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ELK1 suppresses SYTL1 expression by recruiting HDAC2 in bladder cancer progression

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Abstract

ETS transcription factor (ELK1) stimulates the expression of genes at the onset of the cell cycle and participates in early developmental programming. Here, we investigated whether alterations of ELK1 lead to progression of bladder cancer (BCa), a main neoplasm of urinary tract, and clarified the function of ELK1 in BCa. Using the GEO database, we identified ELK1 as the most significantly overexpressed gene in BCa, which was substantiated in the acquired clinical samples and cells. Silencing of ELK1 inhibited the malignant phenotype of BCa cells. Further analysis revealed that ELK1 synergized with histone deacetylase 2 (HDAC2) to specifically bind to the synaptotagmin like 1 (SYTL1) promoter, thereby repressing SYTL1 transcription and protein expression. Depletion of SYTL1 reversed the repressive effects of ELK1 depletion on the malignant phenotype of BCa cells. Our in vitro findings were reproduced in vivo on a nude mouse tumorigenic model. Together, our results reveal that ELK1, through suppression of SYTL1 via HDAC2, supports the malignant phenotype of BCa cells.

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Availability of data and materials

The analyzed data sets generated during the study are available from the corresponding author on reasonable request.

Abbreviations

BCa:

Bladder cancer

ChIP:

Chromatin immunoprecipitation

ELK1:

ETS transcription factor

FBS:

Fetal bovine serum

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

HDAC2:

Histone deacetylase 2

RIPA:

Radioimmunoprecipitation assay

SYTL1:

Synaptotagmin like 1

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Funding

This work was supported by Natural Science Foundation of Hunan Province (No. 2021JJ30403).

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Authors and Affiliations

  1. Department of Urology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61, Jie Fang Xi Road, Changsha, 410005, Hunan, People’s Republic of China

    Jiansong Wang, Jianjun Luo, Xuecheng Wu & Zhuo Li

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  1. Jiansong Wang
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Contributions

JSW and JJL: Conceptualization, Manuscript preparation, Methodology, Experimental studies, Software; Statistical analysis; XCW and ZL: Visualization, Experimental studies, Statistical analysis; Data curation, Manuscript preparation, Reviewing and Editing, Validation; All authors read and approved the final manuscript.

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Correspondence to Zhuo Li.

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The authors declare no competing interests.

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Collection of samples and experiments with samples were approved by the Ethical Committee of Hunan Provincial People’s Hospital under Project License 20180122. Written informed consent for the present study was obtained from patients. All animal experimental procedures and animal care were in accordance with the guidelines provided by the NIH. The Animal Experiment Ethics Committee of Hunan Provincial People’s Hospital approved the experiments and projects related to experimental animals.

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Wang, J., Luo, J., Wu, X. et al. ELK1 suppresses SYTL1 expression by recruiting HDAC2 in bladder cancer progression. Human Cell 35, 1961–1975 (2022). https://doi.org/10.1007/s13577-022-00789-z

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