Extracellular vesicles derived from cervical cancer cells carrying MCM3AP-AS1 promote angiogenesis and tumor growth in cervical cancer via the miR-93/p21 axis

被引：8
作者：
Mo, Yuzhen [1 ,7 ]
Liang, Zhishan [2 ]
Lan, Liu [3 ]
Xiong, Xifeng [4 ]
Zhang, Cici [5 ]
Liu, Wei [6 ]
Huang, Haowei [1 ]
Fan, Jiangxia [1 ]
Yang, Li [1 ]
机构：
[1] Jinan Univ, Guangzhou Red Cross Hosp, Dept Radiotherapy, Guangzhou 510220, Peoples R China
[2] Peoples Hosp Guangxi Zhuang Autonomous Reg, Dept Cardiol, Nanning 530016, Peoples R China
[3] Guangxi Univ Sci & Technol, Affiliated Hosp 2, Dept Radiotherapy, Liuzhou 545005, Peoples R China
[4] Jinan Univ, Guangzhou Red Cross Hosp, Guangzhou Inst Traumat Surg, Guangzhou 510220, Peoples R China
[5] Jinan Univ, Guangzhou Red Cross Hosp, Dept Radiol, Guangzhou 510220, Peoples R China
[6] Jinan Univ, Guangzhou Red Cross Hosp, Dept Breast Surg, Guangzhou 510220, Peoples R China
[7] Jinan Univ, Guangzhou Red Cross Hosp, Dept Radiotherapy, 396 Tongfu Middle Rd, Guangzhou 510220, Guangdong, Peoples R China
来源：
EXPERIMENTAL CELL RESEARCH | 2023年 / 428卷 / 02期
关键词：
Cervical cancer; Angiogenesis; Extracellular vesicles; MCM3AP-AS1; miR-93; p21; Human umbilical vein vascular endothelial; cells; LONG NONCODING RNA; POTENTIAL BIOMARKERS; PROLIFERATION;
D O I：
10.1016/j.yexcr.2023.113621
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Tumor cells can promote angiogenesis by secreting extracellular vesicles (EVs). Meanwhile, tumor-derived EVs can carry long non-coding RNAs to activate pro-angiogenic signaling in endothelial cells. Here, we investigated the role of long non-coding RNA MCM3AP-AS1 carried by cervical cancer (CC) cell-derived EVs in the angiogenesis and the resultant tumor growth in CC, as well as the potential molecular mechanisms. LncRNAs significantly expressed in CC cell-derived EVs and CC were screened, followed by prediction of downstream target genes. EVs were isolated from HcerEpic and CaSki cell supernatants, followed by identification. The expression of MCM3AP-AS1 in CC was analyzed and its interaction with miR-93-p21 was confirmed. Following co-culture system, the role of MCM3AP-AS1 carried by EVs in HUVEC angiogenic ability, CC cell invasion and migration in vitro along with angiogenesis and tumorigenicity in vivo was assayed. MCM3AP-AS1 was overexpressed in CC cell-derived EVs as well as in CC tissues and cell lines. Cervical cancer cell-derived EVs could transfer MCM3AP-AS1 into HUVECs where MCM3AP-AS1 competitively bound to miR-93 and upregulate the expression of the miR-93 target p21 gene. Thus, MCM3AP-AS1 promoted angiogenesis of HUVECs. In the similar manner, MCM3AP-AS1 enhanced CC cell malignant properties. In nude mice, EVs-MCM3AP-AS1 induced angiogenesis and tumor growth. Overall, this study reveals that CC cell-derived EVs may transport MCM3AP-AS1 to promote angiogenesis and tumor growth in CC.
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页数：11
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