Aberrant overexpression of transcription factor Forkhead box D1 predicts poor prognosis and promotes cancer progression in HNSCC

Abstract Objectives Forkhead box D1, the core transcription factor member of FOX family, has gradually seen as a key cancerous regulatory. However, its expression and carcinogenicity in head and neck squamous cell carcinoma (HNSCC) have not been reported yet. This study was to investigate its expres...

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Autores principales: Jin Li, Tingyuan Yan, Xiang Wu, Xueping Ke, Xin Li, Yumin Zhu, Jianrong Yang, Zhongwu Li
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Publicado: BMC 2021
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spelling oai:doaj.org-article:e1624be5eac747168c71945882ed0f632021-11-14T12:30:38ZAberrant overexpression of transcription factor Forkhead box D1 predicts poor prognosis and promotes cancer progression in HNSCC10.1186/s12885-021-08868-41471-2407https://doaj.org/article/e1624be5eac747168c71945882ed0f632021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08868-4https://doaj.org/toc/1471-2407Abstract Objectives Forkhead box D1, the core transcription factor member of FOX family, has gradually seen as a key cancerous regulatory. However, its expression and carcinogenicity in head and neck squamous cell carcinoma (HNSCC) have not been reported yet. This study was to investigate its expression pattern, clinicopathological significance and biological roles in HNSCC. Methods HNSCC data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to indicate the detailed expression pattern and outcome association of FOXD1, while Western Blot assay to detect FOXD1 level in a panel of HNSCC cell lines as well as immunocytochemistry to explore FOXD1 protein abundance and sublocation. Series of siRNA-mediated FOXD1 knock-down experiments to assess the proliferation, migration, invasion and anti- apoptosis ability after FOXD1 down-regulation. Bioinformatic analysis to find out which biological function and cancer-related pathways of FOXD1 associated genes involved in. Results FOXD1 mRNA was significantly overexpressed in TCGA-HNSCC, GSE6631, GSE12452, GSE25099 and GSE30784. Besides, IHC results shown that nuclear location FOXD1 protein was significantly higher in primary HNSCC specimens from cohort involved in this study. Also, FOXD1 abundance was significantly correlated with cervical node metastasis and poor over-all/disease-free survival after combination analysis with patient pathological information. siRNA-mediated FOXD1 knock-down significantly inhibited cell proliferation, migration and invasion and induced apoptosis in HNSCC cells. Further analysis of GSEA, GO and KEGG showed that FOXD1 expression was significantly associated with oncological function and cancer-related pathways. Conclusions Taken together, our study implies that the potential oncogene, FOXD1, facilitates oncological behavior who can be identified as a brand-new HNSCC biomarker with diagnostic and prognostic significance.Jin LiTingyuan YanXiang WuXueping KeXin LiYumin ZhuJianrong YangZhongwu LiBMCarticleHead and neck squamous cell carcinoma (HNSCC)Forkhead box D1(FOXD1)ProliferationMigrationInvasionNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Head and neck squamous cell carcinoma (HNSCC)
Forkhead box D1(FOXD1)
Proliferation
Migration
Invasion
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle Head and neck squamous cell carcinoma (HNSCC)
Forkhead box D1(FOXD1)
Proliferation
Migration
Invasion
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Jin Li
Tingyuan Yan
Xiang Wu
Xueping Ke
Xin Li
Yumin Zhu
Jianrong Yang
Zhongwu Li
Aberrant overexpression of transcription factor Forkhead box D1 predicts poor prognosis and promotes cancer progression in HNSCC
description Abstract Objectives Forkhead box D1, the core transcription factor member of FOX family, has gradually seen as a key cancerous regulatory. However, its expression and carcinogenicity in head and neck squamous cell carcinoma (HNSCC) have not been reported yet. This study was to investigate its expression pattern, clinicopathological significance and biological roles in HNSCC. Methods HNSCC data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to indicate the detailed expression pattern and outcome association of FOXD1, while Western Blot assay to detect FOXD1 level in a panel of HNSCC cell lines as well as immunocytochemistry to explore FOXD1 protein abundance and sublocation. Series of siRNA-mediated FOXD1 knock-down experiments to assess the proliferation, migration, invasion and anti- apoptosis ability after FOXD1 down-regulation. Bioinformatic analysis to find out which biological function and cancer-related pathways of FOXD1 associated genes involved in. Results FOXD1 mRNA was significantly overexpressed in TCGA-HNSCC, GSE6631, GSE12452, GSE25099 and GSE30784. Besides, IHC results shown that nuclear location FOXD1 protein was significantly higher in primary HNSCC specimens from cohort involved in this study. Also, FOXD1 abundance was significantly correlated with cervical node metastasis and poor over-all/disease-free survival after combination analysis with patient pathological information. siRNA-mediated FOXD1 knock-down significantly inhibited cell proliferation, migration and invasion and induced apoptosis in HNSCC cells. Further analysis of GSEA, GO and KEGG showed that FOXD1 expression was significantly associated with oncological function and cancer-related pathways. Conclusions Taken together, our study implies that the potential oncogene, FOXD1, facilitates oncological behavior who can be identified as a brand-new HNSCC biomarker with diagnostic and prognostic significance.
format article
author Jin Li
Tingyuan Yan
Xiang Wu
Xueping Ke
Xin Li
Yumin Zhu
Jianrong Yang
Zhongwu Li
author_facet Jin Li
Tingyuan Yan
Xiang Wu
Xueping Ke
Xin Li
Yumin Zhu
Jianrong Yang
Zhongwu Li
author_sort Jin Li
title Aberrant overexpression of transcription factor Forkhead box D1 predicts poor prognosis and promotes cancer progression in HNSCC
title_short Aberrant overexpression of transcription factor Forkhead box D1 predicts poor prognosis and promotes cancer progression in HNSCC
title_full Aberrant overexpression of transcription factor Forkhead box D1 predicts poor prognosis and promotes cancer progression in HNSCC
title_fullStr Aberrant overexpression of transcription factor Forkhead box D1 predicts poor prognosis and promotes cancer progression in HNSCC
title_full_unstemmed Aberrant overexpression of transcription factor Forkhead box D1 predicts poor prognosis and promotes cancer progression in HNSCC
title_sort aberrant overexpression of transcription factor forkhead box d1 predicts poor prognosis and promotes cancer progression in hnscc
publisher BMC
publishDate 2021
url https://doaj.org/article/e1624be5eac747168c71945882ed0f63
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