PMID- 36923505 OWN - NLM STAT- MEDLINE DCOM- 20230320 LR - 20230428 IS - 2167-8359 (Electronic) IS - 2167-8359 (Linking) VI - 11 DP - 2023 TI - LTA4H extensively associates with mRNAs and lncRNAs indicative of its novel regulatory targets. PG - e14875 LID - 10.7717/peerj.14875 [doi] LID - e14875 AB - The RNA-binding metabolic enzyme LTA4H is a novel target for cancer chemoprevention and chemotherapy. Recent research shows that the increased expression of LTA4H in laryngeal squamous cell carcinoma (LSCC) promotes tumor proliferation, migration, and metastasis. However, its mechanism remains unclear. 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. We found that LTA4H extensively binds with mRNAs/pre-mRNAs and lncRNAs. In the LTA4H binding peak, the frequency of the AAGG motif reported to interact with TRA2beta4 was high in both replicates. 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. QRT-PCR validation confirmed that LTA4H specifically binds to mRNAs of carcinogenesis-associated genes, including LTBP3, ROR2, EGFR, HSP90B1, and lncRNAs represented by NEAT1. These results suggest that LTA4H may combine with genes associated with LSCC as an RNA-binding protein to perform a cancer regulatory function. Our study further sheds light on the molecular mechanism of LTA4H as a clinical therapy target for LSCC. CI - (c)2023 Ren et al. FAU - Ren, Tianjiao AU - Ren T AD - Department of Otorhinolaryngology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Wang, Song AU - Wang S AD - Department of Otorhinolaryngology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Zhang, Bo AU - Zhang B AD - Department of Otorhinolaryngology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Zhou, Wei AU - Zhou W AD - Department of Otorhinolaryngology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Wang, Cansi AU - Wang C AD - Department of Otorhinolaryngology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Zhao, Xiaorui AU - Zhao X AD - Department of Otorhinolaryngology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Feng, Juan AU - Feng J AD - Department of Otorhinolaryngology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230310 PL - United States TA - PeerJ JT - PeerJ JID - 101603425 RN - 0 (RNA, Messenger) RN - 0 (RNA, Long Noncoding) SB - IM MH - Humans MH - RNA, Messenger/genetics MH - *RNA, Long Noncoding/genetics MH - *Carcinoma, Squamous Cell/genetics MH - Gene Expression Profiling MH - *Laryngeal Neoplasms/genetics MH - Squamous Cell Carcinoma of Head and Neck MH - *Head and Neck Neoplasms PMC - PMC10010175 OTO - NOTNLM OT - LTA4H OT - Laryngeal tumorigenesis OT - RNA-binding protein OT - iRIP-seq OT - lncRNA COIS- The authors declare there are no competing interests. EDAT- 2023/03/17 06:00 MHDA- 2023/03/21 06:00 PMCR- 2023/03/10 CRDT- 2023/03/16 02:24 PHST- 2022/08/31 00:00 [received] PHST- 2023/01/19 00:00 [accepted] PHST- 2023/03/16 02:24 [entrez] PHST- 2023/03/17 06:00 [pubmed] PHST- 2023/03/21 06:00 [medline] PHST- 2023/03/10 00:00 [pmc-release] AID - 14875 [pii] AID - 10.7717/peerj.14875 [doi] PST - epublish SO - PeerJ. 2023 Mar 10;11:e14875. doi: 10.7717/peerj.14875. eCollection 2023.