Department of Obstetrics and Gynecology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.
Cancer Biother Radiopharm. 2020 Nov;35(9):640-649. doi: 10.1089/cbr.2019.3318. Epub 2020 Mar 19.
Cervical cancer (CC) is one of the most common cancers among women in the world. Long noncoding RNAs and microRNAs were identified as important regulators in many physiological processes. The objective of this study was to illuminate the mechanism of X-inactive-specific transcript (XIST)/miR-889-3p/Sine oculis homeobox 1 (SIX1) axis in CC. The expression levels of XIST, miR-889-3p, and SIX1 were detected by quantitative real-time polymerase chain reaction. Cell proliferation was assessed by cell counting Kit 8 assay. Cell migration and invasion were evaluated by transwell assay. Cell apoptosis was detected by flow cytometry assay. Murine model was established using transfected Me180 cell. The interaction among XIST, miR-889-3p, and SIX1 was tested by dual-luciferase reporter and RNA immunoprecipitation assays. Protein level of SIX1 was measured by Western blot. XIST was highly expressed in CC tissues and cells. Silenced XIST inhibited proliferation, migration, and invasion and induced apoptosis. Moreover, XIST silencing blocked tumor growth . XIST directly bound to miR-889-3p, and XIST promoted proliferation, migration, and invasion and hindered apoptosis by suppressing miR-889-3p expression. MiR-889-3p targeted SIX1 and negatively regulated SIX1 expression. Furthermore, miR-889-3p had a low expression and SIX1 had a high expression in CC tissues and cells. XIST knockdown reduced SIX1 level by targeting miR-889-3p. In addition, miR-889-3p inhibition abolished the effects of SIX silencing on proliferation, migration, invasion, and apoptosis. XIST knockdown restrained cell proliferation, migration, and invasion and promoted apoptosis by regulating miR-889-3p/SIX1 axis.
宫颈癌（CC）是全球女性中最常见的癌症之一。长非编码 RNA 和 microRNA 被鉴定为许多生理过程中的重要调节因子。本研究旨在阐明 X 失活特异性转录物（XIST）/miR-889-3p/小眼畸形同源盒 1（SIX1）轴在 CC 中的作用机制。通过实时定量聚合酶链反应检测 XIST、miR-889-3p 和 SIX1 的表达水平。通过细胞计数试剂盒 8 测定细胞增殖。通过 Transwell 测定评估细胞迁移和侵袭。通过流式细胞术检测细胞凋亡。使用转染的 Me180 细胞建立小鼠模型。通过双荧光素酶报告和 RNA 免疫沉淀测定检测 XIST、miR-889-3p 和 SIX1 之间的相互作用。通过 Western blot 测定 SIX1 蛋白水平。XIST 在 CC 组织和细胞中高表达。沉默 XIST 抑制增殖、迁移和侵袭并诱导细胞凋亡。此外，XIST 沉默阻断肿瘤生长。XIST 直接与 miR-889-3p 结合，通过抑制 miR-889-3p 的表达，促进增殖、迁移和侵袭并抑制细胞凋亡。miR-889-3p 靶向 SIX1 并负调控 SIX1 表达。此外，miR-889-3p 在 CC 组织和细胞中的表达较低，而 SIX1 表达较高。XIST 敲低通过靶向 miR-889-3p 降低 SIX1 水平。此外，miR-889-3p 抑制消除了 SIX 沉默对增殖、迁移、侵袭和凋亡的影响。XIST 敲低通过调节 miR-889-3p/SIX1 轴抑制细胞增殖、迁移和侵袭并促进细胞凋亡。
