Int J Biol Sci 2022; 18(16):6145-6162. doi:10.7150/ijbs.75063 This issue Cite

Research Paper

ELK1-mediated YTHDF1 drives prostate cancer progression by facilitating the translation of Polo-like kinase 1 in an m6A dependent manner

Peizhang Li1#, Yuanping Shi2, Dajun Gao1, Huan Xu1, Yun Zou1✉, Zhong Wang1,3✉, Wenzhi Li1,4✉

1. Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
2. Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China.
3. Shanghai Key Lab of Tissue Engineering, Shanghai, China
4. Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
#Peizhang Li was First Author

Citation:
Li P, Shi Y, Gao D, Xu H, Zou Y, Wang Z, Li W. ELK1-mediated YTHDF1 drives prostate cancer progression by facilitating the translation of Polo-like kinase 1 in an m6A dependent manner. Int J Biol Sci 2022; 18(16):6145-6162. doi:10.7150/ijbs.75063. https://www.ijbs.com/v18p6145.htm
Other styles

File import instruction

Abstract

Graphic abstract

Background: N6-methyladenosine (m6A) is one of the most prevalent mRNA modifications in mammals, and it regulates the fate of modified RNA transcripts. In the current study, we aimed to elucidate the role of YTH m6A RNA-binding protein 1 (YTHDF1), a “reader” of m6A modification, in prostate cancer tumorigenesis.

Methods: We employed a multi-omics approach to detect the direct target of YTHDF1 upon manipulation of YTHDF1 expression in prostate cancer cells. Expression of YTHDF1 was also evaluated in human prostate tumors and either adjacent or paired normal tissues. Additionally, in vivo tumor growth and metastasis experimental assays were performed to evaluate the role of YTHDF1 in tumorigenesis. Finally, luciferase reporter assays and Chromatin immunoprecipitation (ChIP) were conducted to elucidate the transcriptional regulators of YTHDF1.

Results: We demonstrated that polo-like kinase 1 (PLK1) is a direct target of YTHDF1. YTHDF1 facilitated the translation efficiency of PLK1 in an m6A-dependent manner by identifying the m6A-modified PLK1 mRNA and subsequently promoted the hyperactivation of the PI3K/AKT signaling pathway. Moreover, our results indicated that YTHDF1 was upregulated in prostate cancer tissue and that high YTHDF1 expression was associated with adverse prognosis in patients with prostate cancer. Furthermore, upregulation of YTHDF1 promoted prostate cancer tumorigenesis and metastasis in vitro and in vivo. Additionally, dysregulation of ETS transcription factor ELK1 activated the transcription of YTHDF1 by directly binding to its promoter region.

Conclusions: Collectively, our findings suggest that the ELK1/YTHDF1/PLK1/PI3K/AKT axis is critical for prostate cancer progression and may serve as a potential therapeutic target for prostate cancer treatment.

Keywords: prostate cancer, N6-methyladenosine, YTHDF1, PLK1, ELK1


Citation styles

APA
Li, P., Shi, Y., Gao, D., Xu, H., Zou, Y., Wang, Z., Li, W. (2022). ELK1-mediated YTHDF1 drives prostate cancer progression by facilitating the translation of Polo-like kinase 1 in an m6A dependent manner. International Journal of Biological Sciences, 18(16), 6145-6162. https://doi.org/10.7150/ijbs.75063.

ACS
Li, P.; Shi, Y.; Gao, D.; Xu, H.; Zou, Y.; Wang, Z.; Li, W. ELK1-mediated YTHDF1 drives prostate cancer progression by facilitating the translation of Polo-like kinase 1 in an m6A dependent manner. Int. J. Biol. Sci. 2022, 18 (16), 6145-6162. DOI: 10.7150/ijbs.75063.

NLM
Li P, Shi Y, Gao D, Xu H, Zou Y, Wang Z, Li W. ELK1-mediated YTHDF1 drives prostate cancer progression by facilitating the translation of Polo-like kinase 1 in an m6A dependent manner. Int J Biol Sci 2022; 18(16):6145-6162. doi:10.7150/ijbs.75063. https://www.ijbs.com/v18p6145.htm

CSE
Li P, Shi Y, Gao D, Xu H, Zou Y, Wang Z, Li W. 2022. ELK1-mediated YTHDF1 drives prostate cancer progression by facilitating the translation of Polo-like kinase 1 in an m6A dependent manner. Int J Biol Sci. 18(16):6145-6162.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.