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01-11-2024 | Cervical Cancer | Original Paper

PARP1 acetylation at K119 is essential in regulating the progression and proliferation of cervical cancer cells

Authors: Li-Li Yang, Xue-Ke Zhang, Ying Cao, Li-Ya Shi, Shi-Ya Xie, Yan-Jie Yang, Shao-Jun Wu, Hong-Zhan Sun, Xue-Jun Tang, Dong-Lan Yuan, Dong Zhang, Xiao-Feng Xu, Qian Li, Xiao-Yan Ying

Published in: Medical Oncology | Issue 11/2024

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Abstract

Cervical cancer, CC, is one of the malignant cancers in women worldwide. Many studies about the genesis and progression of CC have been done at genomic, transcriptional, translational, and epigenetic levels. However, much less is done at post-translational modification (PTM) level. We first used pan-PTM antibodies to compare the pan PTM levels between clinical normal cervical tissues and CC tissues; we then sent the selected samples for label-free identification of acetylation sites. Next, we employed WT or K119A mutant PARP1-EGFP-STREPII plasmid transfection in Hela cells and examined various indexes including colony formation, wound healing, ROS generation, early apoptosis, and immunofluorescence and quantification of proliferation markers (Ki67, PCNA, and p-P53). Last, we examined the levels of multiple important kinases regulating cervical cancer progression. We found that pan-acetylation was the most downregulated in clinical CC samples, whereas the acetylation of PARP1, Poly(ADP-ribose) polymerase-1, was upregulated at K119. Next, we showed that PARP1-WT overexpression significantly suppressed the proliferation and progression in CC cell line Hela, while K119A overexpression didn’t show any impact. Finally, PARP1-WT overexpression significantly decreased p-ERK1/2 while didn’t affect the phosphorylation levels of other important kinases such as AKT, MTOR, and RPS6. This study discovered a new type of PTM of PARP1 in CC, and showed that PARP1 acetylation at K119 is essential in regulating the proliferation and progression of CC through ERK1/2. Further studies are required to investigate how PARP1 acetylation impact its function.
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Metadata
Title
PARP1 acetylation at K119 is essential in regulating the progression and proliferation of cervical cancer cells
Authors
Li-Li Yang
Xue-Ke Zhang
Ying Cao
Li-Ya Shi
Shi-Ya Xie
Yan-Jie Yang
Shao-Jun Wu
Hong-Zhan Sun
Xue-Jun Tang
Dong-Lan Yuan
Dong Zhang
Xiao-Feng Xu
Qian Li
Xiao-Yan Ying
Publication date
01-11-2024
Publisher
Springer US
Published in
Medical Oncology / Issue 11/2024
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-024-02315-7

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