Gao Feiying, Wu Qiang, Lu Dan
Medical College of Yangzhou University, Yangzhou, 225009, China.
Key Laboratory of Integrative Medicine in Geriatrics Control of Jiangsu Province, Yangzhou, 225009, China.
Hum Cell. 2024 Jan;37(1):271-284. doi: 10.1007/s13577-023-00987-3. Epub 2023 Sep 28.
Ovarian cancer is the common cause of cancer-related death in women and is considered the most deadly gynecological cancer. It has been established that GATA-binding protein 6 (GATA6) is abnormally expressed in several types of malignant tumors and acts as an oncogenic protein or a tumor suppressor. However, the underlying mechanism of GATA6 in ovarian cancer progression has not been elucidated. Data in the present study revealed that GATA6 expression was negatively correlated to microRNA-10a-5p (miR-10a-5p) in ovarian cancer tissue and cells and that GATA6 is directly targeted by miR-10a-5p. Notably, upregulated miR-10a-5p dramatically inhibited ovarian cancer cell proliferation, tumorigenic ability, migration, and invasion by targeting GATA6. In vitro and in vivo experiments confirmed that miR-10a-5p-mediated downregulation of GATA6 suppressed Akt pathway activation. Overall, our findings suggest that miR-10a-5p could be a novel therapeutic target for ovarian cancer, and targeting the miR-10a-5p/GATA6/Akt axis could improve outcomes in this patient population.
卵巢癌是女性癌症相关死亡的常见原因，被认为是最致命的妇科癌症。已经确定，GATA结合蛋白6（GATA6）在几种类型的恶性肿瘤中异常表达，并作为一种致癌蛋白或肿瘤抑制因子发挥作用。然而，GATA6在卵巢癌进展中的潜在机制尚未阐明。本研究数据显示，在卵巢癌组织和细胞中，GATA6表达与微小RNA-10a-5p（miR-10a-5p）呈负相关，且GATA6是miR-10a-5p的直接靶标。值得注意的是，上调miR-10a-5p通过靶向GATA6显著抑制卵巢癌细胞增殖、致瘤能力、迁移和侵袭。体外和体内实验证实，miR-10a-5p介导的GATA6下调抑制了Akt通路激活。总体而言，我们的研究结果表明，miR-10a-5p可能是卵巢癌的一种新型治疗靶点，靶向miR-10a-5p/GATA6/Akt轴可改善该患者群体的治疗效果。
