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Introduction
Non-small cell lung carcinoma (NSCLC) accounts for ~85% of all lung cancer cases (1); lung adenocarcinoma (LUAD) is the main pathological type of NSCLC (2). The prognosis of lung cancer is related to the rate of recurrence, metastasis and chemotherapy resistance (3). The 5-year survival rate is 51.4% for patients with adenocarcinoma (4). The poor prognosis of lung cancer highlights the requirement for the development of novel biomarkers for the early diagnosis of the disease (5,6). Thus, there is an urgent need to improve the diagnosis and management of NSCLC.
Protein arginine methyltransferases (PRMTs) can be divided into three types: Asymmetrically, symmetrically and monomethylate protein arginines (type I/II/III, respectively) (7–9). Histone protein arginine methylation, catalyzed by PRMTs serves a crucial role in gene regulation (10). In addition, several non-histone substrates have also been discovered to be involved in gene transcription and protein translation (11). PRMTs were revealed to be widely expressed and activated in gastric and prostate cancer, as well as myeloid leukemia, where they were involved in cell growth, differentiation and apoptosis (12–15). In fact, the disruption of the modification catalyzed by PRMTs suppressed tumor development, indicating that PRMTs may be used as a potential therapeutic target for cancer (16). However, to the best of our knowledge, only a few studies have reported the dysregulation of PRMTs in lung cancer. For example, PRMT1 and PRMT4 were identified to be involved in the regulation of proliferation in lung cancer (17); and PRMT1 and PRMT5 were discovered to regulate apoptosis induced by doxorubicin or pemetrexed by affecting cellular FADD-like IL-1β-converting enzyme-inhibitory protein in NSCLC cells (18). In addition, enolase 1 methylation by PRMT5 was discovered to be critical for lung cancer cell invasion (19). Interestingly, to the best of our knowledge, no other PRMT members and their dysregulation were reported to be associated with lung cancer.
PRMT6, a type I arginine methyltransferase, has high affinity for the arginine-2 of Histone H3, specifically catalyzing Histone H3 asymmetric demethylation at arginine 2 (H3R2me2a) (10). PRMT6 was first identified to modify the glycine-and arginine-rich motifs (13), and subsequently reported to target histones and non-histones (20). However, the role of PRMT6 in human cancer remains controversial. The downregulation of PRMT6 expression levels has been reported in melanoma (21), while...