PRMT6 serves an oncogenic role in lung adenocarcinoma via regulating p18

Tang,Jie; Meng,Qinge; Shi,Ruirui; Xu,Youqi

doi:10.3892/mmr.2020.11402

PRMT6 serves an oncogenic role in lung adenocarcinoma via regulating p18

Authors:
- Jie Tang
- Qinge Meng
- Ruirui Shi
- Youqi Xu
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Affiliations: Department of Oncology, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210017, P.R. China
Published online on: August 3, 2020 https://doi.org/10.3892/mmr.2020.11402
Pages: 3161-3172
Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lung adenocarcinoma (LUAD), a major subtype of lung cancer, is the leading cause of cancer‑related mortality worldwide. Previous studies have determined the role of the protein arginine methyltransferases (PRMTs) in the physiology and pathology of LUAD. However, to the best of our knowledge, no empirical studies have been performed determining the association between protein arginine methyltransferase 6 (PRMT6) and LUAD. The present study aimed to determine the expression levels of PRMT6 in LUAD and its association with the clinicopathological characteristics. The effect of PRMT6 knockdown on cell growth was analyzed and chromatin immunoprecipitation (ChIP) assay was used to investigate the regulatory mechanisms of PRMT6 on downstream gene expression. In addition, a xenograft model was used to determine whether the PRMT6‑regulated expression levels of p18 in vitro could be validated in vivo. PRMT6 overexpression in LUAD is associated with high clinical stage, lymph node metastasis and poor clinical outcomes. Furthermore, the silencing of PRMT6 significantly reduced the enrichment of Histone H3 asymmetric demethylation at arginine 2 in the promoter region of the p18 gene, thereby activating the expression of the gene. This, in turn, induced G1/S phase cell cycle arrest, resulting in the inhibition of cell proliferation. The xenograft model also suggested that PRMT6 suppressed LUAD development by activating p18 expression in vivo. In conclusion, the findings of the present study suggested that PRMT6 may serve as an oncogene in the progression of LUAD through epigenetically suppressing p18 expression. Thus, PRMT6 may represent a novel potential therapeutic target for LUAD.

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