Department of Anesthesiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Nephron. 2022;146(5):514-527. doi: 10.1159/000522285. Epub 2022 Mar 18.
Propofol is a commonly used intravenous anesthetic and has been found to perform anticancer effects in many cancers. However, the effects and mechanisms of propofol in clear cell renal cell carcinoma (ccRCC) remain largely undefined.
The expression of circular RNA FBXW7 (circFBXW7) and miR-942 was detected by qRT-PCR. Cell proliferation, apoptosis, migration, and invasion capacities were analyzed using cell counting kit-8, colony formation, flow cytometry, and transwell assays, respectively. Western blot was used to detect the expression levels of PCNA, Cleaved-caspase 3 and MMP protein. The bindings between miR-942 and circFBXW7 were verified using RNA pull-down, dual-luciferase reporter, and RIP assays. Xenograft tumor analysis was employed to detect tumorigenesis in vivo.
Propofol alleviated cell proliferation, migration, invasion, and induced apoptosis in vitro and impeded tumor growth in vivo in ccRCC. Propofol elevated the level of circFBXW7, which knockdown reversed the anticancer effects of propofol on ccRCC cell tumorigenesis. CircFBXW7 directly bound to miR-942, and suppressed ccRCC cell malignant biological behaviors via targeting miR-942. Besides that, propofol decreased miR-942 expression, and miR-942 overexpression attenuated the effects of propofol on ccRCC cells. Moreover, propofol could regulate miR-942 expression through circFBXW7.
Propofol suppressed the growth, migration, and invasion of ccRCC cells by regulating circFBXW7/miR-942 axis, suggesting a potential therapeutic strategy for the intervention of human ccRCC development.
丙泊酚是一种常用的静脉麻醉剂，已在许多癌症中发现具有抗癌作用。然而，丙泊酚在透明细胞肾细胞癌（ccRCC）中的作用和机制在很大程度上仍未确定。
通过 qRT-PCR 检测环状 RNA FBXW7（circFBXW7）和 miR-942 的表达。使用细胞计数试剂盒-8、集落形成、流式细胞术和 Transwell 分析分别分析细胞增殖、凋亡、迁移和侵袭能力。使用 Western blot 检测 PCNA、Cleaved-caspase 3 和 MMP 蛋白的表达水平。使用 RNA 下拉、双荧光素酶报告和 RIP 测定验证 miR-942 和 circFBXW7 之间的结合。使用异种移植肿瘤分析检测体内肿瘤发生。
丙泊酚减轻了 ccRCC 细胞的体外增殖、迁移、侵袭并诱导了凋亡，并阻碍了体内肿瘤的生长。丙泊酚上调 circFBXW7 的水平，其敲低逆转了丙泊酚对 ccRCC 细胞肿瘤发生的抗癌作用。CircFBXW7 直接与 miR-942 结合，并通过靶向 miR-942 抑制 ccRCC 细胞恶性生物学行为。此外，丙泊酚降低了 miR-942 的表达，miR-942 的过表达减弱了丙泊酚对 ccRCC 细胞的作用。此外，丙泊酚可以通过 circFBXW7 调节 miR-942 的表达。
丙泊酚通过调节 circFBXW7/miR-942 轴抑制 ccRCC 细胞的生长、迁移和侵袭，为干预人类 ccRCC 发展提供了一种潜在的治疗策略。
