肺腺癌（LUAD）是肺癌最常见的组织学亚型。血管生成通过为癌细胞提供氧气和营养，在 LUAD 进展中发挥关键作用。非编码 miR-1293 是 LUAD 组织中显着上调的 miRNA，可作为预测 LUAD 患者预后的新型生物标志物。然而，关于 miR-1293 在 LUAD 进展尤其是癌症诱导的血管生成中的功能的信息很少。在此，我们发现miR-1293敲低可以明显减弱LUAD诱导的体外血管生成，并下调两种最重要的促血管生成细胞因子VEGF-A和bFGF的表达和分泌。事实上，miR-1293 的废除使促进血管生成的 ERK1/2 信号传导失活，其特征是 ERK1/2 磷酸化减少和从细胞核到细胞质的易位。接下来我们发现miR-1293敲低重新激活了内源性ERK1/2通路抑制剂Spry4的表达，并且通过特异性siRNA转染对Spry4进行扰动消除了miR-1293敲低对ERK1/2通路和LUAD诱导的血管生成的抑制。最后，通过体内检测，我们分别发现体内Spry4明显上调，VEGF-A、bFGF、ERK1/2磷酸化，微血管密度标志物CD31表达下调。总的来说，这些结果表明miR-1293敲低可以通过Spry4介导的ERK1/2信号抑制显着减弱LUAD血管生成，这可能有助于揭示miR-1293在LUAD中的更多功能，并为可能的针对miR的LUAD治疗策略提供实验基础。 -1293.版权所有 © 2024。由 Elsevier Inc. 出版。

Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Angiogenesis plays a pivotal role in LUAD progression via supplying oxygen and nutrients for cancer cells. Non-coding miR-1293, a significantly up-regulated miRNA in LUAD tissues, can be potentially used as a novel biomarker for predicting the prognosis of LUAD patients. However, little information is available about the function of miR-1293 in LUAD progression especially cancer-induced angiogenesis. Herein, we found that miR-1293 knockdown could obviously attenuate LUAD-induced angiogenesis in vitro and down-regulate two most important pro-angiogenic cytokines VEGF-A and bFGF expression and secretion. Indeed, miR-1293 abrogation inactivated the angiogenesis-promoting ERK1/2 signaling characterized by decreased ERK1/2 phosphorylation and translocation from nucleus to cytoplasm. Next we found that miR-1293 knockdown reactivated the endogenous ERK1/2 pathway inhibitor Spry4 expression and Spry4 perturbance with specific siRNA transfection abolished the inhibition of ERK1/2 pathway and LUAD-induced angiogenesis by miR-1293 knockdown. Finally, with in vivo assay, we found obvious Spry4 up-regulation and VEGF-A, bFGF, ERK1/2 phosphorylation, micro-vessel density marker CD31 expression down-regulation in vivo, respectively. Collectively, these results indicated that miR-1293 knockdown could significantly attenuate LUAD angiogenesis via Spry4-mediated ERK1/2 signaling inhibition, which might be helpful for uncovering more functions of miR-1293 in LUAD and providing experimental basis for possible LUAD therapeutic strategy targeting miR-1293.Copyright © 2024. Published by Elsevier Inc.