TET1 inhibits the migration and invasion of cervical cancer cells by regulating autophagy

ABSTRACT

Methylation modifications play pertinent roles in regulating gene expression and various biological processes. The silencing of the demethylase enzyme TET1 can affect the expressions of key oncogenes or tumour suppressor genes, thus contributing to tumour formation. Nonetheless, how TET1 affects the progression of cervical cancer is yet to be elucidated. In this study, we found that the expression of TET1 was significantly downregulated in cervical cancer tissues. Functionally, TET1 knockdown in cervical cancer cells can promote cell proliferation, migration, invasion, cervical xenograft tumour formation and EMT. On the contrary, its overexpression can reverse the aforementioned processes. Moreover, the autophagy level of cervical cancer cells can be enhanced after TET1 knockdown. Mechanistically, methylated DNA immunoprecipitation (MeDIP)-sequencing and MeDIP quantitative real-time PCR revealed that TET1 mediates the methylation of autophagy promoter regions. These findings suggest that TET1 affects the autophagy of cervical cancer cells by altering the methylation levels of NKRF or HIST1H2AK, but the specific mechanism needs to be investigated further.

KEYWORDS:

• Cervical cancer
• TET1
• autophagy
• EMT

Acknowledgments

We are grateful to each of the authors who contributed to this study and to the National Natural Science Foundation of China (NSFC, grant number, 81960473), Guangxi Zhuang Autonomous Natural Science Foundation (grant number, 2018JJB140322), the project of science and technology innovation for Postgraduates of Hubei Medical College (grant number, YC2019013, YC2019018), the Supplemental Fund Supporting the NSFC Project from the Guiyang Science and Technology Bureau (grant number Zhuke (2017) 30–36), and the Guizhou Provincial Education Research Project (grant number KY (2021)) for supporting this study.

Disclosure statement

The authors declare that they do not have financial or non-financial competing interests.

Author contributions

Concept presentation and experimental design: Yan Ding. Conduct of the experiment: Xiuying Chen, Jing Li, Ji Ren, Shan Wang, Yuxin Zhan. Data acquisition and analysis: Xiuying Chen, Yan Ding. Writing, reviewing and revising manuscripts: Ji Ren, Yan Ding. Study supervision: Yan Ding, Yujie Tan.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. All the sequencing data generated by this study have been deposited in NCBI’s Gene Expression Omnibus(GEO) under accession number GSE236396 and GSE236315. Data used to determine the effect of TET1 on autophagy signalling pathways in SiHa cells were derived from KEGG(https://www.genome.jp/kegg/).

Ethics approval and informed consent

This study was approved by the Ethics Committee of the Guizhou Medical University. Clinical tissue samples are handled in strict accordance with the ethical standards of the Declaration of Helsinki. All patients signed written informed consent. All procedures involving animal use were approved by the Animal Ethics Committee of the Guizhou Medical University and were in accordance with the National Policy on Use of Laboratory Animals. And all methods were performed in accordance with the relevant guidelines and regulations of the Basel Declaration. And the study is reported in accordance with ARRIVE guidelines.

Additional information

Funding

The present study was supported by the National Natural Science Foundation of China (NSFC, grant number, 81960473), Guangxi Zhuang Autonomous Natural Science Foundation (grant number, 2018JJB140322), the project of science and technology innovation for Postgraduates of Hubei Medical College (grant number, YC2019013, YC2019018), the Supplemental Fund Supporting the NSFC Project from the Guiyang Science and Technology Bureau (grant number Zhuke (2017) 30–36), and the Guizhou Provincial Education Research Project (grant number KY (2021)).