DNA methylation, an epigenetic regulatory mechanism dictating gene transcription, plays a critical role in the occurrence and development of cancer. However, the molecular underpinnings of LINC00987 methylation in the regulation of lung adenocarcinoma (LUAD) remain elusive. This study investigated LINC00987 expression in LUAD patients through analysis of The Cancer Genome Atlas data sets. Quantitative real‐time polymerase chain reaction (RT‐qPCR) and fluorescence in situ hybridization assays were used to assess LINC00987 expression in LUAD. The bisulfite genomic sequence PCR (BSP) assay was used to determine the methylation levels of the LINC00987 promoter. The interaction between LINC00987 and SND1 was elucidated via immunoprecipitation and RNA pull‐down assays. The functional significance of LINC00987 and SND1 in Calu‐3 and NCI‐H1688 cells was evaluated in vitro through CCK‐8, EdU, Transwell, flow cytometry, and vasculogenic mimicry (VM) tube formation assays. LINC00987 expression decreased in LUAD concomitant with hypermethylation of the promoter region, while hypomethylation of the LINC00987 promoter in LUAD tissues correlated with tumor progression. Treatment with 5‐Aza‐CdR augmented LINC00987 expression and inhibited tumor growth. Mechanistically, LINC00987 overexpression impeded LUAD progression and VM through direct binding with SND1, thereby facilitating its phosphorylation and subsequent degradation. Additionally, overexpression of SND1 counteracted the adverse effects of LINC00987 downregulation on cell proliferation, apoptosis, cell migration, invasion, and VM in LUAD in vitro. In conclusion, this pioneering study focuses on the expression and function of LINC00987 and reveals that hypermethylation of the LINC00987 gene may contribute to LUAD progression. LINC00987 has emerged as a potential tumor suppressor gene in tumorigenesis through its binding with SND1 to facilitate its phosphorylation and subsequent degradation.

中文翻译：

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低甲基化相关的 LINC00987 下调通过抑制磷酸化介导的 SND1 降解诱导肺腺癌进展

DNA甲基化是一种决定基因转录的表观遗传调控机制，在癌症的发生和发展中起着至关重要的作用。然而，LINC00987 甲基化在肺腺癌 (LUAD) 调节中的分子基础仍然难以捉摸。本研究通过分析癌症基因组图谱数据集调查了 LUAD 患者中的 LINC00987 表达。使用定量实时聚合酶链反应 (RT-qPCR) 和荧光原位杂交测定来评估 LUAD 中的 LINC00987 表达。使用亚硫酸氢盐基因组序列 PCR (BSP) 测定法测定 LINC00987 启动子的甲基化水平。通过免疫沉淀和 RNA Pull-down 测定阐明了 LINC00987 和 SND1 之间的相互作用。通过 CCK-8、EdU、Transwell、流式细胞术和血管生成拟态 (VM) 管形成测定，体外评估了 LINC00987 和 SND1 在 Calu-3 和 NCI-H1688 细胞中的功能意义。 LUAD 中 LINC00987 的表达随着启动子区域的高甲基化而降低，而 LUAD 组织中 LINC00987 启动子的低甲基化与肿瘤进展相关。 5-Aza-CdR 治疗增强了 LINC00987 的表达并抑制了肿瘤生长。从机制上讲，LINC00987 过表达通过与 SND1 直接结合阻碍 LUAD 进展和 VM，从而促进其磷酸化和随后的降解。此外，SND1 的过表达抵消了 LINC00987 下调对体外 LUAD 中细胞增殖、凋亡、细胞迁移、侵袭和 VM 的不利影响。总之，这项开创性研究重点关注 LINC00987 的表达和功能，并揭示 LINC00987 基因的高甲基化可能有助于 LUAD 进展。 LINC00987 通过与 SND1 结合促进其磷酸化和随后的降解，已成为肿瘤发生中潜在的抑癌基因。