Research Paper Volume 13, Issue 12 pp 16287—16315
Immune infiltration-related N6-methyladenosine RNA methylation regulators influence the malignancy and prognosis of endometrial cancer
- 1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China
Received: December 2, 2020 Accepted: May 11, 2021 Published: June 16, 2021
https://doi.org/10.18632/aging.203157How to Cite
Copyright: © 2021 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
N6-methyladenosine (m6A) RNA methylation is associated with malignant tumor progression and is modulated by various m6A RNA methylation regulator proteins. However, its role in endometrial cancer is unclear. In this work, we analyzed sequence, copy number variation, and clinical data obtained from the TCGA database. Expression was validated using real-time quantitative polymerase chain reaction and immunohistochemistry. Changes in m6A RNA methylation regulators were closely related to the clinicopathological stage and prognosis of endometrial cancer. In particular, ZC3H13, YTHDC1, and METTL14 were identified as potential markers for endometrial cancer diagnosis and prognosis. The TIMER algorithm indicated that immune cell infiltration correlated with changes in ZC3H13, YTHDC1, and METTL14 expression. Meanwhile, ZC3H13 or YTHDC1 knockdown promoted the proliferation and invasion of endometrial cancer cells. Through gene enrichment analysis, we constructed a regulatory network in order to explore the potential molecular mechanism involving ZC3H13, YTHDC1, and METTL14. Virtual screening predicted interactions of potential therapeutic compounds with METTL14 and YTHDC1. These findings advance the understanding of RNA epigenetic modifications in endometrial cancer while identifying m6A regulators associated with immune infiltration, prognosis, and potential treatment strategies.
Abbreviations
EC: endometrial cancer; TCGA: The Cancer Genome Atlas; qRT-PCR: quantitative real-time PCR; KM: Kaplan-Meier; m6A: N6-methyladenosine; mRNA: messenger; tRNA: transfer RNA; rRNA: and ribosomal RNA; FTO: fluorine-doped tin oxide; PD-1: programmed cell death protein 1; PD-L1: programmed cell death protein-ligand 1; CNV: copy number variation; OS: overall survival; ZC3H13: Zinc finger CCCH domain-containing protein 13; XIST: X-inactive specific transcript; KEGG: Kyoto Encyclopedia of Genes and Genomes; CRCL: colorectal cancer.