Department of Otorhinolaryngology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
PeerJ. 2023 Mar 10;11:e14875. doi: 10.7717/peerj.14875. eCollection 2023.
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 TRA24 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.
RNA 结合代谢酶 LTA4H 是癌症化学预防和化疗的新靶点。最近的研究表明，LTA4H 在喉鳞状细胞癌（LSCC）中的表达增加促进了肿瘤的增殖、迁移和转移。然而，其机制尚不清楚。为了研究 LTA4H 在 LSCC 中的潜在作用，我们采用改良的 RNA 免疫沉淀和测序（iRIP-Seq）实验，获得了 HeLa 模型细胞（常用于分子机制研究的癌症模型细胞）中 LTA4H 结合 RNA 的表达谱。我们发现 LTA4H 广泛结合 mRNAs/pre-mRNAs 和 lncRNAs。在 LTA4H 结合峰中，与 TRA24 相互作用的 AAGG 基序的频率在两个重复中都很高。更值得注意的是，LTA4H 结合基因在有丝分裂细胞周期、DNA 修复、RNA 剪接相关途径和 RNA 代谢途径中显著富集，这意味着 LTA4H 具有与肿瘤相关的可变剪接调节功能。QRT-PCR 验证证实 LTA4H 特异性结合致癌基因的 mRNAs，包括 LTBP3、ROR2、EGFR、HSP90B1 和以 NEAT1 为代表的 lncRNAs。这些结果表明，LTA4H 可能作为 RNA 结合蛋白与与 LSCC 相关的基因结合，发挥癌症调节功能。我们的研究进一步揭示了 LTA4H 作为 LSCC 临床治疗靶点的分子机制。
