Gastric cancer (GC) is one of the most leading malignancies. Long noncoding RNA is related to GC. In this study, 11 miRNAs in the exosomes and six lncRNAs in the tissues was examined by qRT-PCR. Correlation analysis was used to analyze the relationship between miRNAs in exosome and lncRNAs in the tissues. Four miRNAs level in GC tissues were examined by qRT-PCR. MTT was used to determine cell viability. Flow cytometry was used to quantify the apoptotic cells. Transwell assay was used to examine the migration and invasion capacity. Dual-luciferase assay was used to examine the interaction between HOTAIR and miR-30a or -b. Capillary formation was used to determine the capillary formation capacity. Weak negative correlations were found between HOTAIR and miR-30a or -b in GC tissue samples. Interestingly, strong negative correlations were identified between the HOTAIR level in GC tissue samples and the miR-30a or -b levels in plasma exosomes. HOTAIR knockdown GC cells exhibited decreased migration, invasion, proliferation, and upregulated apoptosis, which released more miR-30a and -b into the exosomes. KRAS was upregulated when co-cultured with exosomes from HOTAIR overexpressed cells, and promoted GC cells proliferation, migration, and invasion. Meanwhile, HUVEC cells expressed increased VEGF-A and formatted more capillaries. Subsequently, we identified a 10mer target site of miR-30a or -b in HOTAIR sequence, and the overexpression of HOTAIR induced the degradation of miR-30a or -b, indicating a ceRNA role of HOTAIR. We report the negative correlation between the plasma miRNAs level and GC tissue HOTAIR expression for the first time and unveiled the ceRNA role of HOTAIR in GC. HOTAIR functions as an onco-lncRNA regulating the level of miR-30a and -b in both GC cells and exosomes. These findings may give insight into understanding the mechanism of GC pathogenesis and provide new biomarkers for clinical diagnosis.

胃癌（GC）是最主要的恶性肿瘤之一。长链非编码 RNA 与 GC 相关。在这项研究中，通过 qRT-PCR 检测了外泌体中的 11 种 miRNA 和组织中的 6 种 lncRNA。相关分析用于分析外泌体中的miRNA与组织中的lncRNA之间的关系。通过 qRT-PCR 检测了 GC 组织中的四种 miRNAs 水平。MTT用于确定细胞活力。流式细胞术用于量化凋亡细胞。Transwell测定用于检查迁移和侵袭能力。双荧光素酶测定用于检查 HOTAIR 和 miR-30a 或 -b 之间的相互作用。毛细管形成用于确定毛细管形成能力。在 GC 组织样本中发现 HOTAIR 和 miR-30a 或 -b 之间存在弱负相关。有趣的是，在 GC 组织样本中的 HOTAIR 水平与血浆外泌体中的 miR-30a 或 -b 水平之间确定了强烈的负相关。HOTAIR 敲低 GC 细胞表现出减少的迁移、侵袭、增殖和上调的细胞凋亡，这将更多的 miR-30a 和 -b 释放到外泌体中。当与来自 HOTAIR 过表达细胞的外泌体共培养时，KRAS 被上调，并促进 GC 细胞增殖、迁移和侵袭。同时，HUVEC 细胞表达增加的 VEGF-A 并形成更多的毛细血管。随后，我们在 HOTAIR 序列中鉴定了 miR-30a 或 -b 的 10mer 靶位点，HOTAIR 的过表达诱导了 miR-30a 或 -b 的降解，表明 HOTAIR 的 ceRNA 作用。我们首次报告了血浆 miRNA 水平与 GC 组织 HOTAIR 表达之间的负相关，并揭示了 HOTAIR 在 GC 中的 ceRNA 作用。HOTAIR 作为一种 onco-lncRNA 起作用，调节 GC 细胞和外泌体中 miR-30a 和 -b 的水平。这些发现可能有助于深入了解 GC 发病机制，并为临床诊断提供新的生物标志物。