miR-106a-5p carried by tumor-derived extracellular vesicles promotes the invasion and metastasis of ovarian cancer by targeting KLF6

被引:17
|
作者
Zheng, Yunyun [1 ,2 ]
Zhu, Kang [3 ]
Wang, Guihu [1 ]
机构
[1] Xi An Jiao Tong Univ, Affiliated Hosp 2, Xian 710004, Shaanxi, Peoples R China
[2] Air Force Med Univ, Dept Obstet & Gynecol, Affiliated Hosp AFM 1, Xian 710032, Shaanxi, Peoples R China
[3] Xi An Jiao Tong Univ, Dept Obstet & Gynecol, Affiliated Hosp 2, Xian 710004, Shaanxi, Peoples R China
基金
中国国家自然科学基金;
关键词
Ovarian cancer; Extracellular vesicles; miR-106a-5p; KLF6; PTTG1; Tumor microenvironment; PROGRESSION; ROLES; GENE;
D O I
10.1007/s10585-022-10165-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:603 / 621
页数:19
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