Tumor-suppressor miRNA-27b-5p regulates the growth and metastatic behaviors of ovarian carcinoma cells by targeting CXCL1
Tumor-suppressor miRNA-27b-5p regulates the growth and metastatic behaviors of ovarian carcinoma cells by targeting CXCL1
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DOI：
10.1186/s13048-020-00697-6
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发表时间：
2020-08-11
影响因子：
4
通讯作者：
Hou, Chun Hong
中科院分区：
文献类型：
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作者：
Liu, Chun Hua;Jing, Xue Ning;Hou, Chun Hong
背景MicroRNAs（miRNAs）在卵巢癌的发生发展中起着重要作用。microRNA-27b-5p（miR-27b-5p）是一种与癌症相关的miRNA。然而，miR-27 b-5p的表达谱及其在卵巢癌中的功能尚未研究。方法采用qRT-PCR和western blot检测miR-27 b-5p和C-X-C基序趋化因子配体1（CXCL1）的表达。采用细胞计数试剂盒（CCK-8）、伤口愈合法和Transwell法分别研究miR-27 b-5p对卵巢癌细胞增殖、迁移和侵袭的影响。免疫荧光法检测MMP-2/9的表达。利用生物信息学和荧光素酶报告基因分析技术预测miR-27 b-5p的作用靶点。采用移植瘤模型评价卵巢癌细胞在体内的生长情况。结果miR-27 b-5p在卵巢癌细胞和临床标本中表达下调。卵巢癌患者中miR-27 b-5p的高表达与不利的总生存率相关。miR-27 b-5p的上调可降低SKOV3和OVCAR3细胞的存活率、迁移能力和侵袭能力。miR-27 b-5p对SKOV3细胞的生长也有抑制作用。此外，我们证实了CXCL1是卵巢癌细胞中miR-27 b-5p的靶点。恢复CXCL1的表达可消除miR-27 b-5p对卵巢癌细胞的抑制作用。结论miR-27 b-5p可能通过靶向CXCL1抑制卵巢癌的发生发展。
Background MicroRNAs (miRNAs) play crucial functions in the progression of ovarian cancer. MicroRNA-27b-5p (miR-27b-5p) has been identified as a cancer-associated miRNA. Nevertheless, the expression profile of miR-27b-5p and its functions in ovarian cancer are unexplored. Methods qRT-PCR and western blot analysis were used to detect the levels of miR-27b-5p and C-X-C motif chemokine ligand 1 (CXCL1). The impact of miR-27b-5p on ovarian cancer cells proliferation, migration and invasion in vitro were investigated using Cell Counting Kit-8 (CCK8), wound healing and Transwell, respectively. The expression of matrix metalloprotein-2/9 (MMP-2/9) were measured using immunofluorescence staining. Bioinformatics and luciferase reporter analysis were used to predict the target of miR-27b-5p. The growth of ovarian cancer cells in vivo was evaluated using transplanted tumor model. Results Here, we demonstrated that miR-27b-5p was downregulated in ovarian carcinoma cells and clinical specimens. Higher expression of miR-27b-5p was associated with an unfavorable overall survival in patients with ovarian cancer. Upregulation of miR-27b-5p decreased the viability, migration ability and invasion capacity of SKOV3 and OVCAR3 cell. MiR-27b-5p also inhibited the growth of SKOV3 cell in nude mice. Additionally, we verified that CXCL1 was a target of miR-27b-5p in ovarian carcinoma cells. Restoring the expression of CXCL1 abolished the inhibitory impacts of miR-27b-5p in ovarian cancer carcinoma cells. Conclusion This research revealed that miR-27b-5p restrained the progression of ovarian carcinoma possibly via targeting CXCL1.