PITX1 inhibits the growth and proliferation of melanoma cells through regulation of SOX family genes

© 2021. The Author(s)..

Melanoma is one of the most aggressive types of cancer wherein resistance to treatment prevails. Therefore, it is important to discover novel molecular targets of melanoma progression as potential treatments. Here we show that paired-like homeodomain transcription factor 1 (PITX1) plays a crucial role in the inhibition of melanoma progression through regulation of SRY-box transcription factors (SOX) gene family mRNA transcription. Overexpression of PITX1 in melanoma cell lines resulted in a reduction in cell proliferation and an increase in apoptosis. Additionally, analysis of protein levels revealed an antagonistic cross-regulation between SOX9 and SOX10. Interestingly, PITX1 binds to the SOX9 promoter region as a positive regulatory transcription factor; PITX1 mRNA expression levels were positively correlated with SOX9 expression, and negatively correlated with SOX10 expression in melanoma tissues. Furthermore, transcription of the long noncoding RNA (lncRNA), survival-associated mitochondrial melanoma-specific oncogenic noncoding RNA (SAMMSON), was decreased in PITX1-overexpressing cells. Taken together, the findings in this study indicate that PITX1 may act as a negative regulatory factor in the development and progression of melanoma via direct targeting of the SOX signaling.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:11

Enthalten in:

Scientific reports - 11(2021), 1 vom: 15. Sept., Seite 18405

Sprache:

Englisch

Beteiligte Personen:

Ohira, Takahito [VerfasserIn]
Nakagawa, Suguru [VerfasserIn]
Takeshita, Jumpei [VerfasserIn]
Aburatani, Hiroyuki [VerfasserIn]
Kugoh, Hiroyuki [VerfasserIn]

Links:

Volltext

Themen:

Homeobox protein PITX1
Journal Article
Paired Box Transcription Factors
Research Support, Non-U.S. Gov't
SOX Transcription Factors

Anmerkungen:

Date Completed 16.12.2021

Date Revised 16.12.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41598-021-97791-6

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM330686100