Relationship of focally amplified long noncoding on chromosome 1 (FAL1) lncRNA with E2F transcription factors in thyroid cancer

Seonhyang Jeong, Jandee Lee, Daham Kim, Mi Youn Seol, Woo Kyung Lee, Jong Ju Jeong, Kee Hyun Nam, Sang Geun Jung, Dong Yeob Shin, Eunjig Lee, Woong Youn Chung, Young Suk Jo

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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 expressionwas significantly higher inPTCthan 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 andmay be associated with aggressive tumor behavior in PTC.

Original languageEnglish
JournalMedicine (United States)
Volume95
Issue number4
DOIs
Publication statusPublished - 2016 Jan 1

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Long Noncoding RNA
E2F Transcription Factors
Chromosomes, Human, Pair 1
Thyroid Neoplasms
Thyroid Gland
E2F2 Transcription Factor
Cell Cycle
E2F1 Transcription Factor
Genes
Neoplasms
Polymerase Chain Reaction
Messenger RNA
Papillary Thyroid cancer
Cyclin D1
Observational Studies
Multivariate Analysis
Cross-Sectional Studies
Gene Expression

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Jeong, Seonhyang ; Lee, Jandee ; Kim, Daham ; Seol, Mi Youn ; Lee, Woo Kyung ; Jeong, Jong Ju ; Nam, Kee Hyun ; Jung, Sang Geun ; Shin, Dong Yeob ; Lee, Eunjig ; Chung, Woong Youn ; Jo, Young Suk. / Relationship of focally amplified long noncoding on chromosome 1 (FAL1) lncRNA with E2F transcription factors in thyroid cancer. In: Medicine (United States). 2016 ; Vol. 95, No. 4.
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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 expressionwas significantly higher inPTCthan 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 andmay be associated with aggressive tumor behavior in PTC.",
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Relationship of focally amplified long noncoding on chromosome 1 (FAL1) lncRNA with E2F transcription factors in thyroid cancer. / Jeong, Seonhyang; Lee, Jandee; Kim, Daham; Seol, Mi Youn; Lee, Woo Kyung; Jeong, Jong Ju; Nam, Kee Hyun; Jung, Sang Geun; Shin, Dong Yeob; Lee, Eunjig; Chung, Woong Youn; Jo, Young Suk.

In: Medicine (United States), Vol. 95, No. 4, 01.01.2016.

Research output: Contribution to journalArticle

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T1 - Relationship of focally amplified long noncoding on chromosome 1 (FAL1) lncRNA with E2F transcription factors in thyroid cancer

AU - Jeong, Seonhyang

AU - Lee, Jandee

AU - Kim, Daham

AU - Seol, Mi Youn

AU - Lee, Woo Kyung

AU - Jeong, Jong Ju

AU - Nam, Kee Hyun

AU - Jung, Sang Geun

AU - Shin, Dong Yeob

AU - Lee, Eunjig

AU - Chung, Woong Youn

AU - Jo, Young Suk

PY - 2016/1/1

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N2 - 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 expressionwas significantly higher inPTCthan 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 andmay be associated with aggressive tumor behavior in PTC.

AB - 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 expressionwas significantly higher inPTCthan 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 andmay be associated with aggressive tumor behavior in PTC.

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