Cargando…

HOXB5 Overexpression Is Associated with Neuroendocrine Differentiation and Poor Prognosis in Prostate Cancer

Homeobox genes function as master regulatory transcription factors during embryogenesis. HOXB5 is known to play an important role in several cancers. However, the biological role of HOXB5 in prostate cancer (PCa) is not fully elucidated. This study aimed to analyze the expression and function of HOX...

Descripción completa

Detalles Bibliográficos
Autores principales: Sekino, Yohei, Pham, Quoc Thang, Kobatake, Kohei, Kitano, Hiroyuki, Ikeda, Kenichiro, Goto, Keisuke, Inoue, Shogo, Hayashi, Tetsutaro, Shiota, Masaki, Yasui, Wataru, Teishima, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389587/
https://www.ncbi.nlm.nih.gov/pubmed/34440097
http://dx.doi.org/10.3390/biomedicines9080893
_version_ 1783742893184253952
author Sekino, Yohei
Pham, Quoc Thang
Kobatake, Kohei
Kitano, Hiroyuki
Ikeda, Kenichiro
Goto, Keisuke
Inoue, Shogo
Hayashi, Tetsutaro
Shiota, Masaki
Yasui, Wataru
Teishima, Jun
author_facet Sekino, Yohei
Pham, Quoc Thang
Kobatake, Kohei
Kitano, Hiroyuki
Ikeda, Kenichiro
Goto, Keisuke
Inoue, Shogo
Hayashi, Tetsutaro
Shiota, Masaki
Yasui, Wataru
Teishima, Jun
author_sort Sekino, Yohei
collection PubMed
description Homeobox genes function as master regulatory transcription factors during embryogenesis. HOXB5 is known to play an important role in several cancers. However, the biological role of HOXB5 in prostate cancer (PCa) is not fully elucidated. This study aimed to analyze the expression and function of HOXB5 and involvement of HOXB5 in neuroendocrine differentiation in PCa. Immunohistochemistry showed that 56 (43.8%) of 128 cases of localized PCa were positive for HOXB5. HOXB5-positive cases were associated with poor prostate-specific antigen recurrence-free survival after prostatectomy. Among 74 cases of metastatic PCa, 43 (58.1%) were positive for HOXB5. HOXB5 expression was higher in metastatic PCa than that in localized PCa. HOXB5 knockdown suppressed cell growth and invasion, but HOXB5 overexpression increased cell growth and invasion in PCa cell lines. Furthermore, HOXB5 regulated RET expression. Gene set enrichment analysis revealed that Nelson androgen response gene set was enriched in low HOXB5 expression group. RB1 knockout increased HOXB5 expression. Of note, additional p53 knockdown further increased HOXB5 expression in RB1 knockout cells. In silico analysis showed that HOXB5 expression was increased in neuroendocrine PCa (NEPC). These results suggest that HOXB5 may be a promising prognostic marker after prostatectomy and is involved in progression to NEPC.
format Online
Article
Text
id pubmed-8389587
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83895872021-08-27 HOXB5 Overexpression Is Associated with Neuroendocrine Differentiation and Poor Prognosis in Prostate Cancer Sekino, Yohei Pham, Quoc Thang Kobatake, Kohei Kitano, Hiroyuki Ikeda, Kenichiro Goto, Keisuke Inoue, Shogo Hayashi, Tetsutaro Shiota, Masaki Yasui, Wataru Teishima, Jun Biomedicines Article Homeobox genes function as master regulatory transcription factors during embryogenesis. HOXB5 is known to play an important role in several cancers. However, the biological role of HOXB5 in prostate cancer (PCa) is not fully elucidated. This study aimed to analyze the expression and function of HOXB5 and involvement of HOXB5 in neuroendocrine differentiation in PCa. Immunohistochemistry showed that 56 (43.8%) of 128 cases of localized PCa were positive for HOXB5. HOXB5-positive cases were associated with poor prostate-specific antigen recurrence-free survival after prostatectomy. Among 74 cases of metastatic PCa, 43 (58.1%) were positive for HOXB5. HOXB5 expression was higher in metastatic PCa than that in localized PCa. HOXB5 knockdown suppressed cell growth and invasion, but HOXB5 overexpression increased cell growth and invasion in PCa cell lines. Furthermore, HOXB5 regulated RET expression. Gene set enrichment analysis revealed that Nelson androgen response gene set was enriched in low HOXB5 expression group. RB1 knockout increased HOXB5 expression. Of note, additional p53 knockdown further increased HOXB5 expression in RB1 knockout cells. In silico analysis showed that HOXB5 expression was increased in neuroendocrine PCa (NEPC). These results suggest that HOXB5 may be a promising prognostic marker after prostatectomy and is involved in progression to NEPC. MDPI 2021-07-26 /pmc/articles/PMC8389587/ /pubmed/34440097 http://dx.doi.org/10.3390/biomedicines9080893 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sekino, Yohei
Pham, Quoc Thang
Kobatake, Kohei
Kitano, Hiroyuki
Ikeda, Kenichiro
Goto, Keisuke
Inoue, Shogo
Hayashi, Tetsutaro
Shiota, Masaki
Yasui, Wataru
Teishima, Jun
HOXB5 Overexpression Is Associated with Neuroendocrine Differentiation and Poor Prognosis in Prostate Cancer
title HOXB5 Overexpression Is Associated with Neuroendocrine Differentiation and Poor Prognosis in Prostate Cancer
title_full HOXB5 Overexpression Is Associated with Neuroendocrine Differentiation and Poor Prognosis in Prostate Cancer
title_fullStr HOXB5 Overexpression Is Associated with Neuroendocrine Differentiation and Poor Prognosis in Prostate Cancer
title_full_unstemmed HOXB5 Overexpression Is Associated with Neuroendocrine Differentiation and Poor Prognosis in Prostate Cancer
title_short HOXB5 Overexpression Is Associated with Neuroendocrine Differentiation and Poor Prognosis in Prostate Cancer
title_sort hoxb5 overexpression is associated with neuroendocrine differentiation and poor prognosis in prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389587/
https://www.ncbi.nlm.nih.gov/pubmed/34440097
http://dx.doi.org/10.3390/biomedicines9080893
work_keys_str_mv AT sekinoyohei hoxb5overexpressionisassociatedwithneuroendocrinedifferentiationandpoorprognosisinprostatecancer
AT phamquocthang hoxb5overexpressionisassociatedwithneuroendocrinedifferentiationandpoorprognosisinprostatecancer
AT kobatakekohei hoxb5overexpressionisassociatedwithneuroendocrinedifferentiationandpoorprognosisinprostatecancer
AT kitanohiroyuki hoxb5overexpressionisassociatedwithneuroendocrinedifferentiationandpoorprognosisinprostatecancer
AT ikedakenichiro hoxb5overexpressionisassociatedwithneuroendocrinedifferentiationandpoorprognosisinprostatecancer
AT gotokeisuke hoxb5overexpressionisassociatedwithneuroendocrinedifferentiationandpoorprognosisinprostatecancer
AT inoueshogo hoxb5overexpressionisassociatedwithneuroendocrinedifferentiationandpoorprognosisinprostatecancer
AT hayashitetsutaro hoxb5overexpressionisassociatedwithneuroendocrinedifferentiationandpoorprognosisinprostatecancer
AT shiotamasaki hoxb5overexpressionisassociatedwithneuroendocrinedifferentiationandpoorprognosisinprostatecancer
AT yasuiwataru hoxb5overexpressionisassociatedwithneuroendocrinedifferentiationandpoorprognosisinprostatecancer
AT teishimajun hoxb5overexpressionisassociatedwithneuroendocrinedifferentiationandpoorprognosisinprostatecancer