环状 RNA circCELSR1 通过海绵吸附 miR-598 来激活 BRD4 信号，从而促进卵巢癌细胞的增殖和转移。
circCELSR1 facilitates ovarian cancer proliferation and metastasis by sponging miR-598 to activate BRD4 signals.
机构信息
Department of Gynecology, the Third Xiangya Hospital of Central South University, No.138 Tongzipo Road, Changsha, 410013, Hunan Province, PR China.
出版信息
Mol Med. 2020 Jul 8;26(1):70. doi: 10.1186/s10020-020-00194-y.
BACKGROUND
Ovarian cancer is one of the most common gynecologic cancers and has high mortality rate due to the lack of early diagnosis method and efficient therapeutic agents. circCELSR1 is up-regulated in ovarian cancer, but its role and mechanisms in ovarian cancer are unclear.
METHODS
Gene expression of circCELSR1, miR-598 and BRD4 in ovarian cells was examined by qRT-PCR. Protein level was determined by Western blotting. Bioinformatic analysis and luciferase assay determined the molecular binding among circCELSR1, miR-598 and BRD4 3' UTR. Cell proliferation, migration, invasion and apoptosis were determined by colony formation, wound healing assay, transwell assay and flow cytometry analysis, respectively. An abdominal cavity metastasis nude mice model was used to determine the in vivo function of circCELSR1.
RESULTS
circCELSR1 and BRD4 were promoted, but miR-598 was suppressed in various ovarian cancer cells. circCELSR1 bound to miR-598 and promoted expression of its downstream target BRD4. Knockdown of circCELSR1 suppressed proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), but promoted apoptosis in ovarian cancer cells, and these effects were reversed by miR-598 inhibition or BRD4 overexpression. circCELSR1 inhibition decreased the expression of BRD4 and its downstream proliferation/migration related genes by targeting miR-598. Furthermore, knockdown of circCELSR1 suppressed ovarian cancer growth and metastasis in nude mice.
CONCLUSION
Knockdown of circCELSR1 inhibited BRD4-mediated proliferation/migration related signaling via sponging miR-598, thereby repressing ovarian cancer progression. This study provides a new regulatory mechanism of ovarian cancer may facilitate the development of therapeutic agents for ovarian cancer.
背景
卵巢癌是最常见的妇科癌症之一，由于缺乏早期诊断方法和有效的治疗药物，死亡率很高。circCELSR1 在卵巢癌中上调，但它在卵巢癌中的作用和机制尚不清楚。
方法
通过 qRT-PCR 检测卵巢细胞中 circCELSR1、miR-598 和 BRD4 的基因表达。通过 Western blot 测定蛋白水平。通过生物信息学分析和荧光素酶报告基因实验确定 circCELSR1、miR-598 和 BRD4 3'UTR 之间的分子结合。通过集落形成、划痕愈合试验、Transwell 试验和流式细胞术分析分别测定细胞增殖、迁移、侵袭和凋亡。使用腹腔转移裸鼠模型测定 circCELSR1 的体内功能。
结果
在各种卵巢癌细胞中，circCELSR1 和 BRD4 被促进，而 miR-598 被抑制。circCELSR1 与 miR-598 结合，并促进其下游靶标 BRD4 的表达。circCELSR1 的敲低抑制了卵巢癌细胞的增殖、迁移、侵袭和上皮-间充质转化（EMT），但促进了凋亡，而 miR-598 抑制或 BRD4 过表达逆转了这些效应。circCELSR1 抑制通过靶向 miR-598 降低 BRD4 及其下游增殖/迁移相关基因的表达。此外，circCELSR1 的敲低抑制了裸鼠卵巢癌的生长和转移。
结论
circCELSR1 的敲低通过海绵 miR-598 抑制 BRD4 介导的增殖/迁移相关信号，从而抑制卵巢癌的进展。本研究为卵巢癌提供了一个新的调控机制，可能有助于开发治疗卵巢癌的药物。
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