326):973-7
references.pmid: 21107323
references.citation: N Engl J Med. 2014 Nov 6;371(19):1765-7
references.pmid: 25372084
references.citation: Nat Biotechnol. 2012 Mar 25;30(5):453-9
references.pmid: 22446693
references.citation: Nucleic Acids Res. 2009 Jul;37(Web Server issue):W277-80
references.pmid: 19435882
references.citation: Nat Rev Genet. 2011 Nov 18;12(12):861-74
references.pmid: 22094949
references.citation: World J Surg. 2013 Feb;37(2):376-84
references.pmid: 23135422
references.citation: Gene. 1996 Sep 16;173(2):163-9
references.pmid: 8964493
references.citation: Nat Rev Genet. 2014 Jun;15(6):423-37
references.pmid: 24776770
references.citation: J Clin Endocrinol Metab. 2015 Apr;100(4):1619-29
references.pmid: 25632969
references.citation: Clin Cancer Res. 1996 Sep;2(9):1591-9
references.pmid: 9816338
references.citation: Thyroid. 2009 Nov;19(11):1167-214
references.pmid: 19860577
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
references.pmid: 16199517
references.citation: Medicine (Baltimore). 2015 Jan;94(2):e380
references.pmid: 25590838
references.citation: Ann Surg. 2007 Sep;246(3):375-81; discussion 381-4
references.pmid: 17717441
references.citation: Mol Cell Biol. 1999 Mar;19(3):2400-7
references.pmid: 10022926
references.citation: Lancet. 2014 Jul 26;384(9940):319-28
references.pmid: 24768112
references.citation: Nature. 2010 Sep 30;467(7315):596-9
references.pmid: 20823850
references.citation: J Clin Endocrinol Metab. 2012 Apr;97(4):1250-7
references.pmid: 22319042
references.citation: Medicine (Baltimore). 2015 Feb;94(6):e548
references.pmid: 25674762
references.citation: Mol Cancer Res. 2003 Nov;1(13):948-58
references.pmid: 14638867
references.citation: Endocr Relat Cancer. 2015 Apr;22(2):159-68
references.pmid: 25593071
references.citation: Nature. 2009 Mar 12;458(7235):223-7
references.pmid: 19182780
references.citation: J Clin Oncol. 2015 Jan 1;33(1):42-50
references.pmid: 25332244
references.citation: J Clin Oncol. 2014 Sep 1;32(25):2718-26
references.pmid: 25024077
references.citation: Proc Natl Acad Sci U S A. 2012 May 29;109(22):8646-51
references.pmid: 22586128
references.citation: Nucleic Acids Res. 2012 Nov 1;40(20):10018-31
references.pmid: 22923516
references.citation: Nat Rev Genet. 2015 Jan;16(1):7-17
references.pmid: 25385129
references.citation: World J Surg. 2002 Aug;26(8):879-85
references.pmid: 12016468
references.citation: Cancer Res. 2005 May 15;65(10):3980-5
references.pmid: 15899785
references.citation: Nat Rev Mol Cell Biol. 2002 Jan;3(1):11-20
references.pmid: 11823794
references.citation: Gene. 2015 Sep 10;569(1):109-17
references.pmid: 26003293
references.citation: Cell Mol Immunol. 2014 Jan;11(1):79-83
references.pmid: 24240124
references.citation: J Clin Endocrinol Metab. 2014 Feb;99(2):E276-85
references.pmid: 24248188