卵巢癌是妇科死亡率最高的恶性肿瘤。我们的目的是鉴定缺氧条件下促进卵巢癌进展和上皮间质转化的新基因。我们筛选了SVIL作为卵巢癌缺氧相关靶点，并探讨了相关分子机制。我们在临床样本和细胞缺氧模型中评估了 SVIL 对卵巢癌进展和转移的影响。进一步，我们研究了SVIL的相关通路，并利用裸鼠原位肿瘤模型证实了SVIL对卵巢癌进展的影响。我们发现SVIL在卵巢癌的缺氧环境中显着高表达，并且SVIL表达与患者存在相关性。 CCK8、伤口愈合试验、Transwell 试验、Western Blot 和细胞凋亡试验表明，敲低 SVIL 可抑制 TGFβ1/smad2/3 通路的激活，从而减弱卵巢癌的进展和上皮间质转化 (EMT)并通过增加顺铂诱导的细胞凋亡来减轻顺铂耐药性。此外，在裸鼠卵巢癌原位模型中，我们发现敲低SVIL可显着抑制肿瘤生长和转移。低氧微环境中高表达的SVIL可通过激活TGFβ1/smad2/3途径增加卵巢癌进展和顺铂耐药。我们的研究表明 SVIL 可能是治疗卵巢癌的新靶点。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Ovarian cancer is the malignant tumor with the highest mortality rate in gynecology. We aimed to identify novel genes that promote ovarian cancer progression and epithelial-mesenchymal transition under hypoxic conditions.We screened SVIL as a hypoxia-associated target in ovarian cancer and explored the related molecular mechanisms. We assessed the effects of SVIL on ovarian cancer progression and metastasis in clinical samples and cellular hypoxia models. Further, we investigated the relevant pathways of SVIL and confirmed the effects of SVIL on ovarian cancer progression by using nude mouse in situ tumor models.We found that SVIL was significantly highly expressed in the hypoxic environment of ovarian cancer, and SVIL expression correlated with patient prognosis.CCK8, Wound-healing assay, Transwell assay, Western Blot, and apoptosis assays revealed that knockdown of SVIL inhibited the activation of the TGFβ1/smad2/3 pathway, which attenuated the progression and epithelial-mesenchymal transition(EMT) of ovarian cancer and alleviated cisplatin resistance by increasing cisplatin-induced apoptosis. Furthermore, in a nude mouse ovarian cancer in situ model, we found that the knockdown of SVIL significantly inhibited tumor growth and metastasis.SVIL highly expressed in the hypoxic microenvironment can increase ovarian cancer progression and cisplatin resistance by activating TGFβ1/smad2/3 pathway. Our study demonstrated that SVIL may be a novel target for the treatment of ovarian cancer.Copyright © 2024 Elsevier Inc. All rights reserved.