lncRNA AC005224.4/miR-140-3p/SNAI2 调节轴通过上皮-间质转化促进卵巢癌的侵袭和转移。
lncRNA AC005224.4/miR-140-3p/SNAI2 regulating axis facilitates the invasion and metastasis of ovarian cancer through epithelial-mesenchymal transition.
发表日期:2023 Mar 21
作者:
Tingchuan Xiong, Yinghong Wang, Yuan Zhang, Jianlin Yuan, Changjun Zhu, Wei Jiang
来源:
CHINESE MEDICAL JOURNAL
摘要:
卵巢癌是全世界女性生殖系统最常见的恶性疾病之一,其中多数卵巢癌病例被诊断为腹腔转移。上皮间充质转化(EMT)在肿瘤细胞转移中发挥着重要作用。但目前还不清楚长链非编码RNA(lncRNA)是否涉及EMT,以及是否影响卵巢癌细胞的浸润和转移。本研究旨在调查lncRNA AC005224.4对卵巢癌的影响。使用实时定量聚合酶链反应(qRT-PCR)测定了卵巢癌和正常卵巢组织中lncRNA AC005224.4、miR-140-3p和蜗牛家族转录抑制因子2(SNAI2)的表达水平。使用Cell Counting Kit-8(CCK-8)和Transwell(迁移和浸润)实验测量了SKOV3和CAOV-3细胞的增殖和转移。使用Western blot检测了E-cadherin、N-cadherin、Snail和Vimentin的含量。使用裸鼠异种移植实验验证了AC005224.4在体内的影响。双荧光素酶报告基因实验确认了miR-140-3p与AC005224.4或SNAI2之间的靶向关系。卵巢癌组织和细胞中观察到了AC005224.4和SNAI2的上调以及miR-140-3p的下调。静默AC005224.4明显减轻了SKOV3和CAOV-3细胞的增殖、迁移、浸润和EMT过程,并在体内抑制了肿瘤发生。miR-140-3p是AC005224.4的靶点,其表达水平受AC005224.4介导下降。miR-140-3p模拟子降低了卵巢癌细胞的增殖、迁移和浸润。SNAI2被确定为miR-140-3p的新靶点,其表达水平可以通过AC005224.4过表达或miR-140-3p沉默来促进。SNAI2的过表达也促进了卵巢癌细胞的生存能力和转移。通过吸附miR-140-3p和促进SNAI2表达,AC005224.4被确认为一个癌基因,有助于更好地理解卵巢癌的发病机制,并为开发针对卵巢癌的新型lncRNA导向治疗提供了线索。版权所有©2023年中国医师协会,由Wolters Kluwer, Inc.根据CC-BY-NC-ND许可证生产。
Ovarian cancer is one of the most widespread malignant diseases of the female reproductive system worldwide. The plurality of ovarian cancer is diagnosed with metastasis in the abdominal cavity. Epithelial-mesenchymal transition (EMT) exerts a vital role in tumor cell metastasis. However, it remains unclear whether long non-coding RNA (lncRNA) are implicated in EMT and influence ovarian cancer cell invasion and metastasis. This study was designed to investigate the impacts of lncRNA AC005224.4 on ovarian cancer.LncRNA AC005224.4, miR-140-3p, and snail family transcriptional repressor 2 (SNAI2) expression levels in ovarian cancer and normal ovarian tissues were determined using real-time quantitative polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) and Transwell (migration and invasion) assays were conducted to measure SKOV3 and CAOV-3 cell proliferation and metastasis. E-cadherin, N-cadherin, Snail, and Vimentin contents were detected using Western blot. Nude mouse xenograft assay was utilized to validate AC005224.4 effects in vivo. Dual-luciferase reporter gene assay confirmed the targeted relationship between miR-140-3p and AC005224.4 or SNAI2.AC005224.4 and SNAI2 upregulation and miR-140-3p downregulation were observed in ovarian cancer tissues and cells. Silencing of AC005224.4 observably moderated SKOV3 and CAOV-3 cell proliferation, migration, invasion, and EMT process in vitro and impaired the tumorigenesis in vivo. miR-140-3p was a target of AC005224.4 and its reduced expression level was mediated by AC005224.4. miR-140-3p mimics decreased the proliferation, migration, and invasion of ovarian cancer cells. SNAI2 was identified as a novel target of miR-140-3p and its expression level was promoted by either AC005224.4 overexpression or miR-140-3p knockdown. Overexpression of SNAI2 also facilitated ovarian cancer cell viability and metastasis.AC005224.4 was confirmed as an oncogene via sponging miR-140-3p and promoted SNAI2 expression, contributing to better understanding of ovarian cancer pathogenesis and shedding light on exploiting the novel lncRNA-directed therapy against ovarian cancer.Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.