Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, Shaanxi, China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of AFM (Air Force Medical University), Xi'an, 710032, Shaanxi, China.
Clin Exp Metastasis. 2022 Aug;39(4):603-621. doi: 10.1007/s10585-022-10165-8. Epub 2022 Apr 21.
Tumor-derived extracellular vesicles (EVs) promote ovarian cancer (OC) metastasis by carrying microRNAs (miRs). This study investigated the mechanism of miR-106a-5p carried by OC cell-derived EVs in OC. miR-106a-5p expression in OC tissues and cells was measured. EVs were extracted from SKOV3 cells and normal cells. The internalization of EVs in OC cells was observed. OC cells were treated with SKOV3-EVs or SKOV3-EVs overexpressing miR-106a-5p to detect the proliferation, migration, and invasion. The expression levels of miR-106a-5p, KLF6, and PTTG1 were detected and their binding relationships were identified. Combined experiments were designed to detect the effects of KLF6 and PTTG1 on OC cells. A xenograft tumor experiment was performed to verify the mechanism of EVs-miR-106a-5p and KLF6 in OC metastasis. Consequently, miR-106a-5p was enhanced in OC and correlated with OC metastasis. SKOV3-EVs promoted the proliferation, migration, and invasion of OC cells. Mechanistically, EVs carried miR-106a-5p into other OC cells, inhibited KLF6, reduced the binding of KLF6 to the PTTG1 promoter, and upregulated PTTG1 transcription. Overexpression of KLF6 or silencing of PTTG1 attenuated the promoting effect of EVs-miR-106a-5p on OC cells. EVs-miR-106a-5p facilitated OC metastasis via the KLF6/PTTG1 axis. To conclude, OC cell-derived EVs facilitated the progression and metastasis of OC via the miR-106a-5p/KLF6/PTTG1 axis.
肿瘤细胞外囊泡（EVs）通过携带 microRNAs（miRs）促进卵巢癌（OC）转移。本研究探讨了 OC 细胞来源的 EV 中 miR-106a-5p 在 OC 中的作用机制。检测 OC 组织和细胞中 miR-106a-5p 的表达。从 SKOV3 细胞和正常细胞中提取 EVs。观察 EVs 在 OC 细胞中的内化。用 SKOV3-EVs 或过表达 miR-106a-5p 的 SKOV3-EVs 处理 OC 细胞，检测增殖、迁移和侵袭。检测 miR-106a-5p、KLF6 和 PTTG1 的表达水平，并鉴定其结合关系。设计联合实验检测 KLF6 和 PTTG1 对 OC 细胞的影响。进行异种移植肿瘤实验验证 EVs-miR-106a-5p 和 KLF6 在 OC 转移中的作用机制。结果显示，OC 中 miR-106a-5p 增强，与 OC 转移相关。SKOV3-EVs 促进 OC 细胞的增殖、迁移和侵袭。机制上，EVs 将 miR-106a-5p 带入其他 OC 细胞，抑制 KLF6，减少 KLF6 与 PTTG1 启动子的结合，上调 PTTG1 转录。KLF6 的过表达或 PTTG1 的沉默减弱了 EVs-miR-106a-5p 对 OC 细胞的促进作用。EVs-miR-106a-5p 通过 KLF6/PTTG1 轴促进 OC 转移。综上所述，OC 细胞来源的 EVs 通过 miR-106a-5p/KLF6/PTTG1 轴促进 OC 的进展和转移。
