There is increasing evidence that LTA4H is overexpressed in many malignant cancers, which promotes cancer cell proliferation. However, more study is necessary to fully understand the specific molecular mechanism of LTA4H in laryngeal carcinoma. More importantly, studies have demonstrated that increased LTA4H expression in LSCC is associated with a poor prognosis, and knockdown of LTA4H successfully suppresses the growth, invasion and migration of laryngeal carcinoma cells ( Gao et al., 2019 Peyvandi et al., 2018). GO function was significantly enriched in RNA processing and respiratory electron transport chains, and LTA4H was one of the up-regulated proteins ( Peyvandi et al., 2018). A recent study screened 275 differential proteins associated with laryngeal cancer through PPI (protein-interaction) network analysis. The results showed that LTA4H was significantly up-regulated in LSCC tissues than in normal tissue. (2019) detected LTA4H expression in LSCC and normal tissue by qPCR. In recent years, researchers have found that many genes, miRNAs and lncRNAs are key factors of LSCC ( Zhang et al., 2016). Genes, miRNAs and lncRNAs all play key roles in tumor genesis and development. Hence, to better identify biomarkers and explore effective new therapeutic strategies, it is essential to reveal the LSCC’s carcinogenic mechanism. Studies have revealed lincRNA HOTAIR is highly expressed in LSCC and promotes methylation of PTEN ( Li et al., 2013). It has also been reported that the ANXA1 interaction with FPR2/ALX promote proliferation and metastasis of LSCC ( Gastardelo et al., 2014). Studies have shown that the prognosis of patients with LSCC with down-regulated HLA class I antigen was worse ( Ogino et al., 2006). An increasing amount of research demonstrates that the formation and development of LSCC is related to molecular mechanisms. Due to LSCC’s uncertain molecular mechanism, over 60% of patients were already at late stages when the disease was discovered ( Steuer et al., 2017). Due to the proneness to recurrence and metastasis, the five-year overall survival rate for LSCC has been approximately 50% in recent years ( Cavaliere et al., 2021). Research shows that nearly 180,000 new cases of throat cancer and nearly 100,000 throat cancer deaths were reported worldwide in one year ( Bray et al., 2018). 95 to 98% of laryngeal cancers are squamous cell carcinomas (LSCC) ( Zuo et al., 2016). Laryngeal cancer is not only the most common malignancy of the head and neck, but also the second most common respiratory system tumor after lung cancer. Our study further sheds light on the molecular mechanism of LTA4H as a clinical therapy target for LSCC. These results suggest that LTA4H may combine with genes associated with LSCC as an RNA-binding protein to perform a cancer regulatory function. QRT-PCR validation confirmed that LTA4H specifically binds to mRNAs of carcinogenesis-associated genes, including LTBP3, ROR2, EGFR, HSP90B1, and lncRNAs represented by NEAT1. More notably, LTA4H-binding genes were significantly enriched in the mitotic cell cycle, DNA repair, RNA splicing-related pathways, and RNA metabolism pathways, which means that LTA4H has tumor-related alternative splicing regulatory functions. In the LTA4H binding peak, the frequency of the AAGG motif reported to interact with TRA2 β4 was high in both replicates. We found that LTA4H extensively binds with mRNAs/pre-mRNAs and lncRNAs. To investigate the potential role of LTA4H in LSCC, we employed the improved RNA immunoprecipitation and sequencing (iRIP-Seq) experiment to get the expression profile of LTA4H binding RNA in HeLa model cells, a cancer model cell that is frequently used in molecular mechanism research. Recent research shows that the increased expression of LTA4H in laryngeal squamous cell carcinoma (LSCC) promotes tumor proliferation, migration, and metastasis. The RNA-binding metabolic enzyme LTA4H is a novel target for cancer chemoprevention and chemotherapy. LTA4H extensively associates with mRNAs and lncRNAs indicative of its novel regulatory targets. Cite this article Ren T, Wang S, Zhang B, Zhou W, Wang C, Zhao X, Feng J. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. Licence This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. Department of Otorhinolaryngology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China DOI 10.7717/peerj.14875 Published Accepted Received Academic Editor Vladimir Uversky Subject Areas Biochemistry, Cell Biology, Molecular Biology Keywords LTA4H, RNA-binding protein, lncRNA, iRIP-seq, Laryngeal tumorigenesis Copyright © 2023 Ren et al.
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