放射治疗广泛应用于宫颈癌患者的治疗，但不可避免地会出现放射抗药性，严重影响治疗效果。众所周知，缺氧在促进肿瘤微环境的放射抗性中发挥着重要作用，但我们对缺氧环境下小细胞外囊泡miRNA对宫颈癌放射敏感性影响的了解仍然有限。从低氧和常氧培养的宫颈癌中提取的小细胞外囊泡评估细胞对放射抗性的影响。通过搜索GEO数据库，发现miR-152-3p是缺氧来源的细胞外囊泡中的潜在效应子。经双荧光素酶报告证实其下游底物为KLF15。通过细胞活性测定检测miR-152-3p和KLF15在调节宫颈癌放射抗性中的作用。这些发现在动物模型体内得到了证实。通过qRT-PCR定量miR-152-3p的表达并评估其预后意义。缺氧环境促进小细胞外囊泡的分泌，并减少辐射引起的细胞凋亡和DNA损伤，同时伴随着小细胞外囊泡表达的增加来自缺氧宫颈癌细胞的 miR-152-3p。此外，小细胞外囊泡 miR-152-3p 促进 Hela 异种移植物生长并降低体内放射敏感性。机制研究表明，KLF15 蛋白是 miR-152-3p 调节放射抗性的下游靶标。我们的研究结果表明，小细胞外囊泡 miR-152-3p 影响放疗的治疗效果，具有作为宫颈癌生物标志物或治疗靶点的潜力预后和改善放射治疗。© 2023。作者。

Radiotherapy is widely used in treating cervical cancer patients, however, radioresistance unavoidably occurs and seriously affects the treatment effect. It is well known that hypoxia plays an important role in promoting radioresistance in tumor microenvironment, yet our understanding of the effect of small extracellular vesicles miRNA on cervical cancer radiosensitivity in hypoxic environment is still limited.Small extracellular vesicles extracted from hypoxic and normoxic cultured cervical cancer cells were evaluated for their effects on radioresistance. miR-152-3p was found to be a potential effector in hypoxia-derived extracellular vesicles by searching the GEO database. Its downstream substrate was confirmed by double luciferase report, which was KLF15. The role of miR-152-3p and KLF15 in regulating cervical cancer radioresistance was detected by cell activity assays. The findings were confirmed in vivo by animal models. The expression of miR-152-3p was quantified by qRT-PCR and its prognostic significance was evaluated.Hypoxic environment promoted the secretion of small extracellular vesicles, and reduced the apoptosis and DNA damage caused by radiation, accompanied by increased expression of small extracellular vesicles miR-152-3p from hypoxic cervical cancer cells. Furthermore, small extracellular vesicles miR-152-3p promoted Hela xenograft growth and reduced the radiosensitivity vivo. Mechanism studies revealed that KLF15 protein was the downstream target of miR-152-3p in regulating radioresistance.Our findings suggest that small extracellular vesicles miR-152-3p affects the therapeutic effect of radiotherapy and holds potential as a biomarker or therapeutic target for cervical cancer prognosis and improving radiotherapy.© 2023. The Author(s).