Ultraviolet B Exposure Does Not Influence the Expression of YAP mRNA in Human Epidermal Keratinocytes—Preliminary Study

<b>Background:</b> The causal relationship between exposure to ultraviolet radiation and the development of skin cancers requires constant research for possible orchestrating mechanisms. In recent years, the Hippo pathway, along with its effector protein YAP, became implicated in cutaneo...

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Main Authors: Igor Aleksander Bednarski, Izabela Dróżdż, Magdalena Ciążyńska, Karolina Wódz, Joanna Narbutt, Aleksandra Lesiak
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/3/596
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author Igor Aleksander Bednarski
Izabela Dróżdż
Magdalena Ciążyńska
Karolina Wódz
Joanna Narbutt
Aleksandra Lesiak
author_facet Igor Aleksander Bednarski
Izabela Dróżdż
Magdalena Ciążyńska
Karolina Wódz
Joanna Narbutt
Aleksandra Lesiak
author_sort Igor Aleksander Bednarski
collection DOAJ
description <b>Background:</b> The causal relationship between exposure to ultraviolet radiation and the development of skin cancers requires constant research for possible orchestrating mechanisms. In recent years, the Hippo pathway, along with its effector protein YAP, became implicated in cutaneous carcinogenesis; however, Hippo pathway regulation by ultraviolet radiation has not been described thoroughly. In order to address this issue, we focused on how different doses of ultraviolet B affect Hippo signaling pathway components and its upstream regulators, JNK1/2 and ABL1, in human keratinocytes. Additionally, we decided to determine how silencing of YAP influences Hippo pathway component expression. <b>Methods:</b> Primary epidermal keratinocytes were irradiated using UVB lamps with increasing doses of ultraviolet B radiation (including 311 nm UVB). Real-time PCR was used to determine the mRNA levels of each investigated gene. The experiment was then performed after YAP silencing using siRNA transfection. Additionally, we determined the mRNA expression of Hippo pathway components in an A431 cSCC cell line. <b>Results:</b> We observed that YAP mRNA expression in the A431 cell line was insignificant in comparison to control, while in the case of LATS1/2, a significant increase was noted. UVB irradiation did not change the levels of YAP mRNA expression in human epidermal keratinocytes. LATS1, LATS2, ABL1 and MAP4K4 mRNA expression was significantly upregulated after UVB irradiation in non-YAP-silenced keratinocytes in a dose-dependent manner, while after YAP silencing, only LATS2 and ABL1 showed significant mRNA upregulation. The 311 nm UVB irradiation resulted in significant, dose-dependent mRNA upregulation in non-YAP-silenced keratinocytes for LATS1, ABL1 and MAP4K4. After YAP silencing, a significant change in mRNA expression was present only in the case of ABL1. <b>Conclusions:</b> YAP mRNA expression does not significantly increase after exposure to UVB; however, it upregulates the expression of its proven (LATS1/2, JNK1/2) regulators, suggesting that in real-life settings, UV-induced dysregulation of the Hippo pathway may not be limited to YAP.
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issn 2227-9059
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spelling doaj-art-10990dfd8edb4a52a524a9ad625b5c062025-08-20T02:42:35ZengMDPI AGBiomedicines2227-90592025-03-0113359610.3390/biomedicines13030596Ultraviolet B Exposure Does Not Influence the Expression of YAP mRNA in Human Epidermal Keratinocytes—Preliminary StudyIgor Aleksander Bednarski0Izabela Dróżdż1Magdalena Ciążyńska2Karolina Wódz3Joanna Narbutt4Aleksandra Lesiak5Dermatology, Pediatric Dermatology and Dermatological Oncology Clinic, Medical University of Łódź, 91-347 Łódź, PolandDepartment of Clinical Genetics, Medical University of Łódź, 92-213 Łódź, PolandDepartment of Proliferative Diseases, Nicolaus Copernicus Multidisciplinary Centre for Oncology and Traumatology, Medical University of Łódź, 93-513 Łódź, PolandLaboratory of Molecular Biology, Vet-Lab Brudzew, 62-720 Brudzew, PolandDermatology, Pediatric Dermatology and Dermatological Oncology Clinic, Medical University of Łódź, 91-347 Łódź, PolandDermatology, Pediatric Dermatology and Dermatological Oncology Clinic, Medical University of Łódź, 91-347 Łódź, Poland<b>Background:</b> The causal relationship between exposure to ultraviolet radiation and the development of skin cancers requires constant research for possible orchestrating mechanisms. In recent years, the Hippo pathway, along with its effector protein YAP, became implicated in cutaneous carcinogenesis; however, Hippo pathway regulation by ultraviolet radiation has not been described thoroughly. In order to address this issue, we focused on how different doses of ultraviolet B affect Hippo signaling pathway components and its upstream regulators, JNK1/2 and ABL1, in human keratinocytes. Additionally, we decided to determine how silencing of YAP influences Hippo pathway component expression. <b>Methods:</b> Primary epidermal keratinocytes were irradiated using UVB lamps with increasing doses of ultraviolet B radiation (including 311 nm UVB). Real-time PCR was used to determine the mRNA levels of each investigated gene. The experiment was then performed after YAP silencing using siRNA transfection. Additionally, we determined the mRNA expression of Hippo pathway components in an A431 cSCC cell line. <b>Results:</b> We observed that YAP mRNA expression in the A431 cell line was insignificant in comparison to control, while in the case of LATS1/2, a significant increase was noted. UVB irradiation did not change the levels of YAP mRNA expression in human epidermal keratinocytes. LATS1, LATS2, ABL1 and MAP4K4 mRNA expression was significantly upregulated after UVB irradiation in non-YAP-silenced keratinocytes in a dose-dependent manner, while after YAP silencing, only LATS2 and ABL1 showed significant mRNA upregulation. The 311 nm UVB irradiation resulted in significant, dose-dependent mRNA upregulation in non-YAP-silenced keratinocytes for LATS1, ABL1 and MAP4K4. After YAP silencing, a significant change in mRNA expression was present only in the case of ABL1. <b>Conclusions:</b> YAP mRNA expression does not significantly increase after exposure to UVB; however, it upregulates the expression of its proven (LATS1/2, JNK1/2) regulators, suggesting that in real-life settings, UV-induced dysregulation of the Hippo pathway may not be limited to YAP.https://www.mdpi.com/2227-9059/13/3/596ultraviolet BHippo pathwayYAPskin carcinogenesis
spellingShingle Igor Aleksander Bednarski
Izabela Dróżdż
Magdalena Ciążyńska
Karolina Wódz
Joanna Narbutt
Aleksandra Lesiak
Ultraviolet B Exposure Does Not Influence the Expression of YAP mRNA in Human Epidermal Keratinocytes—Preliminary Study
Biomedicines
ultraviolet B
Hippo pathway
YAP
skin carcinogenesis
title Ultraviolet B Exposure Does Not Influence the Expression of YAP mRNA in Human Epidermal Keratinocytes—Preliminary Study
title_full Ultraviolet B Exposure Does Not Influence the Expression of YAP mRNA in Human Epidermal Keratinocytes—Preliminary Study
title_fullStr Ultraviolet B Exposure Does Not Influence the Expression of YAP mRNA in Human Epidermal Keratinocytes—Preliminary Study
title_full_unstemmed Ultraviolet B Exposure Does Not Influence the Expression of YAP mRNA in Human Epidermal Keratinocytes—Preliminary Study
title_short Ultraviolet B Exposure Does Not Influence the Expression of YAP mRNA in Human Epidermal Keratinocytes—Preliminary Study
title_sort ultraviolet b exposure does not influence the expression of yap mrna in human epidermal keratinocytes preliminary study
topic ultraviolet B
Hippo pathway
YAP
skin carcinogenesis
url https://www.mdpi.com/2227-9059/13/3/596
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AT magdalenaciazynska ultravioletbexposuredoesnotinfluencetheexpressionofyapmrnainhumanepidermalkeratinocytespreliminarystudy
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