UPF1-mediated mRNA decay promotes melanoma tumorigenesis through miR-101-3p-dependent destabilization of NANOS1.
5 affiliations
- 1Graduate School for Biomedical Science & Engineering, Hanyang University, Seoul, Korea.
- 2Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Korea.
- 3Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Korea.
- 4Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea.
- 5Research Institute for Convergence of Basic Sciences, Hanyang University, Seoul, Republic of Korea.
Abstract
Numerous studies have reported Up-frameshift protein 1 (UPF1) as a crucial posttranscriptional regulator in nonsense-mediated mRNA decay (NMD), attributing its role to tumorigenesis across various cancers. However, its recently unveiled function in UPF1-mediated mRNA decay (UMD), intricately coordinated with miRNA, remains unexplored in the context of tumorigenesis. Here, we demonstrate that UPF1 contributes to melanoma tumorigenesis by regulating NANOS1 expression in a miR-101-3p-dependent manner. Depletion of UPF1 across three melanoma cell lines significantly impaired cell growth, migration, and invasion by cell cycle arrest and disrupted tumor formation in vivo. Through comprehensive RNA-seq and biochemical analyses, we elucidate that attenuation of UPF1 leads to an increase in NANOS1 expression, consequently suppressing melanoma tumorigenesis. Mechanistically, UPF1 orchestrates the destabilization of NANOS1 via UPF1-mediated mRNA decay (UMD) facilitated by miR-101-3p. Intriguingly, UPF1 depletion and NANOS1 upregulation were associated with reduced ERK and ELK1 phosphorylation, suggesting that attenuation of MAPK/ERK/ELK1 signaling may contribute, at least in part, to the observed melanoma-suppressive phenotypes. Importantly, the biological relevance of UPF1 and NANOS1 in melanoma cell lines was further supported in drug-resistant melanoma cells and in xenograft mouse models. Collectively, these findings expand our understanding of UMD in melanoma and identify the UPF1/NANOS1 regulatory relationship as a potential therapeutic vulnerability in both parental and drug-resistant melanoma cells.
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BibTeX
@article{lee2026upf1mediated,
title = {{UPF1-mediated mRNA decay promotes melanoma tumorigenesis through miR-101-3p-dependent destabilization of NANOS1.}},
author = {Suman Lee and Jae-Won Yoon and Dayeon Woo and Hyunho Cha and Seungwon Jung and Je-Min Choi and Jungwook Hwang},
journal = {International journal of biological sciences},
year = {2026},
month = sep,
doi = {10.7150/ijbs.134804},
url = {https://europepmc.org/article/MED/42909927},
note = {CC BY},
}
RIS
TY - JOUR
TI - UPF1-mediated mRNA decay promotes melanoma tumorigenesis through miR-101-3p-dependent destabilization of NANOS1.
AU - Suman Lee
AU - Jae-Won Yoon
AU - Dayeon Woo
AU - Hyunho Cha
AU - Seungwon Jung
AU - Je-Min Choi
AU - Jungwook Hwang
PY - 2026
DA - 2026/09/24
JO - International journal of biological sciences
DO - 10.7150/ijbs.134804
UR - https://europepmc.org/article/MED/42909927
AB - Numerous studies have reported Up-frameshift protein 1 (UPF1) as a crucial posttranscriptional regulator in nonsense-mediated mRNA decay (NMD), attributing its role to tumorigenesis across various cancers. However, its recently unveiled function in UPF1-mediated mRNA decay (UMD), intricately coordinated with miRNA, remains unexplored in the context of tumorigenesis. Here, we demonstrate that UPF1 contributes to melanoma tumorigenesis by regulating NANOS1 expression in a miR-101-3p-dependent manner. Depletion of UPF1 across three melanoma cell lines significantly impaired cell growth, migration, and invasion by cell cycle arrest and disrupted tumor formation in vivo. Through comprehensive RNA-seq and biochemical analyses, we elucidate that attenuation of UPF1 leads to an increase in NANOS1 expression, consequently suppressing melanoma tumorigenesis. Mechanistically, UPF1 orchestrates the destabilization of NANOS1 via UPF1-mediated mRNA decay (UMD) facilitated by miR-101-3p. Intriguingly, UPF1 depletion and NANOS1 upregulation were associated with reduced ERK and ELK1 phosphorylation, suggesting that attenuation of MAPK/ERK/ELK1 signaling may contribute, at least in part, to the observed melanoma-suppressive phenotypes. Importantly, the biological relevance of UPF1 and NANOS1 in melanoma cell lines was further supported in drug-resistant melanoma cells and in xenograft mouse models. Collectively, these findings expand our understanding of UMD in melanoma and identify the UPF1/NANOS1 regulatory relationship as a potential therapeutic vulnerability in both parental and drug-resistant melanoma cells.
SN - 1449-2288
ER -