Identification of targets of twist1 transcription factor in thyroid cancer cells

Gennaro Di Maro, Francesca Maria Orlandella, Tammaro Claudio Bencivenga, Paolo Salerno, Clara Ugolini, Fulvio Basolo, Roberta Maestro, Giuliana Salvatore

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Context: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human tumors. Twist1 is a basic helix-loop-helix transcription factor involved in cancer development and progression.We showed that Twist1 affects thyroid cancer cell survival and motility. Copyright

Objective: We aimed to identify Twist1 targets in thyroid cancer cells.

Design: Transcriptional targets of Twist1 were identified by gene expression profiling the TPCTwist1 cells in comparison with control cells. Functional studies were performed by silencing in TPC-Twist1 and in CAL62 cells the top 10 upregulated genes and by evaluating cell proliferation, survival, migration, and invasion. Chromatin immunoprecipitation was performed to verify direct binding of Twist1 to target genes. Quantitative RT-PCR was applied to study the expression level of Twist1 target genes in human thyroid carcinoma samples.

Results: According to the gene expression profile, the top functions enriched in TPC-Twist1 cells were cellular movement, cellular growth and proliferation, and cell death and survival. Silencing of the top 10 upregulated genes reduced viability of TPC-Twist1 and of CAL62 cells. Silencing of COL1A1, KRT7, and PDZK1 also induced cell death. Silencing of HS6ST2, THRB, ID4, RHOB, and PDZK1IP also impaired migration and invasion of TPC-Twist1 and of CAL62 cells. Chromatin immunoprecipitation showed that Twist1 directly binds the promoter of the top 10 upregulated genes. Quantitative RT-PCR showed that HS6ST2, COL1A1, F2RL1, LEPREL1, PDZK1, and PDZK1IP1 are overexpressed in thyroid carcinoma samples compared with normal thyroids.

Conclusions: We identified a set of genes that mediates Twist1 biological effects in thyroid cancer cells.

Original languageEnglish
Pages (from-to)E1617-E1626
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number9
DOIs
Publication statusPublished - Sep 1 2014

Fingerprint

Thyroid Neoplasms
Transcription Factors
Genes
Cells
Cell death
Gene expression
Cell Survival
Chromatin
Chromatin Immunoprecipitation
Basic Helix-Loop-Helix Transcription Factors
Cell Death
Cell Proliferation
Cell proliferation
Polymerase Chain Reaction
Tumors
Gene Expression Profiling
Transcriptome
Cell Movement
Neoplasms
Thyroid Gland

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Identification of targets of twist1 transcription factor in thyroid cancer cells. / Di Maro, Gennaro; Orlandella, Francesca Maria; Bencivenga, Tammaro Claudio; Salerno, Paolo; Ugolini, Clara; Basolo, Fulvio; Maestro, Roberta; Salvatore, Giuliana.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 99, No. 9, 01.09.2014, p. E1617-E1626.

Research output: Contribution to journalArticle

Di Maro, Gennaro ; Orlandella, Francesca Maria ; Bencivenga, Tammaro Claudio ; Salerno, Paolo ; Ugolini, Clara ; Basolo, Fulvio ; Maestro, Roberta ; Salvatore, Giuliana. / Identification of targets of twist1 transcription factor in thyroid cancer cells. In: Journal of Clinical Endocrinology and Metabolism. 2014 ; Vol. 99, No. 9. pp. E1617-E1626.
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AU - Di Maro, Gennaro

AU - Orlandella, Francesca Maria

AU - Bencivenga, Tammaro Claudio

AU - Salerno, Paolo

AU - Ugolini, Clara

AU - Basolo, Fulvio

AU - Maestro, Roberta

AU - Salvatore, Giuliana

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N2 - Context: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human tumors. Twist1 is a basic helix-loop-helix transcription factor involved in cancer development and progression.We showed that Twist1 affects thyroid cancer cell survival and motility. CopyrightObjective: We aimed to identify Twist1 targets in thyroid cancer cells.Design: Transcriptional targets of Twist1 were identified by gene expression profiling the TPCTwist1 cells in comparison with control cells. Functional studies were performed by silencing in TPC-Twist1 and in CAL62 cells the top 10 upregulated genes and by evaluating cell proliferation, survival, migration, and invasion. Chromatin immunoprecipitation was performed to verify direct binding of Twist1 to target genes. Quantitative RT-PCR was applied to study the expression level of Twist1 target genes in human thyroid carcinoma samples.Results: According to the gene expression profile, the top functions enriched in TPC-Twist1 cells were cellular movement, cellular growth and proliferation, and cell death and survival. Silencing of the top 10 upregulated genes reduced viability of TPC-Twist1 and of CAL62 cells. Silencing of COL1A1, KRT7, and PDZK1 also induced cell death. Silencing of HS6ST2, THRB, ID4, RHOB, and PDZK1IP also impaired migration and invasion of TPC-Twist1 and of CAL62 cells. Chromatin immunoprecipitation showed that Twist1 directly binds the promoter of the top 10 upregulated genes. Quantitative RT-PCR showed that HS6ST2, COL1A1, F2RL1, LEPREL1, PDZK1, and PDZK1IP1 are overexpressed in thyroid carcinoma samples compared with normal thyroids.Conclusions: We identified a set of genes that mediates Twist1 biological effects in thyroid cancer cells.

AB - Context: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human tumors. Twist1 is a basic helix-loop-helix transcription factor involved in cancer development and progression.We showed that Twist1 affects thyroid cancer cell survival and motility. CopyrightObjective: We aimed to identify Twist1 targets in thyroid cancer cells.Design: Transcriptional targets of Twist1 were identified by gene expression profiling the TPCTwist1 cells in comparison with control cells. Functional studies were performed by silencing in TPC-Twist1 and in CAL62 cells the top 10 upregulated genes and by evaluating cell proliferation, survival, migration, and invasion. Chromatin immunoprecipitation was performed to verify direct binding of Twist1 to target genes. Quantitative RT-PCR was applied to study the expression level of Twist1 target genes in human thyroid carcinoma samples.Results: According to the gene expression profile, the top functions enriched in TPC-Twist1 cells were cellular movement, cellular growth and proliferation, and cell death and survival. Silencing of the top 10 upregulated genes reduced viability of TPC-Twist1 and of CAL62 cells. Silencing of COL1A1, KRT7, and PDZK1 also induced cell death. Silencing of HS6ST2, THRB, ID4, RHOB, and PDZK1IP also impaired migration and invasion of TPC-Twist1 and of CAL62 cells. Chromatin immunoprecipitation showed that Twist1 directly binds the promoter of the top 10 upregulated genes. Quantitative RT-PCR showed that HS6ST2, COL1A1, F2RL1, LEPREL1, PDZK1, and PDZK1IP1 are overexpressed in thyroid carcinoma samples compared with normal thyroids.Conclusions: We identified a set of genes that mediates Twist1 biological effects in thyroid cancer cells.

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